Coherent superpositions of three states for phosphorous donors in silicon prepared using THz radiation.
Superposition of orbital eigenstates is crucial to quantum technology utilizing atoms, such as atomic clocks and quantum computers, and control over the interaction between atoms and their neighbours is an essential ingredient for both gating and readout. The simplest coherent wavefunction control uses a two-eigenstate admixture, but more control over the spatial distribution of the wavefunction can be obtained by increasing the number of states in the wavepacket. Here we demonstrate THz laser pulse control of Si:P orbitals using multiple orbital state admixtures, observing beat patterns produced by Zeeman splitting. The beats are an observable signature of the ability to control the path of the electron, which implies we can now control the strength and duration of the interaction of the atom with different neighbours. This could simplify surface code networks which require spatially controlled interaction between atoms, and we propose an architecture that might take advantage of this.


Identification of the Functions and Prognostic Values of RNA Binding Proteins in Bladder Cancer.
Post-transcriptional regulation plays a leading role in gene regulation and RNA binding proteins (RBPs) are the most important posttranscriptional regulatory protein. RBPs had been found to be abnormally expressed in a variety of tumors and is closely related to its occurrence and progression. However, the exact mechanism of RBPs in bladder cancer (BC) is unknown. We downloaded transcriptomic data of BC from the Cancer Genome Atlas (TCGA) database and used bioinformatics techniques for subsequent analysis. A total of 116 differentially expressed RBPs were selected, among which 61 were up-regulated and 55 were down-regulated. We then identified 12 prognostic RBPs including CTIF, CTU1, DARS2, ENOX1, IGF2BP2, LIN28A, MTG1, NOVA1, PPARGC1B, RBMS3, TDRD1, and ZNF106, and constructed a prognostic risk score model. Based on this model we found that patients in the high-risk group had poorer overall survival (P < 0.001), and the area under the receiver operator characteristic curve for this model was 0.677 for 1 year, 0.697 for 3 years, and 0.709 for 5 years. Next, we drew a nomogram based on the risk score and other clinical variables, which showed better predictive performance. Our findings contribute to a better understanding of the pathogenesis, progression and metastasis of BC. The model of these 12 genes has good predictive value and may have good prospects for improving clinical treatment regimens and patient prognosis.


Effects of Mediterranean diet or mindfulness-based stress reduction on fetal and neonatal brain development: a secondary analysis of a randomized clinical trial.
Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and infant neurodevelopment. This study aimed to investigate if structured lifestyle interventions involving a Mediterranean diet or mindfulness-based stress reduction during pregnancy are associated with differences in fetal and neonatal brain development. This was a secondary analysis of the randomized clinical trial Improving Mothers for a Better Prenatal Care Trial Barcelona that was conducted in Barcelona, Spain, from 2017 to 2020. Participants with singleton pregnancies were randomly allocated into 3 groups, namely Mediterranean diet intervention, stress reduction program, or usual care. Participants in the Mediterranean diet group received monthly individual sessions and free provision of extra-virgin olive oil and walnuts. Pregnant women in the stress reduction group underwent an 8-week mindfulness-based stress reduction program adapted for pregnancy. Magnetic resonance imaging of 90 fetal brains was performed at 36 to 39 weeks of gestation and the Neonatal Neurobehavioral Assessment Scale was completed for 692 newborns at 1 to 3 months. Fetal outcomes were the total brain volume and lobular or regional volumes obtained from a 3-dimensional reconstruction and semiautomatic segmentation of magnetic resonance images. Neonatal outcomes were the 6 clusters scores of the Neonatal Neurobehavioral Assessment Scale. Multiple regression analyses were conducted to assess the association between the interventions and the fetal and neonatal outcomes. When compared with the usual care group, the offspring exposed to a maternal Mediterranean diet had a larger total fetal brain volume (mean, 284.11 cm3; standard deviation, 23.92 cm3 vs 294.01 cm3; standard deviation, 26.29 cm3; P=.04), corpus callosum (mean, 1.16 cm3; standard deviation, 0.19 cm3 vs 1.26 cm3; standard deviation, 0.22 cm3; P=.03), and right frontal lobe (44.20; standard deviation, 4.09 cm3 vs 46.60; standard deviation, 4.69 cm3; P=.02) volumes based on magnetic resonance imaging measures and higher scores in the Neonatal Neurobehavioral Assessment Scale clusters of autonomic stability (mean, 7.4; standard deviation, 0.9 vs 7.6; standard deviation, 0.7; P=.04), social interaction (mean, 7.5; standard deviation, 1.5 vs 7.8; standard deviation, 1.3; P=.03), and range of state (mean, 4.3; standard deviation, 1.3 vs 4.5; standard deviation, 1.0; P=.04). When compared with the usual care group, offspring from the stress reduction group had larger fetal left anterior cingulate gyri volume (1.63; standard deviation, 0.32 m3 vs 1.79; standard deviation, 0.30 cm3; P=.03) based on magnetic resonance imaging and higher scores in the Neonatal Neurobehavioral Assessment Scale for regulation of state (mean, 6.0; standard deviation, 1.8 vs 6.5; standard deviation, 1.5; P<.01). Maternal structured lifestyle interventions involving the promotion of a Mediterranean diet or stress reduction during pregnancy were associated with changes in fetal and neonatal brain development.


Magnetic excitations in Cu6 and Mn6 hexagons embedded in D3d-symmetric polyoxotungstates.
In this article we reconsider the discussion of the magnetic measurements for the two novel polyoxotungstates, (n-BuNH(3))(12)[(CuCl)(6)(AsW(9)O(33))(2)].6H(2)O and (n-BuNH(3))(12)[(MnCl)(6)(SbW(9)O(33))(2)].6H(2)O, which have been synthesized and characterized by Yamase et al. (Inorg.Chem. 2006, 45, 7698). Analysis of the magnetic susceptibility and magnetization for Cu(6)(12+) and Mn(6)(12+) hexagons based on the exact diagonalization of isotropic exchange Hamiltonian shows that the best-fit first-neighbor coupling parameters are J = 35 and 0.55 cm(-1), respectively, while the second-neighbor interactions are very small. These values exceed considerably those obtained by Yamase et al. (J = 8.82 and 0.14 cm(-1)) on the basis of the Kambe-Van Vleck formula that is inappropriate for six-membered rings. We also got perfect fits to the experimental data for the field dependence of magnetization at 1.8 K. The results imply the importance of axial anisotropy, which is shown to be especially pronounced for the Mn(6)(12+) cluster. We discuss also the symmetry assignments of exchange multiplets to the exact SGamma terms (full spin, S, and irreducible representation, Gamma, of the point group) and correlate the results with the selection rules for the anisotropic magnetic contributions. The antisymmetric exchange is shown to appear in orbitally degenerate multiplets as a first-order perturbation and gives rise to an easy axis of magnetization along the C(6) axis. Evaluation of the Zeeman levels shows that the field applied in the plane of the hexagon fully reduces the effect of the antisymmetric exchange.


Epitope of the vaccine-type Bordetella pertussis strain 186 lipooligosaccharide and antiendotoxin activity of antibodies directed against the terminal pentasaccharide-tetanus toxoid conjugate.
Lipooligosaccharides (LOS) isolated from Bordetella pertussis strains 186 and 606 were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high-resolution magic angle spinning nuclear magnetic resonance (NMR). These analyses distinguished between the LOS of strains 186 and 606, suggesting that the structure of LOS in B. pertussis is heterogeneous. The pentasaccharide was selectively cleaved from LOS of B. pertussis strain 186, purified, and covalently linked to a monomer fraction of tetanus toxoid. Injection of rabbits with the neoglycoconjugate emulsified in complete Freund's adjuvant yielded immunoglobulin G antibodies that were reactive with the LOS. These antibodies reacted strongly with B. pertussis LOS possessing the complete dodecasaccharide, as determined by an enzyme-linked immunosorbent assay, immunoblotting, and flow cytometry with intact, live bacterial cells. The binding epitope within the pentasaccharide was investigated by saturation transfer difference (STD) NMR spectroscopy. Protons H-1 and H-4 of the terminal alpha-D-GlcpNAc and proton H-6 and protons of an N-methyl group at H-4 of 3-substituted beta-L-FucpNAc4NMe exhibited the largest saturation transfers. STD NMR experiments confirmed that the immunodominant epitope recognized by the antineoglycoconjugate antibodies is located predominantly in the distal trisaccharide of B. pertussis 186 LOS. The antipentasaccharide antibodies induced by the conjugate inhibited the secretion of tumor necrosis factor alpha, interleukin-6, and NO by LOS-stimulated J774A.1 cells.


Draft genome sequence of Rhodococcus sp. strain P14, a biodegrader of high-molecular-weight polycyclic aromatic hydrocarbons.
The genus Rhodococcus is known for its ability to degrade various xenobiotic compounds. Rhodococcus sp. strain P14 isolated from crude oil-contaminated sediments can degrade mineral oil and polycyclic aromatic hydrocarbons (PAHs). The draft genome sequence of Rhodococcus sp. P14 was obtained using Solexa technology, which provided an invaluable genetic background for further investigation of the ability of P14 to degrade xenobiotic compounds.


Response of nonmidline pain to percutaneous vertebroplasty.
The purpose of this study was to determine the prevalence of nonmidline symptoms in patients undergoing percutaneous vertebroplasty and the response of these symptoms to vertebroplasty. This is a retrospective study performed through examination of patient records, baseline questionnaires, demographic sheets, follow-up questionnaires, reports from telephone follow-up, and pain location diagrams completed before and after percutaneous vertebroplasty. Data were gathered from 350 patient encounters, 686 vertebroplasty procedures, and 288 patients. After determining the prevalence of nonmidline pain, analysis of acquired data was performed to determine the efficacy of vertebroplasty in relieving nonmidline pain. Nonmidline pain was present in 240 of 350 patient encounters. Major symptom areas were the ribs; hip, groin, and buttocks; and legs and thighs. Lesser areas of nonmidline symptoms were the abdomen, shoulders, and waistline. Overall there was improvement in nonmidline pain in 83% of the procedures. Most patients presenting for percutaneous vertebroplasty have nonmidline pain. Vertebroplasty reduced or eliminated nonmidline pain in 76-92% of the patients in whom it was reported. Procedures involving lumbar vertebrae tended to be successful less often than others, but even in these patients the procedure was successful in approximately 75%.


Association Between Polymorphism (5-HTTLPR) of the Serotonin Transporter Gene and Behavioral Response to Unfair Distribution.
Behavioral responses to unfair distribution have been measured mainly using the Ultimatum Game (UG). Recent studies examining the biological basis of behavioral responses to unfair distribution have focused attention on the role of the serotonin transporter gene. However, studies, to date, have been conducted on non-Asians, and it has not been confirmed whether similar results can be seen in other ethnic groups. It has also been shown that behavioral responses to unfair distribution are not only seen in the case of victims themselves but also in the case of third parties not directly affected. This study aimed to determine whether the results of the previous study would be replicated in an Asian population and whether the serotonin transporter gene would also be associated with behavior toward unfair distribution by third parties. We examined the association between polymorphisms (5-HTTLPR) of the serotonin transporter gene and participants' behavior in the UG and the third-party punishment game (TPPG). The results did not show an association between punishment for unfair proposals in the TPPG and genetic polymorphisms, while participants with the SL/LL genotype were more likely to reject unfair offers in the UG than those with the SS genotype. These results indicate that 5-HTTLPR is associated with behavior when unfair intentions are directed at oneself.


Phosphorylated Polyacrylonitrile Fibers as an Efficient and Greener Acetalization Catalyst.
A novel solid acid catalyst (PANEAP F) is developed by immobilization of phosphoric acid on polyacrylonitrile fiber through covalent bonding. Various characterization techniques such as elemental analysis (EA), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), etc. are utilized to confirm the successful grafting and the stability of the fiber catalysts during application. PANEAP F shows high catalytic activity in the acetalization of aldehydes owing to the high utilization efficiency of its functionalized acid sites. In addition, the strong polarity micro-environment in the surface layers of PANEAP F make it highly suitable for catalytic application in both water and alcohol. Furthermore, the fiber catalyst can be applied to the acetalization of aldehydes in a continuous-flow process at room temperature, and shows excellent reactivity and superior recyclability (over 20 times). The many advantages of PANEAP F such as simple preparation, convenient regulation of acid amount, high durability, and eco-friendly process make it very attractive for fixed-bed reactors in the chemical industry.


Lung volumes in tetraplegic patients according to cervical spinal cord injury level.
Fifty-six tetraplegic patients with motor complete lesions (Frankel A and B) underwent spirometric measurements more than 6 months after injury. The results were evaluated according to the level of transection of the cervical cord. A pronounced restrictive respiratory dysfunction was demonstrated in all patients. The expiratory reserve volume (ERV) was zero or markedly reduced in patients at all lesion levels. Systematic increases in both ERV and vital capacity (VC) were found with lower lesion level. The inspiratory capacity (IC) was reduced at all injury levels, but there were no systematic differences in IC between injury levels C4-C8. The total lung capacity (TLC) was reduced and the ratio residual volume/total lung capacity (RV/TLC) was increased in patients at all injury levels. The lung function of patients tested > 12 months after injury was not significantly different from the function in those tested 6-12 months after injury. A respiratory rehabilitation programme for tetraplegic patients should take into account the fact that the respiratory function, especially the forced expiration, is dependent upon injury level.


Hyperparathyroidism.
Hyperparathyroidism is a disease characterized by hypercalcemia with hypophosphoremia resulting from increased secretion of parathyroid hormone (PTH). The disease may be divided into 3 forms: a) primary, b) secondary, c) tertiary (secondary refractory form). Primary hyperparathyroidism is rare in children; hyperplasia is more frequent during the early years of life (neonates and infants) and is difficult to distinguish from adenoma in children. The disease may be asymptomatic; elevated calcemia levels (>12 <13.5 mg/dl) are accompanied by anorexia, asthenia and persistent stipsis; severely elevated concentrations (>13.5 mg/dl) are accompanied by nausea, vomiting, polyuria due to osmosis, with dehydration and progressive onset of lethargy, stupor and coma. Osteopenia or osteitis fibrosa cystica may be present due to augmented bone resorption. Height and weight increases are altered due to anorexia and dehydration. Differential diagnosis includes iatrogenic causes of hypercalcemia (excessive vitamin D intake, prolonged immobilization, etc.) and idiopathic familial hypercalcemia. Emergency treatment is required in cases of extremely elevated hypercalcemia (Ca >13.5-14 mg/dl), due to risk of injury to the heart, the central nervous system, the gastrointestinal tract and the kidneys. The 4 cardinal points of treatment are: hydration, calciuresis, inhibition of bone calcium resorption, treatment of the cause underlying hyperparathyroidism. Secondary hyperparathyroidism is found in cases where chronic hypocalcemia is present, particularly in chronic renal failure, untreated deficiency rickets, chronic intestinal malabsorption, hepatobiliary disease, types I and II vitamin D-dependent rickets, tubular acidosis or Fanconi's syndrome. The tertiary form is distinguished by the autonomous nature of the parathyroid glands which have become hypertrophic/hyperplastic due to uncontrollable, chronic severe renal failure. It can also be of iatrogenic origin due to excessive intake of inorganic phosphates in familial hypophosphatemic rickets or chronic vitamin D deficiency.


In vivo Diagnosis of Primary Cutaneous Amyloidosis -the Role of Reflectance Confocal Microscopy.
Primary cutaneous amyloidosis (PCA) is a form of localized amyloidosis. It is characterized by the deposition of a fibrillar material in the superficial dermis, without affecting other systems or organs. The diagnosis can be made clinically, but usually a skin biopsy is performed in order to exclude other skin diseases with similar appearance. Reflectance confocal microscopy (RCM) is a novel imaging tool that enables in vivo characterization of various skin changes with a high, quasi-microscopic resolution. This technique might have an important role in the differential diagnosis of cutaneous amyloidosis, by the in vivo assessment of epidermal changes and dermal amyloid deposition. Moreover, it is completely non-invasive and can be safely repeated on the same skin area. However, to date, there is only one published paper presenting the confocal features of primary cutaneous amyloidosis. Hereby, we describe the in vivo RCM features of PCA lesions from a patient with diabetes and correlate them with histologic findings. This strengthens the clinical usefulness of in vivo RCM examination for the non-invasive diagnosis of cutaneous amyloidosis, especially in patients that might associate diseases with impaired wound healing.


Philippines: pilot project on HIV and AIDS education and prevention.
The project set up by Christian Children's Fund-Philippines and STOP Trafficking of Filipinos aims to identify cultural practices of young people which may have bearings on their sexual practices and information on how they think and feel about HIV and AIDS. The baseline study found that a number of young adults shared common misconceptions about boy-girl relationships and sex; therefore, there is a need to clarify these concepts and develop self-awareness in order to promote sound and healthy attitudes toward interpersonal relationships and sexual behaviors. The study also found the need for young people to undergo training as a strategy for information dissemination and acquisition of right information and/or expand knowledge to deal effectively with current realities including HIV/AIDS and human sexuality. This baseline information is used to design intervention and communication packages composed of training modules, posters, and other materials that can be used for an educational program for youth. This project was supported by the National AIDS Prevention and Control Program of the Department of Health in the Philippines.


Severity of Subjective Cognitive Complaints and Worries in Older Adults Are Associated With Cerebral Amyloid-β Load.
Subjective cognitive decline (SCD) is considered an early risk stage for dementia due to Alzheimer's disease (AD) and the development of pathological brain changes, such as the aggregation of amyloid-beta (amyloid-β) plaques. This study evaluates the association between specific features of SCD and cerebral amyloid-β load measured by positron emission tomography (PET) with 18F-florbetaben in 40 cognitively normal older individuals. Global amyloid-β, as well as regional amyloid-β load for the frontal, temporal, parietal, and cingulate cortex, was quantified. Specific features of SCD, such as subjective cognitive complaints and worry, were assessed using the 39-item Everyday Cognition Scales and the 16-item Penn State Worry Questionnaire. Spearman's rank partial correlation analyses, adjusted for age and apolipoprotein E ε4 status, were conducted to test the associations between specific features of SCD and cerebral amyloid-β load. The severity of subjective cognitive complaints in everyday memory and organization was positively correlated with amyloid-β load in the frontal cortex. In addition, the severity of subjective cognitive complaints in everyday planning was positively correlated with amyloid-β load in the parietal cortex. Higher levels of worry were associated with higher amyloid-β load in the frontal cortex. After correction of the PET data for partial volume effects, these associations were reduced to trend level. In conclusion, the severity of subjective cognitive complaints and the level of trait worry were positively associated with cortical amyloid-β burden, particularly in the frontal and parietal cortex. Further studies are required to elucidate the direction of these associations in order to develop strategies to prevent amyloid deposition and cognitive decline.


The Use of Modified GFP as a Reporter for Metabolic Activity in Pseudomonas putida.
Many bacteria are now known to enter into a "viable but nonculturable" (VBNC) state in response to various environmental stresses. In this state, the cells are no longer culturable on routine media, but retain viability and in many cases have been shown to be capable of resuscitating to the metabolically active and culturable state. There have been no simple means of measuring the metabolic activity of cells in the VBNC state. The use of green fluorescent protein (GFP) variants with short half-lives was examined in cells intended for environmental release to examine the potential of GFP as a reporter of metabolic activity. Unlike strains with the native (stable) GFP, Pseudomonas putida strains tagged with unstable GFP rapidly lost GFP fluorescence following exposure to starvation and VBNC-inducing conditions. Our results suggest that tagging cells with the modified GFP provides a method for determining metabolic activity in these cells.


[Splenic marginal zone lymphoma. One case report].
Splenic marginal zone lymphoma is very rare B lymphoma, characterized by an indolent clinical course. We report the case of a 68-year-old woman with morphologic and immuno-phenotyping findings consistent with splenic marginal zone lymphoma. The patient had a splenomegaly and pancytopenia. The diagnosis was pathological based on a specimen provided by splenectomy. Two year after surgery, the patient had a normal blood count in the absence of any further treatment.


Alternatives to Nuclear Overhauser Enhancement Spectroscopy Presat and Carr-Purcell-Meiboom-Gill Presat for NMR-Based Metabolomics.
NMR metabolomics are primarily conducted with 1D nuclear Overhauser enhancement spectroscopy (NOESY) presat for water suppression and Carr-Purcell-Meiboom-Gill (CPMG) presat as a T2 filter to remove macromolecule signals. Others pulse sequences exist for these two objectives but are not often used in metabolomics studies, because they are less robust or unknown to the NMR metabolomics community. However, recent improvements on alternative pulse sequences provide attractive alternatives to 1D NOESY presat and CPMG presat. We focus this perspective on PURGE, a water suppression technique, and PROJECT presat, a T2 filter. These two pulse sequences, when optimized, performed at least on par with 1D NOESY presat and CPMG presat, if not better. These pulse sequences were tested on common samples for metabolomics, human plasma, and urine.


Inaccuracy of density functional theory calculations for dihydrogen binding energetics onto Ca cation centers.
We investigate the mechanism of dihydrogen adsorption onto Ca cation centers, which has been the significant focus of recent research for hydrogen storage. We particularly concentrate on reliability of commonly used density-functional theories, in comparison with correlated wave function theories. It is shown that, irrespective of the chosen exchange-correlation potentials, density-functional theories result in unphysical binding of H2 molecules onto Ca1+ system. This suggests that several previous publications could contain a serious overestimation of storage capacity at least in part of their results.


Efficacy and Safety of Sofosbuvir Plus Daclatasvir for Treatment of HCV-Associated Cryoglobulinemia Vasculitis.
Circulating mixed cryoglobulins are detected in 40%-60% of patients with hepatitis C virus (HCV) infection, and overt cryoglobulinemia vasculitis (CryoVas) develops in approximately 15% of patients. Remission of vasculitis has been associated with viral clearance, but few studies have reported the effectiveness of direct-acting antiviral drugs in these patients. We performed an open-label, prospective, multicenter study of the effectiveness and tolerance of an all-oral, interferon- and ribavirin-free regimen of sofosbuvir plus daclatasvir in patients with HCV-associated CryoVas. Forty-one consecutive patients with active HCV-associated CryoVas (median age, 56 y; 53.6% women) were recruited from hospitals in Paris, France, from 2014 through 2016. They received sofosbuvir (400 mg/day) plus daclatasvir (60 mg/day) for 12 weeks (n = 32) or 24 weeks (n = 9), and were evaluated every 4 weeks until week 24 and at week 36. Blood samples were analyzed for complete blood count, serum chemistry profile, level of alanine aminotransferase, rheumatoid factor activity, C4 fraction of complement, and cryoglobulin; peripheral blood mononuclear cells were isolated for flow cytometry analysis. Thirty-seven patients (90.2%) had a complete clinical response (defined by improvement of all the affected organs involved at baseline and no clinical relapse) after a median time of 12 weeks of therapy; all had a sustained virologic response (no detectable serum HCV RNA 12 weeks after the end of antiviral therapy). Patients' mean cryoglobulin level decreased from 0.56 ± 0.18 at baseline to 0.21 ± 0.14 g/L at week 36, and no cryoglobulin was detected in 50% of patients at this time point. After antiviral therapy, patients had increased numbers of T-regulatory cells, IgM+CD21-/low-memory B cells, CD4+CXCR5+ interleukin 21+ cells, and T-helper 17 cells, compared with before therapy. After a median follow-up period of 26 months (interquartile range, 20-30 mo), no patients had a serious adverse event or relapse of vasculitis.


Evaluation of combined radiofrequency and chemical blockade of multi-segmental lumbar sympathetic ganglia in painful diabetic peripheral neuropathy.
Painful diabetic peripheral neuropathy (PDPN) is one of the most common complications of diabetes. PDPN seriously affects the quality of life and is difficult to treat; therefore, there is an urgent need for new cost-effective treatment methods for PDPN. To investigate the efficacy and safety of radiofrequency thermocoagulation (RF) combined with anhydrous ethanol (AE) chemical blockade of lumbar sympathetic ganglia (LSG) in patients with PDPN using computed tomography (CT). Retrospective comparative study. Shengjing Hospital of China Medical University. Ninety patients diagnosed with PDPN were enrolled in this study. The patients were randomly divided into AE group (A, n=30), RF group (B, n=30), and RF+ AE group (C, n=30). The follow-up included preoperative basic conditions, visual analog scale (VAS), the total remission rate (TRR), skin temperature (ST) and the improvement of numbness and hyperalgesia in the lower extremities, complications, and degree of satisfaction (DOS) before and after surgery. Postoperative VASs were significantly decreased compared to preoperative VASs in all groups (P<0.05). The VAS in group A began to increase 3 months (3M) after surgery; VAS scores at 3M, 6 months (6M) and 1 year (1Y) were significantly different compared to group B and C (P<0.05); VAS in group B began to increase after 6M; VAS scores at 6M and 1Y were significantly different compared to group C (P<0.05); Moreover, group C maintained relatively long duration of pain relief. TRR in group A, group B and group C at 1Y after operation was 66.7%, 73.3% and 93.3%, respectively; TRR in group C was statistically different compared to groups A and B (P<0.05). Higher ST in the lower extremities was observed after surgery in all groups compared to peroration (P<0.05); nonetheless, the difference was not statistically significant. The numbness and hyperalgesia improved in all three groups after surgery compared to preoperational time, the numbness in group C was significantly higher compared to groups A and B. In addition, no severe complications were observed. At 6M and 1Y after surgery, the degree of satisfaction in patients from group C was significantly higher compared to groups A and B. Radiofrequency thermocoagulation combined with AE chemical blockade of the LSG was safe and effective. Nevertheless, the details underlying analgesic mechanisms still need to be investigated.


Effects of fasting on bile acid metabolism and biliary lipid composition in man.
The effects of a four to six day fast on gallbladder bile lipid composition, bile acid pool size, bile acid composition, and cholic acid metabolism have been determined in normal human subjects. Total bile acid pool size and cholic acid pool size were measured before and after fasting by a one-sample technique previously validated in our laboratory. The rate of synthesis of cholic acid and its fractional turnover rate before fasting were measured using standard techniques. Estimates of fasting cholic acid synthesis rate and fractional turnover rate were calculated as daily averages from the change in cholic acid pool size, in combination with the change in cholic acid specific activity, during the fasting period. Since these estimates are approximate, a maximum value for cholic acid synthesis rate during fasting was also determined by assuming that the entire change in cholic acid specific activity during the fasting period occurred instantaneously. The molar percent of cholesterol in gallbladder bile was reduced in eight of nine subjects after a four to six day fast (p less than .01; mean reduction 30.5%). The molar percents of bile acid and phospholipid were not significantly altered by fasting. The cholesterol saturation index, calculated on the basis of these data, was reduced by an average of 31.0% after a four to six day fast (p less than .02). The average daily cholic acid synthesis rate and the fractional turnover rate were reduced in all six subjects on whom isotope kinetic studies were carried out. The mean decrease in synthesis rate was 68.5% (p less than .05; range 55.2-79.8%) while the mean decrease in fractional turnover rate was 64.4% (p less than .05; range 30.2-100%). Reduction in synthesis rate was confirmed by the determination of maximum fasting synthesis of cholic acid, which averaged 61.1% lower than synthesis in the fed period. Fasting had no consistent effect on total bile acid pool size, cholic acid pool size, or bile acid species composition.


Broadband etching-free metal grating couplers embedded in titanium dioxide waveguides.
Metal grating couplers embedded into a titanium dioxide layer are proposed. A coupling efficiency better than 20% is experimentally demonstrated with a 3 dB bandwidth of 86 nm which is in agreement with simulation results. This allowed us to perform error-free transmissions of 10 Gbit/s wavelength multiplexed signals in the C-band.


Medicare program; physicians' referrals to health care entities with which they have financial relationships (Phase III). Final rule.
This final rule is the third phase (Phase III) of a final rulemaking amending our regulations regarding the physician self-referral prohibition in section 1877 of the Social Security Act (the Act). Specifically, this rule finalizes, and responds to public comments regarding, the Phase II interim final rule with comment period published on March 26, 2004, which set forth the self-referral prohibition and applicable definitions, interpreted various statutory exceptions to the prohibition, and created additional regulatory exceptions for arrangements that do not pose a risk of program or patient abuse (69 FR 16054). In general, in response to public comments, in this Phase III final rule, we have reduced the regulatory burden on the health care industry through the interpretation of statutory exceptions and modification of the exceptions that were created using the Secretary's discretionary authority under section 1877(b)(4) of the Act to promulgate exceptions for financial relationships that pose no risk of program or patient abuse.


Effect of pioglitazone on the expression of ubiquitin proteasome system and autophagic proteins in rat pancreas with metabolic syndrome.
The metabolic syndrome (MetS) and pathologies associated with metabolic dysregulations a worldwide growing problem. Our previous study demonstrated that pioglitazone (PGZ) has beneficial effects on metabolic syndrome associated disturbances in the heart. However, mechanism mediating the molecular alterations of Ubiquitin proteasome system (UPS) and autophagy has not been investigated in rat pancreas with metabolic syndrome. For this reason, we first aimed to detect whether MetS effects on the expression of UPS (p97/VCP, SVIP, Ubiquitin) and autophagic (p62, LC3) proteins in rat pancreas. The second aim of the study was to find impact of pioglitazone on the expression of UPS and autophagic proteins in MetS rat pancreas. To answer these questions, metabolic syndrome induced rats were used as a model and treated with pioglitazone for 2 weeks. Pancreatic tissue injuries, fibrosis and lipid accumulation were evaluated histopathologically in control, MetS and MetS-PGZ groups. Apoptosis and cell proliferation of pancreatic islet cells were assessed in all groups. UPS and autophagic protein expressions of pancreas in all groups were detected by using immunohistochemistry, double-immunfluorescence and Western blotting. Compared with the controls, the rat fed with high sucrose exhibited signs of metabolic syndrome, such as higher body weight, insulin resistance, higher triglyceride level and hyperglycaemia. MetS rats showed pancreatic tissue degeneration, fibrosis and lipid accumulation when their pancreas were examined with Hematoxilen-eozin and Mallory trichrome staining. Metabolic, histopathologic parameters and cell proliferation showed greater improvement in MetS-PGZ rats and pioglitazone decreased apoptosis of islet cells. Moreover, SVIP, ubiquitin, LC3 and p62 expressions were significantly increased while only p97/VCP expression was significantly decreased in MetS-rat pancreas compared to control. PGZ treatment significantly decreased the MetS-induced increases in autophagy markers. Additionally, UPS and autophagy markers were found to colocalizated with insulin and glucagon. Colocalization ratio of UPS markers with insulin showed significant decrease in MetS rats and PGZ increased this ratio, whereas LC3-insulin colocalization displayed significant increase in MetS rats and PGZ reversed this effect. In conclusion, PGZ improved the pancreatic tissue degeneration by increasing the level of p97/VCP and decreasing autophagic proteins, SVIP and ubiquitin expressions in MetS-rats. Moreover, PGZ has an effect on the colocalization ratio of UPS and autophagy markers with insulin.


Association of circulating active and total ghrelin concentrations with dry matter intake, growth, and carcass characteristics of finishing beef cattle.
Ghrelin is a gut peptide that when acylated is thought to stimulate appetite. Circulating ghrelin concentrations could potentially be used as a predictor of DMI in cattle. The objective of this experiment was to determine the association of circulating ghrelin concentrations with DMI and other production traits. Steers and heifers were fed a finishing diet, and individual intake was recorded for 84 d. Blood samples were collected via jugular venipuncture following the DMI and ADG measurement period. Plasma active ghrelin and total ghrelin were quantified using commercial RIA. Active ghrelin was not correlated to DMI (P=0.36), but when DMI was modeled using a multivariate analysis including plasma metabolites and sex, active ghrelin was shown to be positively associated with DMI (P<0.01) and accounted for 6.2% of the variation accounted for by the regression model (R2=0.33). Total ghrelin was negatively correlated to DMI (P<0.01), but was not significant in a multivariate regression analysis (P=0.13). The ratio of active:total ghrelin was positively associated with DMI (P<0.01) and accounted for 10.2% of the variation in the model (R2=0.35). Active ghrelin was positively associated with ADG (P<0.05), while total ghrelin was negatively associated with ADG (P<0.01), and the ratio of active:total ghrelin was positively associated with ADG (P<0.01). Active ghrelin was not associated with G:F (P=0.88), but total ghrelin concentrations were negatively associated with G:F (P<0.01) and accounted for 10.24% of the variation (R2=0.25). Heifers consumed less feed than steers (P<0.01), tended to have greater active ghrelin concentrations (P=0.06), and had greater total ghrelin concentrations than steers (P=0.04). Total ghrelin concentrations were not different between sire breeds (P=0.80), but active ghrelin concentrations and the ratio of active:total ghrelin differed between breeds (P<0.01), indicating that genetics have an effect on the amount and form of circulating ghrelin. Total ghrelin concentrations tended (P=0.08) to be correlated with HCW, but no other carcass characteristics were correlated with active or total ghrelin concentrations (P>0.10). Results indicated that ghrelin concentrations are associated with DMI in beef cattle and that there is genetic variation that leads to differences in the amount and form of circulating ghrelin which could contribute to variation observed in DMI of beef cattle.


A stitch in time: a cross-sectional survey looking at long lasting insecticide-treated bed net ownership, utilization and attrition in SNNPR, Ethiopia.
Since 2002/03, an estimated 4.7 million nets have been distributed in the Southern Nations, Nationalities and Peoples Region (SNNPR) among an at risk population of approximately 10 million people. Evidence from the region suggests that large-scale net ownership rapidly increased over a relatively short period of time. However, little is known about how coverage is being maintained given that the last mass distribution was in 2006/2007. This study sought to determine the status of current net ownership, utilization and rate of long lasting insecticide-treated nets (LLIN) loss in the previous three years in the context of planning for future net distribution to try to achieve sustainable universal coverage. A total of 750 household respondents were interviewed across malarious, rural kebeles of SNNPR. Households were randomly selected following a two-stage cluster sampling design where kebeles were defined as clusters. Kebeles were chosen using proportional population sampling (PPS), and 25 households within 30 kebeles randomly chosen. Approximately 67.5% (95%CI: 64.1-70.8) of households currently owned at least one net. An estimated 31.0% (95%CI 27.9-34.4) of all nets owned in the previous three years had been discarded by owners, the majority of whom considered the nets too torn, old or dirty (79.9%: 95%CI 75.8-84.0). Households reported that one-third of nets (33.7%) were less than one year old when they were discarded. The majority (58.8%) of currently owned nets had 'good' structural integrity according to a proportionate Hole Index. Nearly two-thirds of households (60.6%) reported using their nets the previous night. The overriding reason for not using nets was that they were too torn (45.7%, 95% CI 39.1-50.7). Yet, few households are making repairs to their nets (3.7%, 95% CI: 2.4-5.1). Results suggest that the life span of nets may be shorter than previously thought, with little maintenance by their owners. With the global move towards malaria elimination it makes sense to aim for sustained high coverage of LLINs. However, in the current economic climate, it also makes sense to hark back to simple tools and messages on the importance of careful net maintenance, which could increase their lifespans.


Gold, Silver, and Palladium Nanoparticles: A Chemical Tool for Biomedical Applications.
Herein, the role of metal-based nanoparticles (NPs) in biomedical analysis and the treatment of critical deceases been highlighted. In the world of nanotechnology, noble elements such as the gold/silver/palladium (Au/Ag/Pd) NPs are the most promising emerging trend to design bioengineering materials that could to be employed as modern diagnostic tools and devices to combat serious diseases. NPs are considered a powerful and advanced chemical tool to diagnose and to cure critical ailments such as HIV, cancer, and other types of infectious illnesses. The treatment of cancer is the most significant application of nanotechnology which is based on premature tumor detection and analysis of cancer cells through Nano-devices. The fascinating characteristic properties of NPs-such as high surface area, high surface Plasmon resonance, multi-functionalization, highly stable nature, and easy processing-make them more prolific for nanotechnology. In this review article, the multifunctional roles of Au/Ag/Pd NPs in the field of medical science, the physicochemical toxicity dependent properties, and the interaction mechanism is highlighted. Due to the cytotoxicity of Ag/Au/Pd NPs, the conclusion and future remarks emphasize the need for further research to minimize the toxicity of NPs in the bio-medicinal field.


Image analysis of stress-induced lignin deposition in Arabidopsis thaliana using the macro program LigninJ for ImageJ software.
In vascular plants, lignin is deposited during morphogenesis but also under stress conditions. Assessing the degree of stress-induced lignin deposition is complicated because it occurs locally and irregularly in plant tissues. In this study, we developed a macro program, LigninJ, for the open-source software ImageJ to automatically and efficiently determine areas and levels of lignification after Wiesner (phloroglucinol-HCl) staining. We used the CIELAB color space for detection of red color following the Wiesner reaction. In addition, LigninJ has a function for adjusting the background level and its white balance to reduce biases that are inherent to individual color images. Furthermore, LigninJ can be used for batch analyses of multiple images, taking about 2 s per image. In this study, we analyzed wound-induced lignin deposition in cotyledons of the Arabidopsis thaliana ecotypes Landsberg erecta and Columbia and assessed ectopic lignin depositions in roots of lignescence (lig) mutants of Arabidopsis. Our results confirmed that this method is efficient for evaluating the degree of stress-induced lignin deposition.


Erythrocyte autoantibodies and expression of CD59 on the surface of red blood cells of polytransfused patients with beta-thalassaemia major.
Repeated transfusions for the treatment of thalassaemia major cause an insult to the patient's immune system and provoke post-transfusion purpura and haemolytic reactions that can be severe and life threatening. This study aims to investigate the presence of erythrocyte autoantibodies and CD59 expression on the surface of red blood cells (RBCs) in patients with beta-thalassaemia major, and any relationship to frequency of blood transfusion. The study looks at a total of 49 patients (both children and adults) with beta-thalassaemia major, divided into four groups according to the number of blood transfusions received and the presence or absence of the spleen. Glycosylated haemoglobin, Coombs' test (direct and indirect) and CD59 level on the RBC surface (by flow cytometry) are estimated in all patients studied. Glycosylated haemoglobin level was significantly lower in those who had received less than 10 units of blood (group III) than in those who had received more than 25 units of blood and had undergone splenectomy (group Ib), and was significantly lower in those who had received 10-25 units of blood (group II) than in those that comprised group Ib (F=3.598, P=0.0205). Considering CD59 expression, there was a marked difference between the groups. Expression was highest in group III and diminished progressively through groups II, Ia (polytransfused, non-splenectomised) and Ib (F=19.83, P=0.0000). No relationship was observed between CD59 expression and either blood group or gender. A significant negative correlation between CD59 expression and reticulocyte percentage (r=-0.538, P=0.000) and normoblast count (r=-0.5455, P=0.000) was found. A negative correlation between lymphocytosis and CD59 expression was also noted in groups III (r=-0.745, P=0.013), Ia (r=-0.5849, P=0.022) and Ib (r=-0.6711, P=0.009). Direct Coombs' test was positive in only one patient in group Ib, who also showed the lowest haemoglobin level. Thalassaemia patients exposed to multiple antigens through repeated blood transfusions showed lower CD59 expression than did those who had received fewer transfused units, which is a good method of detecting potential autoantibodies. Furthermore, a negative Coombs' test does not exclude autoimmunisation in such patients.


In-Utero Low-Dose Irradiation Leads to Persistent Alterations in the Mouse Heart Proteome.
Prenatal exposure to stress such as increased level of reactive oxygen species or antiviral therapy are known factors leading to adult heart defects. The risks following a radiation exposure during fetal period are unknown, as are the mechanisms of any potential cardiac damage. The aim of this study was to gather evidence for possible damage by investigating long-term changes in the mouse heart proteome after prenatal exposure to low and moderate radiation doses. Pregnant C57Bl/6J mice received on embryonic day 11 (E11) a single total body dose of ionizing radiation that ranged from 0.02 Gy to 1.0 Gy. The offspring were sacrificed at the age of 6 months or 2 years. Quantitative proteomic analysis of heart tissue was performed using Isotope Coded Protein Label technology and tandem mass spectrometry. The proteomics data were analyzed by bioinformatics and key changes were validated by immunoblotting. Persistent changes were observed in the expression of proteins representing mitochondrial respiratory complexes, redox and heat shock response, and the cytoskeleton, even at the low dose of 0.1 Gy. The level of total and active form of the kinase MAP4K4 that is essential for the embryonic development of mouse heart was persistently decreased at the radiation dose of 1.0 Gy. This study provides the first insight into the molecular mechanisms of cardiac impairment induced by ionizing radiation exposure during the prenatal period.


Trends in psychotropic medication costs for children and adolescents, 1997-2000.
To examine trends in psychotropic medication utilization and costs for children and adolescents between January 1, 1997, and December 31, 2000. Pharmacy claims were analyzed for mental health users 17 years and younger (N = 83 039) from a national database covering 1.74 million privately insured youths. Utilization rates and costs for dispensed medications were compared across psychotropic drug categories and individual agents over time. Overall use of psychotropic drugs increased from 59.5% of mental health outpatients in 1997 (a 1-year prevalence of 28.7 per 1000) to 62.3% in 2000 (33.7 per 1000), a 4.7% increase. The largest changes in utilization were seen for atypical antipsychotics (138.4%), atypical antidepressants (42.8%), and selective serotonin reuptake inhibitors (18.8%). The average prescription price increased by 17.6% (7.90 US dollars per prescription), a change in turn attributed to a shift toward costlier medications within the same category (55.1% of the increase, or 4.35 US dollars) and to pure inflation (44.9% of the increase, or 3.55 US dollars; P for trend <.001 for all comparisons). Almost half (46.7%) of the 2.7 million US dollars gross sales differential was accounted for by only 3 of the 39 drugs identified (amphetamine compound, risperidone, and sertraline), and 75% was accounted for by 7 drugs (the previous 3 and bupropion, paroxetine, venlafaxine, and citalopram). Psychotropic drug expenditure increases during the late 1990s resulted from more youths being prescribed drugs, a preference for newer and costlier medications, and the net effects of inflation. The impact of managed care and pharmaceutical marketing effects on these trends warrants further study.


Bimetallic Cu-Bi catalysts for efficient electroreduction of CO2 to formate.
Electrochemical CO2 reduction offers an effective means to store renewable electricity in value-added chemical feedstocks. Much effort has been made to develop catalysts that achieve high Faradaic efficiency toward Formate production, but the catalysts still need high operating potentials to drive the CO2-to-formate reduction. Here we report physical vapor deposition to fabricate homogeneously alloyed, compositionally controlled Cu 1-x Bi x bimetallic catalysts over a large area with excellent electrical conductivity. Operating electrochemical studies in Ar-saturated and CO2-saturated electrolytes identified that Cu-Bi catalysts notably suppress the competing H2 evolution reaction and enhance CO2-to-formate selectivity. We reported a formate Faradaic efficiency of >95% at an improved cathodic potential of ∼-0.72 V vs. RHE and a high formate cathodic energy efficiency of ∼70%. The electrochemical reaction is stable over 24 h at a current density of 200 mA cm-2. The work shows the advantages of bimetallic catalysts over single metal catalysts for increased reaction activity and selectivity.


Effect of local administration of platelet-derived growth factor B on functional recovery of peripheral nerve regeneration: A sciatic nerve transection model.
Effects of platelet-derived growth factor B (PDGF-B) on peripheral nerve regeneration was studied using a rat sciatic nerve transection model. Forty-five male, white Wistar rats were divided into three experimental groups (n = 15), randomly: Normal control group (NC), silicon group (SIL), and PDGF-B treated group (SIL/PDGF). In NC group, left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In the SIL group, the left sciatic nerve was exposed in the same way and transected proximal to tibio-peroneal bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted into a silicone conduit and filled with 10 μL phosphate buffered solution. In SIL/PDGF group, the silicon conduit was filled with 10 μL PDGF-B (0.5 ng/mL). Each group was subdivided into three subgroups of five and were studied in 4, 8, 12 weeks after surgery. Behavioral testing, sciatic nerve functional study, gastrocnemius muscle mass, and histomorphometric studies showed earlier regeneration of axons in SIL/PDGF than in SIL group (P < 0.05). Local administration of PDGF-B combined with silicon grafting could accelerate functional recovery and may have clinical implications for the surgical management of patients after facial nerve transection.


Mechanism and kinetics of dark iron redox transformations in previously photolyzed acidic natural organic matter solutions.
Stable organic species produced on irradiation of Suwannee River Fulvic Acid (SRFA) are shown to be important oxidants of Fe(II) in aqueous solutions at acidic pH, with rate constants substantially larger than those for oxygenation of Fe(II) under the same conditions. These Fe(II)-oxidizing species, which are formed during photolysis by superoxide-mediated oxidation of reduced organic moieties that are present intrinsically in SRFA, are long-lived in the dark but prone to rapid oxidation by singlet oxygen ((1)O(2)) under irradiated conditions. The intrinsic reduced organic species are able to reduce Fe(III) at acidic pH. Although the exact identities of the organic Fe(II) oxidant and the organic Fe(III) reductant are unclear, their behavior is consistent with that expected of semiquinone and hydroquinone-like moieties respectively. A kinetic model is developed that adequately describes all aspects of the experimental data obtained, and which is capable of predicting dark Fe(II) oxidation rates and Fe(III) reduction rates in the presence of previously photolyzed natural organic matter.


Ductal carcinoma in situ: recent history and areas of controversy.
The authors provide a perspective on the rapidly evolving field of prognostic analyses designed to quantify the risk of local recurrence in conservatively treated ductal carcinoma in situ (DCIS). These include morphologic features variously defined, nomograms, algorithms and multi-gene expression assays-all of which have completed against the perceived conclusions of the randomized trials of irradiation and Tamoxifen for DCIS: "all subsets benefit". At present the majority of newly diagnosed DCIS can be adequately treated with surgery alone. A number will require irradiation to achieve acceptable local control, and a minority will require mastectomy regardless of adjuvant treatments. Differences in the definition of prognostic factors and in the methods used to establish them is a major reason for the lack of consensus in treatment recommendation.


Early activation of c-Jun N-terminal kinase and p38 kinase regulate cell survival in response to tumor necrosis factor alpha.
Fas ligand and tumor necrosis factor alpha (TNF) bind to members of the TNF receptor superfamily. Stimulation by Fas ligand results in apoptosis, whereas TNF induces multiple effects including proliferation, differentiation, and apoptosis. Activation of the c-Jun N-terminal kinase (JNK) and p38 kinase pathways is common to Fas and TNF signaling; however, their role in apoptosis is controversial. Fas receptor cross-linking induces apoptosis in the absence of actinomycin D and activates JNK in a caspase-dependent manner. In contrast, TNF requires actinomycin D for apoptosis and activates JNK and p38 kinase with biphasic kinetics. The first phase is transient, precedes apoptosis, and is caspase-independent, whereas the second phase is coincident with apoptosis and is caspase-dependent. Inhibition of early TNF-induced JNK and p38 kinases using MKK4/MKK6 mutants or the p38 inhibitor SB203580 increases TNF-induced apoptosis, whereas expression of wild type MKK4/MKK6 enhances survival. In contrast, the Mek inhibitor PD098059 has no effect on survival. These results demonstrate that early activation of p38 kinase (but not Mek) are necessary to protect cells from TNF-mediated cytotoxicity. Thus, early stress kinase activation initiated by TNF plays a key role in regulating apoptosis.


How Activism Features in the Career Lives of Four Generations of Canadian Nurses.
Recent nursing research using a critical feminist lens challenges the prevailing view of political inertia in nursing. This comparative life history study using a critical feminist lens explores the relevance of activism with four generations of Canadian nurses. Purposeful sampling of Ontario nurses resulted in 40 participants who were diverse in terms of generation, practice setting, and activist practice. Interviews and focus groups were completed with the sample of Ontario registered nurses or undergraduate and graduate nursing students: 8 Generation X, 9 Generation Y (Millennials), 20 Boomers, and 3 Overboomers. Factors such as professional norms and personal and organizational supports shaped contradictory nursing activist identities, practices, and impacts. Gendered norms, organizational dynamics, and the political landscape influenced the meanings nurses attributed to critical incidents and influences that prompted activism inside and outside the workplace, shaping the transformative potential of nursing. Despite its limitations, the study has implications for creating professional and organizational supports for consideration of health politics and policy, and spaces for dialogue to support practice and research aligned with social justice goals.


Beam commissioning of the SPring-8 synchrotron.
The beam commissioning of the SPring-8 synchrotron was started in December 1996. In the first ten days, the coarse tuning of the pulse magnets for beam injection from the linac, and the excitation pattern of the dipole and the quadrupole magnets, were accomplished during energy ramping of the beam. The acceleration of the beam up to 8 GeV proceeded smoothly. From January to February 1997, the fine-tuning of the synchrotron was continued and the operating parameters of all of the synchrotron equipment were decided.


Incorporating quality of life measures in HIV clinical trials.
To increase awareness regarding issues specific to health-related quality of life (HRQL) assessments for investigators designing clinical trials and for clinicians reading published reports on clinical trials. HQRL measures are becoming more prevalent, alongside conventional therapeutic and laboratory endpoints. However, they differ from these physiologic or biologic measurements because HRQL data are subjective. We discuss the criteria for selecting and implementing HRQL instruments to optimize the usefulness of HRQL assessments in clinical studies. We conducted a review of selected design and measurement issues that should be considered when planning for the use of HRQL instruments in HIV/AIDS clinical trials. When used appropriately, HRQL measures can indicate the impact of HIV treatment on patient functioning and well-being and can help to inform clinicians about treatment effects.


Does small for gestational age worsen outcomes in gestational diabetics?
Our goal was to determine whether pregnancy outcomes are worse in gestational diabetics with small for gestational age (SGA) than those without. This was a retrospective cohort study of 114 199 pregnancies with gestational diabetes mellitus (GDM) in California, 6446 of which were complicated by SGA. SGA was defined as birth weight < 10th percentile. Predictors included the presence or absence of SGA. Outcomes included respiratory distress syndrome (RDS), neonatal demise (NND), intrauterine fetal demise (IUFD), hypoglycemia and jaundice. The data were also stratified by gestational age looking at 32 + 0-36 + 6 weeks and 37 + 0-41 + 6 weeks. Univariate and multivariate analyses were performed. In the term 37 + 0 to 41 + 6 week GDM cohort the risk of RDS increased from 0.4% to 1.3%, the risk of neonatal demise from 0.02% to 0.09%, the risk of IUFD from 0.1% to 0.4%, the risk of hypoglycemia from 0.4% to 1.0% and the risk of jaundice from 18.0% to 23.3% (p < 0.001 for all). Similar relationships were seen in the 32 + 0 to 36 + 6 week group. The findings remained significant in multivariate analyses. The presence of SGA in a patient with gestational diabetes is associated with significantly increased risks of adverse outcomes compared to gestational diabetics without SGA including increased risks of RDS, neonatal demise, IUFD, hypoglycemia and jaundice.


Graft-versus-host disease and other cutaneous manifestations in pediatric patients transplanted for Fanconi anemia.
The aim of this study was to elaborate a specific protocol for the assessment and early identification of skin lesions in pediatric patients with Fanconi anemia undergoing hematopoietic stem cell transplantation. This is a longitudinal, retrospective, and descriptive study. The medical records of 136 pediatric patients with Fanconi anemia who underwent hematopoietic stem cell transplantation between 2008 and 2018 at the Clinical Hospital of the Federal University of Paraná were reviewed. A specific protocol was created for data collection, which included age, sex, skin color, age at diagnosis of Fanconi anemia, transplantation data, family history of consanguinity, and pre- and post-transplant complications. In addition, the data included the presence of graft-versus-host disease of the skin and other organs, its classification, type of lesion, location, and also skin lesions not related to graft-versus-host disease. Among the skin manifestations in pre-transplant period, café-au-lait spots stood out (32.4%). At least one organ was affected by graft-versus-host disease in 55.1% of patients; the most common involvement being the mouth, followed by the skin. Rash and erythema were the most frequently observed cutaneous manifestations of graft-versus-host disease. A high prevalence of cutaneous manifestations of the disease was observed, as well as cutaneous manifestations of graft-versus-host disease. The protocol developed gathers relevant and standardized information for the follow-up of patients with Fanconi anemia undergoing hematopoietic stem cell transplantation, ensuring greater reliability of the information, and its implementation will allow the prospective evaluation of patients.


Prenatal exposure of rats to nicotine causes persistent alterations of nicotinic cholinergic receptors.
We examined for immediate and persistent changes in nAChRs in cerebral cortex, thalamus and striatum of male rats caused by prenatal exposure to nicotine from gestational day 3 to postnatal day 10 (PN10), and how such exposure affected the responses of adolescents to subsequent nicotine challenge. Receptor numbers were assessed by [(3)H]epibatidine binding and receptor function was measured by acetylcholine-stimulated (86)Rb efflux (cerebral cortex and thalamus) and nicotine-stimulated dopamine release (striatum). Immediate effects of prenatal nicotine, assessed in PN10 animals, were not detected for any parameter. A subsequent 14 day nicotine exposure in adolescence revealed persistent changes caused by prenatal nicotine exposure. Nicotine exposure in adolescents caused up-regulation of binding in all three regions; however, this up-regulation was lost in thalamus from animals prenatally exposed to nicotine. Nicotine exposure in adolescents caused decreased nicotine-stimulated dopamine release in striatum; this effect was lost in animals prenatally exposed to nicotine. Comparison of parameters in PN10 and PN42 rats revealed developmental changes in the CNS cholinergic system. In thalamus, binding increased with age, as did the proportion of (86)Rb efflux with high sensitivity to acetylcholine. In cortex, binding also increased with age, but there was no change in total (86)Rb efflux, and the proportion of high to low sensitivity efflux declined with age. Nicotine-stimulated striatal dopamine release (both total and alpha-conotoxin MII-resistant release) increased with age in naïve animals, but not in those prenatally exposed to nicotine. These findings demonstrate that prenatal exposure to nicotine causes alterations in nAChRs and in their regulation by nicotine that persist into adolescence. These changes may play a role in the increased risk for nicotine addiction observed in adolescent offspring of smoking mothers.


Extending continuous versus discontinuous conditioned stimuli before versus after unconditioned stimuli.
Conditioned suppression was used with rats to study the effects of extending conditioned stimuli (CSs) before versus after the delivery of unconditioned stimuli. These extensions are termed B and A extensions, respectively. Within-group designs were used to compare the effects of extending CSs when 2-min parts of those CSs were separated by temporal gaps of 6 min versus a separation of no gap. The results were as follows: (a) B extensions weakened conditioning more than did A extensions, with or without gaps; (b) under some conditions, this asymmetrical effect persisted with extended training; (c) gaps between 2-min parts of a B extension had no detectable effect; and (d) under some parameter values, gaps between 2-min parts of an A extension weakened conditioning significantly. These results are better predicted by the Sometimes Opponent-Process model (SOP; A. R. Wagner, 1981) than by the Rescorla-Wagner-Frey-Sears real-time model (J. J. B. Ayres, M. Albert, & J. C. Bombace, 1987).


Disturbance Observer-Based Fault-Tolerant Control for Robotic Systems With Guaranteed Prescribed Performance.
The actuator failure compensation control problem of robotic systems possessing dynamic uncertainties has been investigated in this paper. Control design against partial loss of effectiveness (PLOE) and total loss of effectiveness (TLOE) of the actuator are considered and described, respectively, and a disturbance observer (DO) using neural networks is constructed to attenuate the influence of the unknown disturbance. Regarding the prescribed error bounds as time-varying constraints, the control design method based on barrier Lyapunov function (BLF) is used to strictly guarantee both the steady-state performance and the transient performance. A simulation study on a two-link planar manipulator verifies the effectiveness of the proposed controllers in dealing with the prescribed performance, the system uncertainties, and the unknown actuator failure simultaneously. Implementation on a Baxter robot gives an experimental verification of our controller.


Secondary cell walls: biosynthesis, patterned deposition and transcriptional regulation.
Secondary walls are mainly composed of cellulose, hemicelluloses (xylan and glucomannan) and lignin, and are deposited in some specialized cells, such as tracheary elements, fibers and other sclerenchymatous cells. Secondary walls provide strength to these cells, which lend mechanical support and protection to the plant body and, in the case of tracheary elements, enable them to function as conduits for transporting water. Formation of secondary walls is a complex process that requires the co-ordinated expression of secondary wall biosynthetic genes, biosynthesis and targeted secretion of secondary wall components, and patterned deposition and assembly of secondary walls. Here, we provide a comprehensive review of genes involved in secondary wall biosynthesis and deposition. Most of the genes involved in the biosynthesis of secondary wall components, including cellulose, xylan, glucomannan and lignin, have been identified and their co-ordinated activation has been shown to be mediated by a transcriptional network encompassing the secondary wall NAC and MYB master switches and their downstream transcription factors. It has been demonstrated that cortical microtubules and microtubule-associated proteins play important roles in the targeted secretion of cellulose synthase complexes, the oriented deposition of cellulose microfibrils and the patterned deposition of secondary walls. Further investigation of many secondary wall-associated genes with unknown functions will provide new insights into the mechanisms controlling the formation of secondary walls that constitute the bulk of plant biomass.


The foundations of influencing policy and practice: How risk science discourse shaped government action during COVID-19.
COVID-19 demonstrated the complex manner in which discourses from risk science are manipulated to legitimize government action. We use Foucault's theory of Governmentality to explore how a risk science discourse shaped national and local government action during COVID-19. We theorize how national government policymakers and local government risk managers were objectified by (and subjectified themselves to) risk science models, results, and discourses. From this theoretical position we analyze a dataset, including observations of risk science discourse and 22 qualitative interviews, to understand the challenges that national government policymakers, risk scientists, and local government risk managers faced during COVID-19. Findings from our Foucauldian discourse analysis show how, through power and knowledge, competing discourses emerge in a situation that was disturbed by uncertainty-which created disturbed senders (policymakers and risk scientists) and disturbed receivers (risk managers) of risk science. First, we explore the interaction between risk science and policymakers, including how the disturbed context enabled policymakers to select discourse from risk science to justify their policies. This showed government's sociopolitical leveraging of scientific power and knowledge by positioning itself as being submissive to "follow the science." Second, we discuss how risk managers (1) were objectified by the discourse from policymakers that required them to be obedient to risk science, and paradoxically (2) used the disturbed context to justify resisting government objectification through their human agency to subjectify themselves and take action. Using these concepts, we explore the foundation of risk science influence in COVID-19.


High resolution imaging of 2D distribution of lithium in thin samples measured with multipixel detectors in sandwich geometry.
A method that enables visualization of lateral distribution of Li in thin films is described. The method is based on the simultaneous detection of the reaction products of the 6Li(n,α)t nuclear reaction with thermal neutrons measured with two multipixel detectors in a sandwich geometry with a sample. Here, the principle and basic methodological parameters of the method, including tests with thin polymers with known Li microstructure, are discussed.


Genetics, Synergists, and Age Affect Insecticide Sensitivity of the Honey Bee, Apis mellifera.
The number of honey bee colonies in the United States has declined to half of its peak level in the 1940s, and colonies lost over the winter have reached levels that are becoming economically unstable. While the causes of these losses are numerous and the interaction between them is very complex, the role of insecticides has garnered much attention. As a result, there is a need to better understand the risk of insecticides to bees, leading to more studies on both toxicity and exposure. While much research has been conducted on insecticides and bees, there have been very limited studies to elucidate the role that bee genotype and age has on the toxicity of these insecticides. The goal of this study was to determine if there are differences in insecticide sensitivity between honey bees of different genetic backgrounds (Carniolan, Italian, and Russian stocks) and assess if insecticide sensitivity varies with age. We found that Italian bees were the most sensitive of these stocks to insecticides, but variation was largely dependent on the class of insecticide tested. There were almost no differences in organophosphate bioassays between honey bee stocks (<1-fold), moderate differences in pyrethroid bioassays (1.5 to 3-fold), and dramatic differences in neonicotinoid bioassays (3.4 to 33.3-fold). Synergism bioassays with piperonyl butoxide, amitraz, and coumaphos showed increased phenothrin sensitivity in all stocks and also demonstrated further physiological differences between stocks. In addition, as bees aged, the sensitivity to phenothrin significantly decreased, but the sensitivity to naled significantly increased. These results demonstrate the variation arising from the genetic background and physiological transitions in honey bees as they age. This information can be used to determine risk assessment, as well as establishing baseline data for future comparisons to explain the variation in toxicity differences for honey bees reported in the literature.


Computational Analysis of lncRNA from cDNA Sequences.
Based on recent findings, long noncoding (lnc) RNAs represent a potential class of functional molecules within the cell. In this chapter we describe a computational scheme to identify and classify lncRNAs within maize from full-length cDNA sequences to designate subsets of lncRNAs for which biogenesis and regulatory mechanisms may be verified at the bench. We make use of the Coding Potential Calculator and specific Python scripts in our approach.


Health on hold. But Obama legislation would let them live in U.S. legally.
The Obama administration's plan that would give many illegal immigrants a path to stay in the U.S. legally leaves out one thing: federally subsidized access to health insurance coverage. "I think that gives immigrants a mixed message about how welcome they will be," says Sonal Ambegaokar, left, of the National Immigration Law Center.


Chlorosilphanol A and silphanepoxol, labdane diterpenes from Silphium perfoliatum.
Two carterochaetols, chlorosilphanol A and silphanepoxol, isolated from the leaves of Silphium perfoliatum were assigned structures 1 and 3, respectively, from spectral studies and with absolute stereochemistry established by X-ray crystallography of 1. Complete 1H- and 13C-nmr assignments for the parent compounds and their acetates 2 and 4 were made at high-field using 1D and 2D methods, and chlorosilphanol A was chemically converted via its acetate to silphanepoxol. Revision of structure for related carterochaetols in the literature is required, in particular with respect to the stereochemistry at C-12 and that of the side-chain.


Total Syntheses of Uncommon C30 Terpenoids: Chamaecydin and Isochamaecydin.
(-)-Chamaecydin and (-)-isochamaecydin, two uncommon C30 terpenoids comprising abietane-type diterpenes and thujane-type monoterpenes, were achieved from β-pinene with (-)-sabinene in 18 and 20 steps, respectively. Key steps include a Claisen-Ireland rearrangement to establish the all-carbon quaternary center, a Rh catalyzed C-H bond insertion reaction to install a spiro-five-membered ring and a Lewis acid promoted cyclization of polyenes to construct the two six-membered rings.


Impact of COVID-19 vaccination on parental and childhood stress levels in Greece.
The impact of COVID-19 vaccination on parental and childhood stress levels has not been thoroughly investigated. Our aim was to explore the above relationship and identify factors that may influence the dissemination of stress within the family during the pandemic. A cross-sectional e-survey was conducted among a nationwide sample of parents in May 2021 in Greece. Parental stress was assessed using the Perceived Stress Scale (PSS) and the Revised Impact of Event Scale (IES-R) tools. Childhood mental well-being was evaluated with the Children's Revised Impact of Event 13 (CRIES 13) scale. 1,703 unique questionnaires were analyzed; 19.5% of responders were completely vaccinated, 23.7% were partially vaccinated, 38.3% were awaiting vaccination, and 18.5% were classified as vaccine-hesitant (15.2% would delay, and 3.3% refused the vaccination). Stress levels were significantly lower in completely or partially vaccinated parents than in vaccine-hesitant ones (p<0.001 for PSS/IES-R). Vaccination status emerged as a strong and independent predictor of PSS and IES-R. A significant decrease in PSS and IES-R scores was observed in 991 participants between March 2020 and May 2021 (p<0.001 for PSS/IES-R). Vaccine uptake was associated with lower PSS and IES-R scores, irrespective of the phase of the pandemic or other sociodemographic factors. The CRIES 13 score of the participant's children (n=2,969) was 19.4 ±14.9 and positively correlated with the PSS and IES-R scores. Children whose parents were vaccinated had lower stress levels than those of vaccine-hesitant parents (p<0.001). Parental vaccination against COVID-19 is a significant stress and anxiety predictor for both parents and their offspring. Parental and childhood stress levels were correlated, while the effect of vaccination was independent of the pandemic phase. The campaigns to promote vaccine uptake against COVID-19 should also highlight its potential benefit on the psychological well-being of the family.


A survey of routine head CT protocols in Australia.
The choice of scanning protocol in CT will affect the dose delivered to the patient. A nationwide survey of CT operators was carried out in Australia in 1994 to determine the variation in routine head CT protocols. Only 29% of respondents used the supraorbitomeatal (SOM) baseline and thus avoided scanning the eyes. At 74% of sites, the routine protocol included scans both before and after injection of contrast. However, the post-contrast protocol differed from that used in the pre-contrast series in a number of cases. Where 5 mm thick slices were used, the mAs was 16% higher than for 10 mm thick slices. Increased awareness of the influence of baseline, slice thickness/spacing and accompanying exposure factors on patient dose may lead to greater standardization of head CT scanning protocols.


A novel immunogenic cell death signature for the prediction of prognosis and therapies in glioma.
Glioma is a primary cranial malignancy with high recurrence rate, poor prognosis and high mortality. However, the roles of immunogenic cell death (ICD) in glioma remain unclear. Twenty ICD genes were analyzed to be differentially expressed between glioma tissues and non-tumor tissues in 371 glioma patients from The Cancer Genome Atlas (TCGA). Patients were classified into three subgroups via unsupervised clustering. Interestingly, the features of cell-infiltrating from three clusters were matched with three immune phenotypes. An applied scoring system was built depending on the expression of hub ICD-related genes. Notably, the ICD-related score was linked with immune checkpoints and the prognosis of glioma patients. In addition, the applied risk model could be used for the prediction of the effect of chemotherapy and immunotherapy for glioma patients. Furthermore, MYD88 was identified to play key roles in the risk model for glioma patients. MYD88 was specifically expressed in malignant cells and validated to correlate with cell proliferation and invasion. Ligand-receptor pairs are determined as novel communications indicating between immunocytes and malignant cells. Therefore, our research established an ICD-related score to investigate the potential effect to chemotherapy and immunotherapy for glioma patients and indicated that MYD88 was a key role in this risk model.


Nutrient supplementation as adjunct therapy in pulmonary tuberculosis.
The study examined the effect of supplementation with multivitamins and trace elements on microbiological and radiological recovery in patients with pulmonary tuberculosis. Forty-four patients aged 28-50 years were diagnosed with active pulmonary tuberculosis based on X-ray of the chest and smear examination of the sputum for the presence of acid-fast bacilli. They were all treated for six months with a standard anti-tuberculosis regimen that has been found to be effective worldwide for disease control. The subjects were randomized to receive either a multivitamin-trace element supplement or a placebo containing calcium. The two groups were matched on all relevant confounding variables. At two months into the treatment, the group that was supplemented with a multivitamin-trace element preparation showed a significant reduction in the number of individuals with sputum smear positive for acid-fast bacillus: two out of 22 individuals, compared with seven out of 22 among placebo-treated controls (p = 0.028, Fisher's test). It is concluded that patients with tuberculosis should be supplemented with a suitable micronutrient preparation that contains optimum amounts of all vitamins and trace elements that have been documented to enhance the immune response.


Utilization of medium-chain triglycerides by neonatal pigs: effects of emulsification and dose delivered.
Four trials were conducted using 86, 24-h-old pigs to evaluate the utilization of medium-chain triglycerides (MCT). Effects of emulsification and amount of MCT fed were examined. After a 4-h period during which feed was withheld, pigs were force-fed MCT (containing 75% octanoate and 25% decanoate), marking time 0 of the experiment. Blood samples were obtained at 1 and 2 h for subsequent medium-chain fatty acid (MCFA) analysis. In Trials 1 (six pigs/treatment) and 2 (four pigs/treatment) the response to three emulsifying agents was compared to a nonemulsified (NE) control. Twenty milliliters of a 30% (vol/vol) emulsion of MCT or 6 mL of NE MCT was administered. Concentrations of MCFA at 1 h in pigs receiving a Tween 80 (polyoxy-ethylene [20] sorbitan monooleate) emulsion were 3- to 19-fold higher than concentrations in animals administered a gum arabic/gum tragacanth emulsion, a lecithin emulsion, or NE MCT. Trials 3 (eight pigs/treatment) and 4 (six pigs/treatment) were conducted to determine the plasma MCFA concentrations resulting from feeding increasing levels of NE (3, 6, 9, or 12 mL of MCT) or emulsified MCT oil (2, 4, 6, or 8 mL in a 30% Tween 80 emulsion). Plasma octanoate concentrations measured at 1 h increased linearly (P < .05) with increasing MCT dosage through 9 mL of NE and 6 mL of emulsified MCT. A transient narcosis was observed in 8 of 12 animals that received 6 or 8 mL of emulsified MCT and was most pronounced 1 to 2 h after feeding, which roughly corresponded to peak plasma MCFA concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)


Two cases of right atrial myxoma in redo patients. A mere coincidence?
We describe two cases of right atrial myxoma in redo patients who had previously undergone to coronary artery by-pass grafting (CABGs) and mitral valve replacement respectively. Both of patients experienced effort dyspnea and were assessed by trans-thoracic echocardiography, revealing the right atrial masses. They were operated on for myxoma resection and postoperative course was uneventful. Our report deals with the interesting topic of the location of benign masses that are usually more common in the left atrium. Should we hypothesize that the right atrial manipulation during the previous surgery induces the onset of the right atrial mass? It is an interesting matter to debate.


Polymerase chain reaction-mediated characterization of molds belonging to the Aspergillus flavus group and detection of Aspergillus parasiticus in peanut kernels by a multiplex polymerase chain reaction.
The Aspergillus flavus group covers species of A. flavus and Aspergillus parasiticus as aflatoxin producers and Aspergillus oryzae and Aspergillus sojae as koji molds. Genetic similarity among these species is high, and aflatoxin production of a culture may be affected by cultivation conditions and substrate composition. Therefore, a polymerase chain reaction (PCR)-mediated method of detecting the aflatoxin-synthesizing genes to indicate the degree of risk a genotype has of being a phenotypic producer was demonstrated. In this study, 19 strains of the A. flavus group, including A. flavus, A. parasiticus, A. oryzae, A. sojae, and one Aspergillus niger, were subjected to PCR testing in an attempt to detect four genes, encoding for norsolorinic acid reductase (nor-1), versicolorin A dehydrogenase (ver-1), sterigmatocystin O-methyltransferase (omt-1), and a regulatory protein (apa-2), involved in aflatoxin biosynthesis. Concurrently, the strains were cultivated in yeast-malt (YM) broth for aflatoxin detection. Fifteen strains were shown to possess the four target DNA fragments. With regard to aflatoxigenicity, all seven aflatoxigenic strains possessed the four DNA fragments, and five strains bearing less than the four DNA fragments did not produce aflatoxin. When peanut kernels were artificially contaminated with A. parasiticus and A. niger for 7 days, the contaminant DNA was extractable from a piece of cotyledon (ca. 100 mg), and when subjected to multiplex PCR testing using the four pairs of primers coding for the above genes, they were successfully detected. The target DNA fragments were detected in the kernels infected with A. parasiticus, and none was detected in the sound (uninoculated) kernels or in the kernels infected with A. niger.


Structure-metabolism relationships of substituted anilines: prediction of N-acetylation and N-oxanilic acid formation using computational chemistry.
1. The relationship between the in vivo metabolism of substituted anilines, in particular N-acetylation and subsequent formation of oxanilic acids, and their molecular physico-chemical properties has been investigated using computational chemistry and pattern-recognition methods. The methods revealed that the physico-chemical properties most important for N-acetylation and subsequent oxanilic acid formation were electronic descriptors based on partial atomic charges and the susceptibility of the molecules to nucleophilic attack at certain ring positions. 2. The calculated partial atom charge on the amine nitrogen was the parameter most important for predicting that an aniline would be N-acetylated. The calculated nucleophilic susceptibility of the aromatic carbon para to the amino group (NS4) was the most significant parameter for determining oxanilic acid formation following N-acetylation. Thus, highly electron-withdrawing groups substituted at this position gave higher nucleophilic susceptibilities that were related to the presence of an oxanilic acid metabolite. 3. If the parameters relating to N-acetylation were modified by other electron-withdrawing groups in the ring (particularly at the position ortho to the amino group), then acetylation and subsequent oxanilic acid formation did not occur. The introduction of groups that allow the possibility of competing oxidative metabolic pathways elsewhere in the molecule (e.g. CH(3)) also affected the production of oxanilic acids. 4. Using chemometric analysis of the computed physico-chemical properties, the result has been the generation of a model that classifies the metabolism of a number of anilines. This could be used to predict the acetylation and oxanilic formation propensity of a number of substituted anilines whose metabolism was unknown to the system, demonstrating that such techniques may be of use for predicting metabolism and hence could provide support for rational drug design.


Association analyses identify two susceptibility loci 5q31 and 5q22.1 for atopic dermatitis in Chinese Han population.
Atopic dermatitis (AD) and other atopic diseases often share some common genetic and pathogenic bases. Recent genome-wide association studies (GWAS) have identified several loci associated with atopic diseases, allergic sensitization and asthma in different populations. The aim of this study was to investigate whether these susceptibility loci were related to AD in Chinese Han population. Eight single nucleotide polymorphisms (SNPs) from recent atopic diseases and allergic sensitization GWAS were genotyped in 3,013 AD patients and 5,483 healthy controls in Chinese Han population using Sequenom MassArray system. Data was analyzed with PLINK 1.07 software. We identified that the susceptibility loci at 5q31 (RAD50/IL13, rs2158177, P = 1.08×10-3, OR = 1.15) and 5q22.1 (TSLP, rs1837253, P = 2.66×10-3, OR = 0.91) were significantly associated with AD. Genotype-based association testing revealed that the dominant model provided the best fit for both rs2158177 (P = 3.75×10-3) and rs1837253 (P = 5.30×10-3). Pathway analysis conformed that both loci were associated with the JAK-STAT signaling pathway. We identified two susceptibility loci 5q31 and 5q22.1 for AD that might bear candidate genes conferring susceptibility to AD.


Role of Distinct Natural Killer Cell Subsets in Anticancer Response.
Natural killer (NK) cells, the prototypic member of innate lymphoid cells, are important effectors of anticancer immune response. These cells can survey and control tumor initiation due to their capability to recognize and kill malignant cells and to regulate the adaptive immune response via cytokines and chemokines release. However, several studies have shown that tumor-infiltrating NK cells associated with advanced disease can have profound functional defects and display protumor activity. This evidence indicates that NK cell behavior undergoes crucial alterations during cancer progression. Moreover, a further level of complexity is due to the extensive heterogeneity and plasticity of these lymphocytes, implying that different NK cell subsets, endowed with specific phenotypic and functional features, may be involved and play distinct roles in the tumor context. Accordingly, many studies reported the enrichment of selective NK cell subsets within tumor tissue, whereas the underlying mechanisms are not fully elucidated. A malignant microenvironment can significantly impact NK cell activity, by recruiting specific subpopulations and/or influencing their developmental programming or the acquisition of a mature phenotype; in particular, neoplastic, stroma and immune cells, or tumor-derived factors take part in these processes. In this review, we will summarize and discuss the recently acquired knowledge on the possible contribution of distinct NK cell subsets in the control and/or progression of solid and hematological malignancies. Moreover, we will address emerging evidence regarding the role of different components of tumor microenvironment on shaping NK cell response.


Putative pacemakers in the eyestalk and brain of the crayfish Procambarus clarkii show circadian oscillations in levels of mRNA for crustacean hyperglycemic hormone.
Crustacean hyperglycemic hormone (CHH) synthesizing cells in the optic lobe, one of the pacemakers of the circadian system, have been shown to be present in crayfish. However, the presence of CHH in the central brain, another putative pacemaker of the multi-oscillatory circadian system, of this decapod and its circadian transcription in the optic lobe and brain have yet to be explored. Therefore, using qualitative and quantitative PCR, we isolated and cloned a CHH mRNA fragment from two putative pacemakers of the multi-oscillatory circadian system of Procambarus clarkii, the optic lobe and the central brain. This CHH transcript synchronized to daily light-dark cycles and oscillated under dark, constant conditions demonstrating statistically significant daily and circadian rhythms in both structures. Furthermore, to investigate the presence of the peptide in the central brain of this decapod, we used immunohistochemical methods. Confocal microscopy revealed the presence of CHH-IR in fibers and cells of the protocerebral and tritocerebal clusters and neuropiles, particularly in some neurons located in clusters 6, 14, 15 and 17. The presence of CHH positive neurons in structures of P. clarkii where clock proteins have been reported suggests a relationship between the circadian clockwork and CHH. This work provides new insights into the circadian regulation of CHH, a pleiotropic hormone that regulates many physiological processes such as glucose metabolism and osmoregulatory responses to stress.


Using multivariate machine learning methods and structural MRI to classify childhood onset schizophrenia and healthy controls.
Multivariate machine learning methods can be used to classify groups of schizophrenia patients and controls using structural magnetic resonance imaging (MRI). However, machine learning methods to date have not been extended beyond classification and contemporaneously applied in a meaningful way to clinical measures. We hypothesized that brain measures would classify groups, and that increased likelihood of being classified as a patient using regional brain measures would be positively related to illness severity, developmental delays, and genetic risk. Using 74 anatomic brain MRI sub regions and Random Forest (RF), a machine learning method, we classified 98 childhood onset schizophrenia (COS) patients and 99 age, sex, and ethnicity-matched healthy controls. We also used RF to estimate the probability of being classified as a schizophrenia patient based on MRI measures. We then explored relationships between brain-based probability of illness and symptoms, premorbid development, and presence of copy number variation (CNV) associated with schizophrenia. Brain regions jointly classified COS and control groups with 73.7% accuracy. Greater brain-based probability of illness was associated with worse functioning (p = 0.0004) and fewer developmental delays (p = 0.02). Presence of CNV was associated with lower probability of being classified as schizophrenia (p = 0.001). The regions that were most important in classifying groups included left temporal lobes, bilateral dorsolateral prefrontal regions, and left medial parietal lobes. Schizophrenia and control groups can be well classified using RF and anatomic brain measures, and brain-based probability of illness has a positive relationship with illness severity and a negative relationship with developmental delays/problems and CNV-based risk.


Benzimidazole analogs of (L)-tryptophan are substrates and inhibitors of tryptophan indole lyase from Escherichia coli.
Tryptophan indole lyase (TIL), an enzyme found in Escherichia coli and related enterobacteria, produces indole from l-tryptophan (l-Trp). Indole is a signaling molecule in bacteria, affecting biofilm formation, pathogenicity and antibiotic resistance. β-(Benzimidazol-1-yl)-l-alanine (BZI-Ala), 2-amino-4-(benzimidazol-1-yl)butyric acid (homo-BZI-Ala) and 2-amino-5-(benzimidazol-1-yl)pentanoic acid (bishomo-BZI-Ala) were synthesized and tested as substrates and inhibitors of TIL. BZI-Ala is a good substrate of TIL, with Km = 300 μm, kcat = 5.6 s(-1) and kcat /Km = 1.9 × 10(4) , similar to l-Trp. BZI-Ala is also a good substrate for H463F mutant TIL, which has very low activity with l-Trp. In contrast, homo-BZI-Ala was found to be a potent competitive inhibitor of TIL, with a Ki of 13.4 μm. However, the higher homolog, bishomo-BZI-Ala, was inactive as an inhibitor of TIL at a concentration of 600 μm, and is thus a much weaker inhibitor. The reaction of TIL with BZI-Ala was too fast to be observed in the stopped-flow spectrophotometer, and shows an aldimine intermediate in the steady state. However, H463F TIL shows equilibrating mixtures of aldimine and quinonoid complexes in the steady state. The spectra of the reaction of TIL with homo-BZI-Ala show a rapidly formed intermediate absorbing at 340 nm, probably a gem-diamine, that decays slowly to form a quinonoid complex absorbing at 494 nm. The potent binding of homo-BZI-Ala may be due to it being a 'bi-product' analog of the indole-α-aminoacrylate complex. These results demonstrate that an amino acid substrate may be converted to a potent inhibitor of TIL simply by homologation, which may be useful in the design of other potent TIL inhibitors.


Three-dimensional diagnostics and measurements of inertial confinement fusion plasmas.
Recent inertial confinement fusion measurements have highlighted the importance of 3D asymmetry effects on implosion performance. One prominent example is the bulk drift velocity of the deuterium-tritium plasma undergoing fusion ("hotspot"), vHS. Upgrades to the National Ignition Facility neutron time-of-flight diagnostics now provide vHS to better than 1 part in 104 and enable cross correlations with other measurements. This work presents the impact of vHS on the neutron yield, downscatter ratio, apparent ion temperature, electron temperature, and 2D x-ray emission. The necessary improvements to diagnostic suites to take these measurements are also detailed. The benefits of using cross-diagnostic analysis to test hotspot models and theory are discussed, and cross-shot trends are shown.


Breast Cancer Classification through Meta-Learning Ensemble Technique Using Convolution Neural Networks.
This study aims to develop an efficient and accurate breast cancer classification model using meta-learning approaches and multiple convolutional neural networks. This Breast Ultrasound Images (BUSI) dataset contains various types of breast lesions. The goal is to classify these lesions as benign or malignant, which is crucial for the early detection and treatment of breast cancer. The problem is that traditional machine learning and deep learning approaches often fail to accurately classify these images due to their complex and diverse nature. In this research, to address this problem, the proposed model used several advanced techniques, including meta-learning ensemble technique, transfer learning, and data augmentation. Meta-learning will optimize the model's learning process, allowing it to adapt to new and unseen datasets quickly. Transfer learning will leverage the pre-trained models such as Inception, ResNet50, and DenseNet121 to enhance the model's feature extraction ability. Data augmentation techniques will be applied to artificially generate new training images, increasing the size and diversity of the dataset. Meta ensemble learning techniques will combine the outputs of multiple CNNs, improving the model's classification accuracy. The proposed work will be investigated by pre-processing the BUSI dataset first, then training and evaluating multiple CNNs using different architectures and pre-trained models. Then, a meta-learning algorithm will be applied to optimize the learning process, and ensemble learning will be used to combine the outputs of multiple CNN. Additionally, the evaluation results indicate that the model is highly effective with high accuracy. Finally, the proposed model's performance will be compared with state-of-the-art approaches in other existing systems' accuracy, precision, recall, and F1 score.


Mott gap excitations and resonant inelastic x-ray scattering in doped cuprates.
Predictions are made for the momentum- and carrier-dependent degradation of the Mott gap upon doping in high-T(c) cuprates as would be observed in Cu K-edge resonant inelastic x-ray scattering (RIXS). The two-dimensional Hubbard model with second- and third-nearest-neighbor hopping terms has been studied by numerical exact diagonalization. Special emphasis is placed on the particle-hole asymmetry of the Mott gap excitations. We argue that the Mott gap excitations observed by RIXS are significantly influenced by the interaction between charge carriers and antiferromagnetic correlations.