Regeneration from crayfish phasic and tonic motor axons in vitro.
An explant culture system is described that allows examination of axonal growth from the tonically and phasically active motoneurons of the abdominal nerve cord of the crayfish. In this preparation, growth occurs from the cut end of the axon while the remainder of the motoneuron is undisturbed. In vitro growth from the branches of the third roots, which contain the axons from the tonic and phasic motoneurons of abdominal ganglia one through four, was verified as axonal by retrograde labeling of axons and neuronal somata within the nerve cord. Growth from the axons of phasic and tonic cells was observed as early as 24 h after plating and continued for an additional 7-10 days. The morphology and growth rates of the motor terminals differed between the tonic and phasic axons. The phasic axons grew significantly faster and branched more often than did the tonic motor axons. These differences in growth may be related to differences in motoneuron size or, may result from differences in electrical activity. Tonic motoneurons show spontaneous impulse activity for up to 6 days in culture, whereas phasic motoneurons show no spontaneous impulse activity. In addition, the differences in growth may be related to the morphological differences in tonic and phasic motor terminals observed in situ.


Autoimmune epilepsy.
Seizures are a common manifestation of autoimmune limbic encephalitis and multifocal paraneoplastic disorders. Accumulating evidence supports an autoimmune basis for seizures in the absence of syndromic manifestations of encephalitis. The autoimmune epilepsies are immunologically mediated disorders in which recurrent seizures are a primary and persistent clinical feature. When other etiologies have been excluded, an autoimmune etiology is suggested in a patient with epilepsy upon detection of neural autoantibodies and/or the presence of inflammatory changes on cerebrospinal fluid (CSF) or magnetic resonance imaging. In such patients, immunotherapy may be highly effective, depending on the particular autoimmune epilepsy syndrome present. In this chapter, several autoimmune epilepsy syndromes are discussed. First, epilepsies secondary to other primary autoimmune disorders will be discussed, and then those associated with antibodies that are likely to be pathogenic, such as voltage-gated potassium channel-complex and N-methyl-d-aspartate receptor, gamma-aminobutyric acid A and B receptor antibodies. For each syndrome, the typical clinical, imaging, electroencephaloram, CSF, and serologic features, and pathophysiology and treatment are described. Finally, suggested guidelines for the recognition, evaluation, and treatment of autoimmune epilepsy syndromes are provided.


Serotonin-depleted rats are capable of learning in active place avoidance, a spatial task requiring cognitive coordination.
Neurotransmitter substrate of spatial cognition belongs to current topics in behavioral neuroscience. The present study examined the effects of serotonin depletion with p-chlorophenylalanine on learning of rats in active place avoidance, a spatial task requiring allothetic mapping and cognitive coordination and highly dependent upon hippocampus. Serotonin depletion transiently increased locomotor activity in response to footshocks, but it did not change the avoidance efficiency measured by three spatial parameters. These results suggest that serotonin neurotransmission is not crucial for cognitive coordination and allothetic learning, i.e. the processes, which are crucial for active place avoidance performance.


Comparative prognostic accuracy of sepsis scores for hospital mortality in adults with suspected infection in non-ICU and ICU at an academic public hospital.
Sepsis is a global healthcare challenge and reliable tools are needed to identify patients and stratify their risk. Here we compare the prognostic accuracy of the sepsis-related organ failure assessment (SOFA), quick SOFA (qSOFA), systemic inflammatory response syndrome (SIRS), and national early warning system (NEWS) scores for hospital mortality and other outcomes amongst patients with suspected infection at an academic public hospital. 10,981 adult patients with suspected infection hospitalized at a U.S. academic public hospital between 2011-2017 were retrospectively identified. Primary exposures were the maximum SIRS, qSOFA, SOFA, and NEWS scores upon inclusion. Comparative prognostic accuracy for the primary outcome of hospital mortality was assessed using the area under the receiver operating characteristic curve (AUROC). Secondary outcomes included mortality in ICU versus non-ICU settings, ICU transfer, ICU length of stay (LOS) >3 days, and hospital LOS >7 days. Adjusted analyses were performed using a model of baseline risk for hospital mortality. 774 patients (7.1%) died in hospital. Discrimination for hospital mortality was highest for SOFA (AUROC 0.90 [95% CI, 0.89-0.91]), followed by NEWS (AUROC 0.85 [95% CI, 0.84-0.86]), qSOFA (AUROC 0.84 [95% CI, 0.83-0.85]), and SIRS (AUROC 0.79 [95% CI, 0.78-0.81]; p<0.001 for all comparisons). NEWS (AUROC 0.94 [95% CI, 0.93-0.95]) outperformed other scores in predicting ICU transfer (qSOFA AUROC 0.89 [95% CI, 0.87-0.91]; SOFA AUROC, 0.84 [95% CI, 0.82-0.87]; SIRS AUROC 0.81 [95% CI, 0.79-0.83]; p<0.001 for all comparisons). NEWS (AUROC 0.86 [95% CI, 0.85-0.86]) was also superior to other scores in predicting ICU LOS >3 days (SOFA AUROC 0.84 [95% CI, 0.83-0.85; qSOFA AUROC, 0.83 [95% CI, 0.83-0.84]; SIRS AUROC, 0.75 [95% CI, 0.74-0.76]; p<0.002 for all comparisons). Multivariate prediction scores, such as SOFA and NEWS, had greater prognostic accuracy than qSOFA or SIRS for hospital mortality, ICU transfer, and ICU length of stay. Complex sepsis scores may offer enhanced prognostic performance as compared to simple sepsis scores in inpatient hospital settings where more complex scores can be readily calculated.


Osteoporosis: A possible aetiological factor in the development of Scheuermann's disease.
The aim of this study was to test the hypothesis that spinal osteoporosis is an aetiological factor in the development of Scheuermann's disease in adolescents. Clinical and radiological data was collected on 12 individuals with Scheuermann's disease (SD). Lumbar spine bone mineral density (L2-4) was measured using dual energy X-ray absorptiometry. Age and sex-matched adolescents were used as controls. The number of standard deviations from the mean of age and sex-matched controls were calculated. In regards to results, SD patients demonstrated high bone densities of between 1 and 1.5 standard deviations above the mean of age-matched controls. These results suggest that osteoporosis is not an aetiological factor in Scheuermann's disease and that bone density measurements may indeed be higher than aged-matched controls in the general population.


Regulation of parathyroid hormone gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat.
In vivo in the rat 1,25(OH)2D3 decreases and a low calcium increases PTH mRNA levels. We now report the effect of 3 and 8 wk of changes in dietary vitamin D and calcium on PTH mRNA levels. PTH mRNA levels were increased by 3 wk of calcium deficiency (five times), a vitamin D-deficient diet (two times), and combined deficiency (10 times), but not changed by high calcium. Vitamin D-deficient-diet rats' PTH mRNA did not decrease after a single large dose of 1,25(OH)2D3, but did decrease partially after repeated daily doses of 1,25(OH)2D3. Rats after a vitamin D-, calcium-deficient (-D-Ca) diet did not respond to changes in serum calcium at 1 h. Flow cytometry of isolated cells from parathyroid-thyroid tissue separated the smaller parathyroid from the larger thyroid cells and allowed an analysis of parathyroid cell number. In normal vitamin D/normal calcium (NDNCa) rats the parathyroid cells were 24.7 +/- 3.4% (n = 6) of the total cell number, whereas in -D-Ca rats they were 41.8 +/- 6.6% (n = 6) (P less than 0.05). That is, -D-Ca rats had 1.7 times the number of cells, whereas they had 10 times the amount of PTH mRNA, indicating the major contribution (6 times) of increased PTH gene expression per cell. Moreover, a calcium-deficient, more so than a vitamin D-deficient diet, amplifies the expression of the PTH gene, and vitamin D is necessary for an intact response of PTH mRNA to 1,25(OH)2D3 or calcium.


Oxidation-responsive OEGylated poly-L-cysteine and solution properties studies.
The oxidation-responsive behaviors of OEGylated poly-L-cysteine homopolypeptides, that is, poly(L-EG(x)MA-C)n, were investigated. These poly-L-cysteine derivatives adopted mixed conformation in water, in which the β-sheet accounted for a significant proportion. Upon oxidation, the thioethers in polypeptide side chains were converted to polar sulfone groups, which triggered the secondary structure transition from β-sheet preferred conformation to random coil. Accordingly, the increase of side-chain polarity together with conformation changes increased samples' water solubility and cloud point temperature. Using mPEG45-NH2 as macroinitiator, we synthesized PEG45-b-poly(L-EG2MA-C)22 diblock copolymer via ring-opening polymerization (ROP) of L-EG2MA-C N-carboxyanhydride (NCA). The PEG45-b-poly(L-EG2MA-C)22 was able to self-assemble into spherical micelles in aqueous solution, and the micelles could undergo an oxidation-triggered disassembly due to the oxidation-responsive thioethers. Such a new class of oxidation-responsive polypeptides might provide a promising platform to construct inflammation targeting drug delivery systems.


[Analysis of tracheostomy for patients after thoracic esophageal cancer resection].
Tracheostomy is an available method for respiratory management, but a consensus has not been reached with regard to the significance of postoperative respiratory management. So, we analyzed postoperative tracheostomy patients of esophageal cancer and clarified its significance. We analyzed 26 patients from among 85 who underwent resection for thoracic esophageal cancer between April 1989 and December 1992. We divided them into 3 groups according to the indications of tracheostomy, group I: cases with postoperative pulmonary complications (n: 17), group II: cases of prophylaxis against pulmonary complications (n: 5) and group III: cases with dyspnea deriving from postoperative recurrent nerve palsy (n: 4). Tracheostomy was most often performed between 3 and 4 POD in group I, up to 1 POD in group II and from 5 POD to 7 POD in group III. Long-term respiratory support was needed in 13 cases in group I and 2 cases in group II. The rate of tracheostomy was higher in the case who had postoperative recurrent nerve palsy and received preoperative chemoradiotherapy. All cases excluding a case of MOF had a good clinical course after tracheostomy. We were able to clarify the significance of tracheostomy by dividing tracheostomy patients into 3 groups according to the indications for the procedure. It was concluded that tracheostomy is a very useful technique in the respiratory management of resected thoracic esophageal cancer patients.


Alteration of product formation by directed mutagenesis and truncation of the multiple-product sesquiterpene synthases delta-selinene synthase and gamma-humulene synthase.
Two recombinant sesquiterpene synthases from grand fir, delta-selinene synthase and gamma-humulene synthase, each produce more than 30 sesquiterpene olefins from the acyclic precursor farnesyl diphosphate. These enzymes contain a pair of DDxxD motifs, on opposite lips of the presumptive active site, which are thought to be involved in substrate binding and could promote multiple orientations of the substrate alkyl chain from which multiple families of cyclic olefins could derive. Mutagenesis of the first aspartate of either DDxxD motif resulted in depressed k(cat), with lesser effect on K(m), for delta-selinene synthase and afforded a much simpler product spectrum composed largely of monocyclic olefins. Identical alterations in gamma-humulene synthase produced similar kinetic effects with a simplified product spectrum of mostly acyclic and monocyclic olefins. Although impaired in product diversity, none of the mutant synthases lost entirely the capacity to generate complex structures. These results confirm the catalytic significance of the DDxxD motifs and imply that they also influence permitted modes of cyclization. Deletion of an N-terminal arginine pair in delta-selinene synthase (an element potentially involved in substrate isomerization) altered kinetics without substantially altering product outcome. Finally, mutation of an active-site tyrosine residue thought to play a role in proton exchange had little influence; however, substitution of a nearby active site aspartate dramatically altered kinetics and product outcome.


Cathelicidin Insufficiency in Patients with Fatal Leptospirosis.
Leptospirosis causes significant morbidity and mortality worldwide; however, the role of the host immune response in disease progression and high case fatality (>10-50%) is poorly understood. We conducted a multi-parameter investigation of patients with acute leptospirosis to identify mechanisms associated with case fatality. Whole blood transcriptional profiling of 16 hospitalized Brazilian patients with acute leptospirosis (13 survivors, 3 deceased) revealed fatal cases had lower expression of the antimicrobial peptide, cathelicidin, and chemokines, but more abundant pro-inflammatory cytokine receptors. In contrast, survivors generated strong adaptive immune signatures, including transcripts relevant to antigen presentation and immunoglobulin production. In an independent cohort (23 survivors, 22 deceased), fatal cases had higher bacterial loads (P = 0.0004) and lower anti-Leptospira antibody titers (P = 0.02) at the time of hospitalization, independent of the duration of illness. Low serum cathelicidin and RANTES levels during acute illness were independent risk factors for higher bacterial loads (P = 0.005) and death (P = 0.04), respectively. To investigate the mechanism of cathelicidin in patients surviving acute disease, we administered LL-37, the active peptide of cathelicidin, in a hamster model of lethal leptospirosis and found it significantly decreased bacterial loads and increased survival. Our findings indicate that the host immune response plays a central role in severe leptospirosis disease progression. While drawn from a limited study size, significant conclusions include that poor clinical outcomes are associated with high systemic bacterial loads, and a decreased antibody response. Furthermore, our data identified a key role for the antimicrobial peptide, cathelicidin, in mounting an effective bactericidal response against the pathogen, which represents a valuable new therapeutic approach for leptospirosis.


Open reduction and internal fixation of two-part displaced fractures of the greater tuberosity of the proximal part of the humerus.
Twelve patients, ranging in age from thirty-four to seventy-two years (average, fifty-three years), were evaluated an average of five years (range, two to eight years) after open reduction and internal fixation of a two-part displaced fracture of the greater tuberosity of the proximal part of the humerus. The indication for operative reduction was one centimeter or more of displacement of the fracture as seen on the diagnostic radiographs. The anterosuperior deltoid-splitting approach, combined with rotation of the humerus, allowed adequate exposure of the retracted tuberosity. Internal fixation of the greater tuberosity with heavy, non-absorbable sutures and careful repair of the rotator cuff permitted early passive motion. All fractures healed without postoperative displacement. Six patients had an excellent result and six had a good result; active elevation averaged 170 degrees. There was one partial, transient palsy of the axillary nerve.


[Progress of study on relationship between Mcl-1 gene and hematologic malignancies - review].
Mcl-1 (myeloid cell leukemia-1) is a member of Bcl-2 (B cell leukemia-2) family, which may play an important role in cell apoptosis regulation, occurrence and development of tumors. This paper reviews advance of studies on the function of the mcl-1 gene and MCL-1 protein, the signal transduction pathways (JAK/STAT, MAPK, PI-3K) regulating the expression of mcl-1 gene, and the relationship between mcl-1 gene and hematologic malignancies.


The Development of a Magnesium-Releasing and Long-Term Mechanically Stable Calcium Phosphate Bone Cement Possessing Osteogenic and Immunomodulation Effects for Promoting Bone Fracture Regeneration.
Bone grafts are commonly used for the treatment of critical sized bone defects. Since the supply of autologous bone is insufficient, allogeneic bone grafts have been used most of the time. However, the poor osteogenic property of allogeneic bone grafts after pretreatment results in delayed union, non-union, or even occasional deformity. Calcium phosphate cement (CPC) is one of the most promising bone filling materials due to its good biocompatibility and similar chemical components as natural bone. However, clinical applications of CPC were hampered by limited osteogenic effects, undesired immune response which results in resorption, and poor mechanical stability in vivo. Magnesium (Mg) has been proven to trigger bone regeneration through modulating cell behaviors of mesenchymal stem cells and macrophages significantly. Unfortunately, the degradation raters of pure Mg and Mg oxide are extremely fast, resulting in early collapse of Mg contained CPC. In this study, we developed a novel magnesium contained calcium phosphate bone cement (Mg-CPC), possessing long-term mechanical stability and osteogenic effects through sustained release of Mg. Furthermore, in vitro studies showed that Mg-CPC had no cytotoxic effects on hBMMSCs and macrophage RAW 264.7, and could enhance the osteogenic differentiation as determined by alkaline phosphate (ALP) activity and calcium nodule staining, as well as suppress the inflammatory as determined by expression of anti-inflammatory cytokine IL-1RA. We also found that Mg-CPC promoted new bone formation and bone maturation in vivo. These results suggest that Mg-CPC should be a good substitute material for bone grafts in clinical use.


A new miniaturized system for extracorporeal membrane oxygenation in adult respiratory failure.
Mortality of severe acute respiratory distress syndrome in adults is still unacceptably high. Extracorporeal membrane oxygenation (ECMO) could represent an important treatment option, if complications were reduced by new technical developments. Efficiency, side effects and outcome of treatment with a new miniaturized device for veno-venous extracorporeal gas transfer were analysed in 60 consecutive patients with life-threatening respiratory failure. A rapid increase of partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) from 64 (48 to 86) mmHg to 120 (84 to 171) mmHg and a decrease of PaCO2 from 63 (50 to 80) mmHg to 33 (29 to 39) mmHg were observed after start of the extracorporeal support (P < 0.001). Gas exchange capacity of the device averaged 155 (116 to 182) mL/min for oxygen and 210 (164 to 251) mL/min for carbon dioxide. Ventilatory parameters were reduced to a highly protective mode, allowing a fast reduction of tidal volume from 495 (401 to 570) mL to 336 (292 to 404) mL (P < 0.001) and of peak inspiratory pressure from 36 (32 to 40) cmH2O to 31 (28 to 35) cmH2O (P < 0.001). Transfusion requirements averaged 0.8 (0.4 to 1.8) units of red blood cells per day. Sixty-two percent of patients were weaned from the extracorporeal system, and 45% survived to discharge. Veno-venous extracorporeal membrane oxygenation with a new miniaturized device supports gas transfer effectively, allows for highly protective ventilation and is very reliable. Modern ECMO technology extends treatment opportunities in severe lung failure.


Highly Stable Lithium/Sodium Metal Batteries with High Utilization Enabled by a Holey Two-Dimensional N-Doped TiNb2O7 Host.
Lithium/sodium metal batteries have attracted enormous attention as promising candidates for high-energy storage devices. However, their practical applications are impeded by the growth of dendrites upon Li/Na plating. Here, we report that holey 2D N-doped TiNb2O7 (N-TNO) nanosheets with high electroactive surface area and large amounts of lithiophilic/sodiophilic sites can effectively regulate Li/Na deposition as an interfacial layer, leading to an excellent cycling stability. The N-TNO interfacial layer enables the Li||Li symmetric cell to sustain stable electrodeposition over 1000 h as well as the Na||Na cell to stably cycle for 2400 h at 1 mA cm-2 and 3 mA h cm-2 with a depth of discharge as high as 50%. The full cells of the Li/Na anodes based on the N-TNO layer paired with the LiFePO4 and NaTi2(PO4)3 cathodes, respectively, show a very stable cycling over 1000 cycles at a negative-to-positive electrode capacity (N/P) ratio up to 3.


Genetic analysis of morphological traits in spring wheat from the Northeast of China by a genome-wide association study.
Identification of the gene for agronomic traits is important for the wheat marker-assisted selection (MAS) breeding. To identify the new and stable loci for agronomic traits, including flag leaf length (FLL), flag leaf width (FLW), uppermost internode length (UIL), and plant morphology (PM, including prostrate, semi-prostrate, and erect). A total of 251 spring wheat accessions collected from the Northeast of China were used to conduct genome-wide association study (GWAS) by 55K SNP arrays. A total of 30 loci for morphological traits were detected, and each explained 4.8-17.9% of the phenotypic variations. Of these, 13 loci have been reported by previous studies, and the other 17 are novel. We have identified seven genes involved in the signal transduction, cell-cycle progression, and plant development pathway as candidate genes. This study provides new insights into the genetic basis of morphological traits. The associated SNPs and accessions with more of favorable alleles identified in this study could be used to promote the wheat breeding progresses.


Acetate formation in the photoheterotrophic bacterium Chloroflexus aurantiacus involves an archaeal type ADP-forming acetyl-CoA synthetase isoenzyme I.
The bacterium Chloroflexus aurantiacus excreted significant amounts of acetate during photohetero trophic growth on glucose and in resting cell suspensions. Up to 1.5 mol acetate per mol glucose were formed. In acetate-forming cells, the activities of phosphotransacetylase and acetate kinase, usually involved in acetate formation in Bacteria, could not be detected; instead, the cells contained an acetyl-CoA synthetase (ADP-forming) (ACD) (acetyl-CoA + ADP + Pi → acetate + ATP + CoA), an enzyme so far reported in prokaryotes to be specific for acetate-forming Archaea. ACD, which was induced 10-fold during growth on glucose, was purified and the encoding gene was identified as Caur_3920. The recombinant enzyme, a homotetrameric 300-kDa protein composed of 75-kDa subunits, was characterized as functional ACD. Substrate specificities and kinetic constants for acetyl-CoA/acetate and other acyl-CoA esters/acids were determined, showing similarity of the C. aurantiacus ACD to archaeal ACD I isoenzymes, which are involved in acetate formation from sugars. This is the first report of a functional ACD involved in acetate formation in the domain of Bacteria.


Interferon-alpha and ribavirin treatment in patients with hepatitis C virus-related systemic vasculitis.
Hepatitis C virus (HCV)-related vasculitis may involve multiple organs, including the skin, kidneys, and nervous system, and may be life-threatening. Although HCV is increasingly recognized as a cause of systemic vasculitis, limited data are available regarding the optimal treatment of this potentially serious condition. Therefore, we retrospectively analyzed the response to treatment in patients with chronic hepatitis C complicated by systemic vasculitis who had received antiviral therapy with interferon-alpha (IFNalpha) and ribavirin. This retrospective study included 27 patients with systemic vasculitis and chronic HCV infection. Each patient had received treatment with IFNalpha and ribavirin for at least 6 months. The response to antiviral treatment was analyzed by comparing clinical, immunologic, and virologic data at the time of entry and during followup. Clinical response was defined according to the evolution of weight, arthralgia, nervous system, renal system, and cutaneous involvement. The virologic and immunologic responses were defined by the absence of HCV RNA and the absence of cryoglobulinemia, respectively, both 6 months after stopping antiviral therapy and at the end of followup. Patients received IFNalpha for a mean +/- SD of 20 +/- 14 months and ribavirin (at a mean +/- SD dosage of 895 +/- 250 mg/day) for 14 +/- 12 months. Other treatments included low-dose corticosteroids and plasma exchange. After a mean +/- SD followup of 57 +/- 29 months, 25 of 27 patients are alive and are being followed up as outpatients. Because of the heterogeneity of anti-HCV treatments received, the main results were stratified according to patients with 6 months of followup after stopping antiviral treatment (group 1, n = 14) and those who were still undergoing antiviral therapy at the time of analysis (group 2, n = 13). Nine patients in group 1 had a sustained virologic response and were clinical and immunologic complete responders. Four patients in group 1 were virologic nonresponders, and 3 of these patients had partial clinical and immunologic responses. Overall, 10 patients in group 1 had a complete clinical and immunologic response of their vasculitis (all 9 of the sustained virologic responders and 1 of the 5 patients who remained viremic). At the end of followup, 7 patients in group 2 were negative for HCV RNA; 6 were complete clinical responders. Among the other 6 patients in group 2, who had persistent viremia, 4 had a partial clinical response. Among the patients in group 1, HCV RNA was more often undetectable and genotype 1 was less frequent in complete clinical responders compared with partial/nonresponders. Age, sex, clinical vasculitic involvement, mean duration or total cumulative dose of IFNalpha or ribavirin, and use of steroids or plasmapheresis did not differ significantly according to clinical response. Treatment with IFNalpha and ribavirin can achieve a complete clinical response in most patients with HCV-related systemic vasculitis. Complete clinical response correlates with the eradication of HCV.


Toward evidence-based prescribing at end of life: a comparative analysis of sustained-release morphine, oxycodone, and transdermal fentanyl, with pain, constipation, and caregiver interaction outcomes in hospice patients.
The primary goal of this investigation was to examine selected outcomes in hospice patients who are prescribed one of three sustained-release opioid preparations. The outcomes examined include: pain score, constipation severity, and ability of the patient to communicate with caregivers. This study included 12,000 terminally ill patients consecutively admitted to hospices and receiving pharmaceutical care services between the period of July 1 and December 31, 2002. We retrospectively examined prescribing patterns of sustained-release morphine, oxycodone, and transdermal fentanyl. We compared individual opioids on the aforementioned outcome markers, as well as patient gender, terminal diagnosis, and median length of stay. Patients prescribed a sustained-release opioid had similar average ratings of pain and constipation severity, regardless of the agent chosen. Patients prescribed transdermal fentanyl were reported to have more difficulty communicating with friends and family when compared with patients prescribed either morphine or oxycodone. On average, patients prescribed transdermal fentanyl had a shorter length of stay on hospice as compared with those receiving morphine or oxycodone. There was no difference in observed pain or constipation severity among patients prescribed sustained-release opioid preparations. Patients receiving fentanyl were likely to have been prescribed the medication due to advanced illness and associated dysphagia. Diminished ability to communicate with caregivers and a shorter hospice course would be consistent with this profile. Further investigation is warranted to examine the correlation between a patient's ability to interact with caregivers and pain control achieved.


Association among sleep, depression, and health-related quality of life in patients with non-dialysis chronic kidney disease during the coronavirus disease 2019 pandemic.
Sleep disturbance is well documented as a crucial element that impairs health. Depression and health-related quality of life (HRQOL), which on behalf of a patient's overall perception of emotional, physical and social well-being, are increasingly emphasized self-reported health outcomes especially during the coronavirus disease 2019 (COVID-19) pandemic. Among dialysis patients, sleep disturbance is associated with depression and poorer HRQOL. The study was designed to depict the prevalence of sleep disturbance, and to explore the association among sleep, depression, and HRQOL in patients with non-dialysis chronic kidney disease (CKD) during the COVID-19 pandemic. A total of 172 non-dialysis CKD patients enrolled in this cross-sectional study, with sociodemographic and clinical data recorded. Sleep, HRQOL, and depression were evaluated via the Pittsburgh Sleep Quality Index (PSQI), the Kidney Disease Quality of Life 36-Item Short-Form Survey (KDQOL-36), and the 9-item Patient Health Questionnaire (PHQ-9), respectively. A total of 100 (58%) met the criteria for poor sleep. Good sleepers had strikingly disparate HRQOL and depression scores compared to poor sleepers. Sleep disorders were significantly associated with decreased HRQOL and increased depression in regression models adjusted or unadjusted for sociodemographic and clinical characteristics. Mediation analysis indicated depression was a significant mediator explaining 51% of the relationship between sleep status with physical component summary (PCS) and played a fully mediating role in the association between sleep and mental component summary (MCS). Our study suggested the high incidence of sleep disorders in patients with non-dialysis CKD during the COVID-19 pandemic, as well as the tight associations among sleep, depression, and HRQOL. Considering the negative influences of sleep and depression on HRQOL, appropriate screening and treatment for these treatable health-related domains are necessary for patients with non-dialysis CKD.


Breakthrough candidemia in patients with cancer differs from de novo candidemia in host factors and Candida species but not intensity.
To evaluate the risk factors associated with breakthrough candidemia in patients with cancer and to compare them with those of de novo candidemia in this patient population. Retrospective case series of 120 episodes of candidemia, 90 de novo and 30 breakthrough candidemias. University-affiliated, tertiary-care cancer center in Houston, Texas. All patients with cancer who acquired candidemia between January 1993 and December 1998 were included if they had non-catheter-related candidemia and information about quantitative blood cultures. Although less frequent, breakthrough candidemia was seen more often in neutropenic patients with leukemia. The intensity of breakthrough candidemia was comparable to that of de novo candidemia. Most (70%) of the breakthrough candidemias were due to Candida glabrata or C. krusei. In breakthrough candidemia, the same risk factors seen in de novo candidemia were encountered, although more frequently. C. glabrata and C. krusei are the leading causes of breakthrough candidemia in patients with cancer.


Autologous cell therapy in diabetes‑associated critical limb ischemia: From basic studies to clinical outcomes (Review).
Cell therapy is becoming an attractive alternative for the treatment of patients with no‑option critical limb ischemia (CLI). The main benefits of cell therapy are the induction of therapeutic angiogenesis and neovascularization that lead to an increase in blood flow in the ischemic limb and tissue regeneration in non‑healing cutaneous trophic lesions. In the present review, the current state of the art of strategies in the cell therapy field are summarized, focusing on intra‑operative autologous cell concentrates in diabetic patients with CLI, examining different sources of cell concentrates and their mechanisms of action. The present study underlined the detrimental effects of the diabetic condition on different sources of autologous cells used in cell therapy, and also in delaying wound healing capacity. Moreover, relevant clinical trials and critical issues arising from cell therapy trials are discussed. Finally, the new concept of cell therapy as an adjuvant therapy to increase wound healing in revascularized diabetic patients is introduced.


Digital opportunities to connect and complain - the use of Facebook in small animal practice.
Social media is increasingly used in small animal practice, enabling veterinarians to connect with clients and promote their business online. It can also be used by clients to quickly distribute complaints via online communities. Using a questionnaire study we investigated Austrian, Danish and UK veterinarians' attitudes towards Facebook, the contents of clients' online complaints and how they were handled by veterinarians (N = 648). In Denmark and the UK, around 90% of practices had a Facebook page, in contrast to 40% of Austrian practices. Most Danish and UK veterinarians agreed that the use of Facebook was relevant and expected by clients. Agreement was lower among Austrian veterinarians, probably reflecting the lower uptake of social media there. In particular, younger veterinarians and those who actively used Facebook for the practice, could see benefits. In all three countries, we found that clients most frequently complained about treatment costs. Most veterinarians preferred to actively deal with clients' complaints, either replying online or discussing them directly. We recommend future research focusing on veterinarians' personal use of social media and on clients' use of and attitudes towards social media in the veterinary context.


[Risk factors for atopic dermatitis and familial prevalence in Spain (ELIHO study)].
Atopic dermatitis (AD) is a cutaneous disease of unknown etiology. It shows a clear genetic predisposition with probable environmental modulation. This study evaluated risk factors associated with diagnosis and flares of AD in Spanish children. We performed an observational, multicenter, retrospective case-control study that included 4243 children aged less than 14 years old with AD and 978 controls matched for age and sex. Family history of disease and environmental variables were collected in both groups and clinical history of AD was recorded in the case group. Significant risk factors for AD were: a family history of the disease and concomitant cutaneous infections. The prevalence of AD in first degree relatives was 39 % and that in second degree relatives was 19 % (higher in maternal than paternal lines). The mean age of children with AD was 4.2 (SD 3.4) years and the mean age at diagnosis was 1.5 (SD 2.2) years, with a mean of 2.9 (SD 2.6) flares during the previous year. Cold weather (Cantabrian and Continental Iberian Peninsula areas) was related to a greater number of flares. Children with AD had a greater number of concomitant cutaneous diseases and infections than children in the control group. AD is mainly a genetic disease, with climatic factors involved in severity modulation, and with important immunological alterations. In contrast, this study found no domestic environmental factors that were associated with disease onset.


Mental alertness in response to hypoglycaemia in normal man: the effect of 12 hours and 72 hours of fasting.
To study the influence of hypoglycaemia and starvation on mental functions eight healthy male students age 25-34 years with an ideal body mass of 99.9% +/- 2.5% (mean +/- SEM) were recruited. Hypoglycaemia was induced in random order by an insulin-glucose clamp technique (insulin: 2.4 mU/kg/min + glucose at variable rate) keeping the venous blood glucose at 2.2 mmol/l both after an overnight fast and after 72 h fasting. Mental alertness was assessed by measuring the recognition time, moving time and total reaction time to a visual signal and by a verbal mental clearness test and a synonym learning test during normo- as well as hypoglycaemia. Hypoglycaemia prolonged the total reaction time (p less than 0.05) and the time required for the mental clearness test (p less than 0.05). Compared with a control study performed at normoglycaemia the learning effect of the synonym test was reduced by hypoglycaemia. Fasting, which resulted in a body weight reduction of 2.6 +/- 0.3 kg and ketonuria prolonged the total reaction time (p less than 0.005) by increasing the moving time but did not affect the mental clearness test. When hypoglycaemia was preceded by 72 h fasting it did not increase the total reaction time, nor did it modify the mental clearness test. Moreover, the learning effect of the synonym test was less impaired. In conclusion, mental alertness was reduced by moderate hypoglycaemia after an overnight fast while similar hypoglycaemia did not reduce mental alertness after prolonged fasting. This may illustrate a decrease of the glucose dependency of the central nervous system during prolonged fasting.


Ophthalmic Insert versus Eye Drops for Mydriasis in Neonates: A Randomized Clinical Trial.
Eye drop treatment routinely used to obtain mydriasis prior to fundoscopy in neonates requires repeated instillations of mydriatic agents that can lead to systemic side effects. The aim of this study was to compare the mydriatic efficacy and tolerance of administration of phenylephrine and tropicamide via the ophthalmic insert Mydriasert® versus standard eye drop treatment in neonates. In this prospective, single-blinded, noninferiority study, 80 hospitalized neonates (age < 18 months) requiring bilateral fundus examination were randomized to receive eye drops (repeated instillations of 2.5% phenylephrine and 0.5% tropicamide) or the insert. The primary outcome was mydriasis suitable for fundoscopy 75 min after mydriatic agent introduction (T75). Mydriasis was successfully achieved in both eyes at T75 in 97.5% (n = 39/40) of the insert group patients versus 90% (n = 36/40) receiving eye drops (between-group difference 7.5%, demonstrating noninferiority). Mydriasis remained stable in 60.0% of patients (n = 24/40) in the insert group versus 15% (n = 6/40) in the eye drop group (p < 0.0001). The insert group required fewer nursing interventions than the eye drop group (p = 0.0001). Mean blood pressure were significantly higher in the insert versus the eye drop group (p < 0.0001 and p = 0.0003, respectively); mean heart rate was not significantly different between the groups (p = 0.37). In the insert group, 2 patients reported an adverse event (bradycardia, n = 1, and gastroesophageal reflux, n = 1; both appeared to be related to neonate pathology). The degree of mydriasis achieved with Mydriasert® was noninferior to that obtained with eye drops. The insert appears to be safe to use in neonates without a history of increased vagal tone or gastrointestinal reflux.


b-Type Cytochromes in Higher Plant Plasma Membranes.
The composition and characteristics of b-type cytochromes from higher plant plasma membranes, purified using aqueous two-phase partitioning, were investigated. At least three different cytochromes were identified by their wavelength maxima and redox midpoint potentials (E(0)'). Cytochrome b-560.7 (E(0)' from + 110 to + 160 millivolts) was present in zucchini (Cucurbita pepo) hypocotyls and bean (Phaseolus vulgaris L.) hooks, although in different concentrations. The main component in cauliflower (Brassica oleracea L.) inflorescences (cytochrome b-558.8) is probably functionally similar to this cytochrome. The plasma membrane generally contains two to three cytochrome species. However, the occurrence and concentrations were species dependent. The high potential cytochrome can be reduced by ascorbate but not NADH, and may be involved in blue light perception.


Xanthones from roots of Calophyllum thwaitesii and their bioactivity.
Extracts from three Calophyllum species endemic to Sri Lanka were tested for antifungal and antioxidant activities. Of them, only the root methanol extract of Calophyllum thwaitesii showed activity, and the active extract on activity guided fractionation yielded four antifungal active and three inactive xanthones. Antifungal active xanthones were identified as 1,6-dihydroxy-5-methoxyxanthone, 1-hydroxy-5,6-dimethoxyxanthone, 1-hydroxy-5-methoxyxanthone and 1-methoxy-5-hydroxyxanthone, using spectroscopic methods and comparison with literature data. Inactive compounds were identified as 1-hydroxy-7-methoxyxanthone, 1,5-dihydroxy-6-methoxyxanthone and 1,7-dihydroxy xanthone. This is the first report of above xanthones except the latter from C. thwaitesii. Further, five of the above xanthones along with thwaitesixanthone and calothwaitesixanthone, which have been previously reported from the root bark of the same species, showed free radical scavenging properties when tested with DPPH. Further, this is the first report of methylated xanthones from C. thwaitesii. Previous work on stem bark, root bark and the stem of the same species yielded only nonmethylated xanthones, indicating the absence of methylating enzymes in the plant. However, this new finding suggests the presence of methylating enzymes in the root stem of C. thwaitesii.


Rational Design and Synthesis of HSF1-PROTACs for Anticancer Drug Development.
PROTACs employ the proteosome-mediated proteolysis via E3 ligase and recruit the natural protein degradation machinery to selectively degrade the cancerous proteins. Herein, we have designed and synthesized heterobifunctional small molecules that consist of different linkers tethering KRIBB11, a HSF1 inhibitor, with pomalidomide, a commonly used E3 ligase ligand for anticancer drug development.


The evolution of high summit metabolism and cold tolerance in birds and its impact on present-day distributions.
Summit metabolic rate (M(sum), maximum cold-induced metabolic rate) is positively correlated with cold tolerance in birds, suggesting that high M(sum) is important for residency in cold climates. However, the phylogenetic distribution of high M(sum) among birds and the impact of its evolution on current distributions are not well understood. Two potential adaptive hypotheses might explain the phylogenetic distribution of high M(sum) among birds. The cold adaptation hypothesis contends that species wintering in cold climates should have higher M(sum) than species wintering in warmer climates. The flight adaptation hypothesis suggests that volant birds might be capable of generating high M(sum) as a byproduct of their muscular capacity for flight; thus, variation in M(sum) should be associated with capacity for sustained flight, one indicator of which is migration. We collected M(sum) data from the literature for 44 bird species and conducted both conventional and phylogenetically informed statistical analyses to examine the predictors of M(sum) variation. Significant phylogenetic signal was present for log body mass, log mass-adjusted M(sum), and average temperature in the winter range. In multiple regression models, log body mass, winter temperature, and clade were significant predictors of log M(sum). These results are consistent with a role for climate in determining M(sum) in birds, but also indicate that phylogenetic signal remains even after accounting for associations indicative of adaptation to winter temperature. Migratory strategy was never a significant predictor of log M(sum) in multiple regressions, a result that is not consistent with the flight adaptation hypothesis.


The adipose tissue of origin influences the biological potential of human adipose stromal cells isolated from mediastinal and subcutaneous fat depots.
Indirect evidence suggests that adipose tissue-derived stromal cells (ASCs) possess different physiological and biological variations related to the anatomical localization of the adipose depots. Accordingly, to investigate the influence of the tissue origin on the intrinsic properties of ASCs and to assess their response to specific stimuli, we compared the biological, functional and ultrastructural properties of two ASC pools derived from mediastinal and subcutaneous depots (thoracic compartment) by means of supplements such as platelet lysate (PL) and FBS. Subcutaneous ASCs exhibited higher proliferative and clonogenic abilities than mediastinal counterpart, as well as increased secreted levels of IL-6 combined with lower amount of VEGF-C. In contrast, mediastinal ASCs displayed enhanced pro-angiogenic and adipogenic differentiation properties, increased cell diameter and early autophagic processes, highlighted by electron microscopy. Our results further support the hypothesis that the origin of adipose tissue significantly defines the biological properties of ASCs, and that a homogeneric function for all ASCs cannot be assumed.


Metal displacement and stoichiometry of protein-metal complexes under native conditions using capillary electrophoresis/mass spectrometry.
Increases in the study of protein-metal complexes, as well as in metal displacement in protein-metal complexes under native conditions for optimum catalytic properties in drug research and catalyst design, demands a separation/detection technology that can accurately measure metal displacement and stoichiometry in protein-metal complexes. Both nuclear magnetic resonance (NMR) and X-ray diffraction techniques have been used for this purpose; however, these techniques lack sensitivity. Electrospray ionization mass spectrometry (ESI-MS) using direct infusion offers higher sensitivity than the former techniques and provides molecular distribution of various protein-metal complexes. However, since protein-metal complexes under native conditions usually are dissolved in salt solutions, their direct ESI-MS analysis requires off-line sample clean-up prior to MS analysis to avoid sample suppression during ESI. Moreover, direct infusion of the salty solution promotes non-specific salt adduct formation by the protein-metal complexes under ESI-MS, which complicates the identification and stoichiometry measurements of the protein-metal complexes. Because of the high mass of protein-metal complexes and lack of sufficient resolution by most mass spectrometers to separate non-specific from specific metal-protein complexes, accurate protein-metal stoichiometry measurements require some form of sample clean up prior to ESI-MS analysis. In this study, we demonstrate that capillary electrophoresis/electrospray ionization in conjunction with a medium-resolution (approximately 10,000) mass spectrometer is an efficient and fast method for the measurement of the stoichiometry of the protein-metal complexes under physiological conditions (pH approximately 7). The metal displacement of Co(2+) to Cd(2+), two metal ions necessary for activation in the monomeric AHL lactonase produced by B. thuringiensis, has been used as a proof of concept.


[Survey of newly diagnosed leprosy patients in Japan (1993-2000)].
We analyzed the medical and social problems of newly registered leprosy patients in the past 8 years from 1993 to 2000 in a low endemic country, Japan. There were 56 registered Japanese patients (males, 32; females, 24), and 76 registered foreign patients (males, 56; females, 20). The number of Japanese patients in each year was between 5 and 9, and 2/3 of them were from Okinawa Prefecture, located in subtropical zone. But the number of foreign patients in each year was between 5 and 18, and 2/5 of them were from Brazil. The number of foreign patients was greater than that of Japanese patients. Male/female ratio has decreased among the Japanese.


Clostridium difficile toxin B disrupts the barrier function of T84 monolayers.
The contribution of toxin B to Clostridium difficile-associated infection is undefined. Toxin B induces dramatic phenotypic alterations (cytotoxic effects) in cultured mesenchymal and nonintestinal epithelial cells, yet its effects on intestinal epithelial cells are not clearly understood. The alterations induced by toxin B in nonintestinal cells appear to be secondary to toxin-induced redistribution of filamentous actin. It has not been determined whether toxin B exerts similar effects on cultured intestinal epithelial cells or whether such phenotypic alterations are of any physiological consequence. To address these questions, we examined the effect of C. difficile toxin B on the phenotype and barrier function of T84 cell monolayers. Our studies show that the cytotoxic effects of toxin B, i.e., cell rounding, do extend to cultured intestinal epithelial cells (T84). In addition, toxin B dramatically reduces the barrier function of T84 monolayers grown on collagen-coated filters. Toxin B-induced redistribution of filamentous actin appears to be responsible for the alterations in both intestinal epithelial cell phenotype and barrier function. Specifically, filamentous actin comprising the perijunctional actomyosin ring, known to be important in regulating tight junction permeability, is condensed into discrete plaques. Flux studies confirm that the permeability defect is at the level of the tight junction. We conclude that toxin-induced changes in actin distribution perturb intercellular junctional contacts and thereby ablate epithelial barrier function. There was no evidence of cell death as determined by lactate dehydrogenase release assays.


Efficacy of non-opioid analgesics to control postoperative pain: a network meta-analysis.
The aim of this network meta-analysis (NMA) was to evaluate the safety and efficacy of intravenous (IV) Meloxicam 30 mg (MIV), an investigational non-steroidal anti-inflammatory drug (NSAID), and certain other IV non-opioid analgesics for moderate-severe acute postoperative pain. We searched PubMed and CENTRAL for Randomized Controlled Trials (RCT) (years 2000-2019, adult human subjects) of IV non-opioid analgesics (IV NSAIDs or IV Acetaminophen) used to treat acute pain after abdominal, hysterectomy, bunionectomy or orthopedic procedures. A Bayesian NMA was conducted in R to rank treatments based on the standardized mean differences in sum of pain intensity difference from baseline up to 24 h postoperatively (sum of pain intensity difference: SPID 24). The probability and the cumulative probability of rank for each treatment were calculated, and the surface under the cumulative ranking curve (SUCRA) was applied to distinguish treatments on the basis of their outcomes such that higher SUCRA values indicate better outcomes. The study protocol was prospectively registered with by PROSPERO (CRD42019117360). Out of 2313 screened studies, 27 studies with 36 comparative observations were included, producing a treatment network that included the four non-opioid IV pain medications of interest (MIV, ketorolac, acetaminophen, and ibuprofen). MIV was associated with the largest SPID 24 for all procedure categories and comparators. The SUCRA ranking table indicated that MIV had the highest probability for the most effective treatment for abdominal (89.5%), bunionectomy (100%), and hysterectomy (99.8%). MIV was associated with significantly less MME utilization versus all comparators for abdominal procedures, hysterectomy, and versus acetaminophen in orthopedic procedures. Elsewhere MME utilization outcomes for MIV were largely equivalent or nominally better than other comparators. Odds of ORADEs were significantly higher for all comparators vs MIV for orthopedic (gastrointestinal) and hysterectomy (respiratory). MIV 30 mg may provide better pain reduction with similar or better safety compared to other approved IV non-opioid analgesics. Caution is warranted in interpreting these results as all comparisons involving MIV were indirect.


Orientin mitigates 1, 2-dimethylhydrazine induced lipid peroxidation, antioxidant and biotransforming bacterial enzyme alterations in experimental rats.
Colorectal cancer (CRC) is the second most diagnosed cancer often identified during the later stages of carcinogenesis. Orientin, a C-glycoside of luteolin, is well known for its versatile therapeutic action toward oxidative stress-induced cellular response may exert chemoprevention against CRC. In our study, we investigated the modulatory effect of orientin on lipid peroxidation, antioxidant defense, and biotransforming bacterial enzymes in 1, 2-dimethylhydrazine (DMH)-induced male albino Wistar rats in a dose-dependent manner. Animals were induced with DMH (20 mg/kg b.wt) for 15 weeks and administered with orientin in three different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg b. wt) daily under distinct phases (initiation, postinitiation, and the entire) for a total treatment period of 30 weeks. Orientin reinstates the alterations induced by DMH on lipid peroxidation and enzymatic antioxidants through its rich-free radical scavenging properties. In addition, orientin curtails the DMH-induced augmentation of biotransforming bacterial enzymes to inhibit the colon cancer progression. Overall, experimental findings suggest that orientin significantly inhibits the DMH induced colon cancer in all the three different doses, however, maximum inhibition was observed on supplementation of 10 mg/kg b.wt for the entire period of the study. Hence, the intraperitoneal administration of 10 mg/kg b.wt orientin for the entire period is recommended for further molecular investigation to elucidate the precise mechanism of inhibition and so orientin can be used as a novel chemotherapeutic agent for CRC.


Factors affecting the dose of methadone among patients receiving methadone maintenance therapy in Taiwan.
Methadone maintenance treatment (MMT) has been shown to be an effective therapeutic strategy for opioid users. This study aimed to investigate the predictive effect of clinically predominant sleep disturbance (CPSD) on the dose of methadone among opiate users receiving MMT during a follow-up period of 6 years in Taiwan. This retrospective study included 1,290 individuals with opioid dependence who visited our MMT clinic for the first time. Generalized estimating equations were used to analyze the effect of CPSD on the daily dose of methadone by controlling for the effects of demographic and MMT characteristics. A total of 469 (36.4%) participants were comorbid with CPSD. After controlling for the effects of demographic and MMT characteristics, the participants comorbid with CPSD had a higher dose of daily methadone than those without CPSD (estimate: 7.03, p < .001). Furthermore, younger age (estimate: -1.22, p < .001), older age at initial MMT (estimate: .44, p < .001), lower educational level (estimate: -.90, p = .003) and lower attendance rates (estimate: -.14, p = .033) are significantly related to higher doses of daily methadone. Our study provided a naturalistic observation of the cohort for long period, along with a large sample size which could reflect clinical practice in the real world. We reported that a higher daily dose of methadone was significantly associated with CPSD after controlling for the effects of other factors. CPSD should be routinely surveyed among heroin users receiving MMT. (Am J Addict 2018;27:225-230).


Structure of the adipate complex [Na2(C6H9O4)2(C6H10O4)].2H2O from neutron diffraction at 220 and 295 K.
The crystal structure of sodium hydrogen adipate-adipic acid (2/1) dihydrate, [Na2(C6H9O4)2(C6H10O4)].2H2O, Mr = 518.4, has been determined from neutron diffraction data collected at 220 and 295 K. Crystals are monoclinic, space group C2/m, with Z = 2. At 295 K, a = 9.378 (2), b = 13.379 (5), c = 10.247 (3) A, beta = 95.93 (3) degrees, V = 1278.8 (7) A3, Dn = 1.346, Dm = 1.348 (1) g cm-3 (in dibromomethane/bromobutane), lambda = 1.1588 (2) A, mu = 2.186 cm-1, F(000) = 176.4 fm, R(F2) = 0.108 for all 1995 nonequivalent reflections with sin theta/lambda less than 0.71 A-1. The crystal structure is similar at 220 K except for reduced nuclear mean-square displacements. Hydrogen adipate subunits (called A) are linked end-to-end in infinite chains by very short O...O (2.44 A) hydrogen bonds where the H nuclei are on centers of symmetry within the experimental error. The Na cation is octahedrally coordinated by O atoms from molecules A and also by non-ionized adipic acid molecules (called B). The B molecules have large mean-square nuclear displacements which are described in terms of anharmonicity and disorder.


The effect of magnetization of natural rubber latex-coated magnetite nanoparticles on shear wave dispersion magneto-motive ultrasound.
The shear wave dispersion magneto-motive ultrasound (SDMMUS) method was recently developed to analyze the mechanical properties of a viscoelastic medium. This technique is based on the interaction of magnetic nanoparticles (MNPs) with an external magnetic field to generate a shear wave within the medium labeled with MNPs. The propagation of this wave provides information about the viscoelastic properties of the medium. In a previous work by Arsalani et al (2018), magnetite NPs were synthesized by a co-precipitation method and coated with natural rubber latex (NRL). In order to investigate the effect of NRL on the size and magnetization of MNPs, varying amounts of NRL (zero, 100 µl, and 800 µl of a stock solution of NRL) were used during the synthesis process. The results showed that MNPs prepared with 800 µl of NRL, named as MNPs-800NRL, had the smallest size and highest magnetization. In the present paper, the main objective is to investigate whether MNPs-800NRL, having the highest magnetization, is also the best option for SDMMUS experiments among others. All experiments were performed using gelatin tissue-mimicking phantoms labeled with the aforementioned MNPs. The two factors of core size and magnetization were considered, and based on the observed results, the effect of magnetization was more prominent than that of the core size on the induced displacements. MNPs coated with a thicker NRL shell, having the highest magnetization value, enhanced the sensitivity and the signal to noise ratio in SDMMUS. Various concentrations of these optimized MNPs were also examined, to investigate the lowest possible concentration for observing shear waves in the SDMMUS technique.


Meta-analysis of studies in China about changes in P300 latency and amplitude that occur in patients with schizophrenia during treatment with antipsychotic medication.
Studies using event-related potential (ERP) methods have reported a relationship between the cognitive dysfunction of patients with schizophrenia and P300 latency and amplitude, but it remains uncertain whether or not these indices change as cognitive functioning improves with pharmacological treatment. Pool the results from follow-up studies conducted in China to determine the relationship of treatment with antipsychotic medication to changes in P300 indices. Studies conducted in China and published in English or Chinese from January 1982 to December 2011 that reported P300 latency and amplitude in patients with schizophrenia before and after treatment with antipsychotic medications were identified by electronic and hand searches, and the 12 studies that met inclusion criteria for the meta-analysis were independently reviewed by two evaluators. The peak P300 amplitude results for the 17 samples reported in the 12 studies were homogenous so a fixed-effects model was used to assess pooled standardized effect size (PSES); but the results for P300 latency were heterogeneous so a random-effects model was used to compute PSES. Publication bias was assessed using Egger's test, Begg's test and funnel plots. Of the pooled sample of 611 participants, the 502 participants (82.2%) who completed P300 latency and amplitude measures both before and after treatment were included in the meta-analysis. We found that antipsychotic treatment is associated with a small but significant increase in the amplitude of P300 (PSES=0.39, 95% CI [0.26, 0.51], z=6.14, p<0.001) and a small but significant decrease in the latency of P300 (PSES= -0.29, 95% CI [-0.51, -0.07]; z=2.58; p=0.010). There was no significant publication bias in either of the results. In contrast to meta-analysis from western countries - that are primarily based on cross-sectional studies - the current meta-analysis of follow-up treatment studies of schizophrenia in China found that P300 amplitude and latency both change with pharmacological treatment. These findings suggest that P300 indices, particularly P300 amplitude, could be valuable biomarkers to monitor changes in cognitive functioning during treatment of patients with schizophrenia.


Effects of hand massage on anxiety in cataract surgery using local anesthesia.
To evaluate the effects of hand massage on patient anxiety during cataract surgery. Kangnam St. Mary's Hospital, Seoul, Korea. This study comprised 59 patients having cataract surgery from December 11, 1996, to February 12, 1997. The patients were divided into those having a hand massage 5 minutes before surgery (experimental group, n = 29) and those not receiving a hand massage (control group, n = 30). Patients' anxiety levels were measured using the Visual Analog Scale and by assessing the systolic blood pressure, diastolic blood pressure, and pulse rate before and after the hand massage and 5 minutes before the end of surgery. Epinephrine, norepinephrine, cortisol, blood sugar levels, neutrophil, and lymphocyte percentages in white blood cells were also measured. After the hand massage, the psychological anxiety levels, systolic and diastolic blood pressures, and pulse rate were significantly lower than before the massage. The hand massage significantly decreased epinephrine and norepinephrine levels in the experimental group. Epinephrine, norepinephrine, and cortisol levels increased in the control group. The differences between groups were significant. There were no significant between-group differences in blood sugar levels or neutrophil and lymphocyte percentages in white blood cells. The findings indicate that hand massage decreases the psychological and physiological anxiety levels in patients having cataract surgery under local anesthesia.


Bioenvironmental control of industrial malaria at Bharat Heavy Electricals Ltd., Hardwar, India--results of a nine-year study (1987-95).
A bioenvironmental model to control malaria at Bharat Heavy Electricals Ltd. in Hardwar was developed by using existing resources to reduce mosquito breeding. The civil maintenance department carried out major source reduction work by filling pits, low lying areas, ditches, etc., with fly ash from a coal-fired power station, construction of stand posts and proper drainage, mosquito proofing of overhead tanks, and preventive maintenance of the water supply and the sewage system. The project staff has applied 1) expanded polystyrene beads to underground tanks, leaking sluice valve chambers, and blocked sewage manholes; 2) biolarvicides to water accumulated in factory scraps, blocked drains, and riverbed pools, and 3) larvivorous fish to storm water drains, effluent ponds, and drains for the effective control of mosquito breeding. Improved surveillance and treatment coupled with comprehensive developmental schemes were additional tools to gain community support. As a result of intervention measures, the vector density in the township was significantly lowered compared to that of a control area, and there was a drastic reduction in malaria incidence compared to that of the preintervention year: only 190 cases were recorded in 1995, compared to 3,049 cases in 1985. The study has shown that malaria control in an industrial township through an integrated control approach is practical, sustainable, and economically feasible and reduces insecticide pollution in the environment.


Spectral broadening of mid-infrared femtosecond pulses in GaAs.
We achieved efficient spectral broadening for mid-IR pulses of few-microjoule energy. The spectral bandwidth of the femtosecond pulses at the center wavelength of 5000 nm increased from 540 nm to 2060 nm (from 220 to 910 cm(-1) in frequency) by nonlinear propagation in a gallium arsenide single crystal. The spectral broadening was accompanied by nonlinear absorption loss of 25%. The demonstrated scheme should be available at any operation wavelength within the material transparency range and provides a useful tool in nonlinear vibrational spectroscopy.


Direct chloroplast sequencing: comparison of sequencing platforms and analysis tools for whole chloroplast barcoding.
Direct sequencing of total plant DNA using next generation sequencing technologies generates a whole chloroplast genome sequence that has the potential to provide a barcode for use in plant and food identification. Advances in DNA sequencing platforms may make this an attractive approach for routine plant identification. The HiSeq (Illumina) and Ion Torrent (Life Technology) sequencing platforms were used to sequence total DNA from rice to identify polymorphisms in the whole chloroplast genome sequence of a wild rice plant relative to cultivated rice (cv. Nipponbare). Consensus chloroplast sequences were produced by mapping sequence reads to the reference rice chloroplast genome or by de novo assembly and mapping of the resulting contigs to the reference sequence. A total of 122 polymorphisms (SNPs and indels) between the wild and cultivated rice chloroplasts were predicted by these different sequencing and analysis methods. Of these, a total of 102 polymorphisms including 90 SNPs were predicted by both platforms. Indels were more variable with different sequencing methods, with almost all discrepancies found in homopolymers. The Ion Torrent platform gave no apparent false SNP but was less reliable for indels. The methods should be suitable for routine barcoding using appropriate combinations of sequencing platform and data analysis.


Pbx1 is required for Hox D3-mediated angiogenesis.
Our previous studies showed that the homeobox (Hox) D3 transcription factor induces expression of alphavbeta3 integrin and promotes endothelial cell (EC) migration and angiogenesis. Since binding of Hox 3 factors to target DNA is enhanced by the co-factor Pbx, we investigated whether Pbx1 is also required for angiogenesis. We observed that EC predominantly express the Pbx1b isoform. Nuclear extracts from angiogenic EC express higher levels of active Pbx1 and more effectively form complexes on Pbx1/Hox consensus DNA oligonucleotides as compared to nuclear extracts from quiescent EC. Introduction of anti-sense against Pbx1 impaired the formation of Pbx1/Hox complexes on target DNA consensus in nuclear extracts from angiogenic EC. Anti-sense against Pbx1 also impaired EC migration and blocked angiogenesis induced by bFGF in vivo. Furthermore, although the levels of Hox D3 were unchanged, expression of its target gene, beta3 integrin was reduced, consistent with impaired transcriptional activation by Hox D3. Together, these studies suggest that Pbx1 is required for pro-angiogenic Hox DNA binding and transcriptional activity in endothelial cells.


Alcoholic parents and their children.
Some 211 male alcoholic in-patients were compared with a simple random sample of 200 men from Greater Stockholm. The group of male alcoholic in-patients and the random sample were subdivided with respect to alcohol consumption and use of hepatotoxic drugs: (IA) men from the random sample with low or moderate alcohol consumption and no use of drugs (n = 169); (IB) men from the random sample with low or moderate alcohol consumption with use of drugs (n = 31); (IIA) alcoholic in-patients with use of alcohol but no drugs (n = 171); (IIB) alcoholic in-patients with use of alcohol and drugs (n = 40). Earlier and more severe alcohol-related and anti-social problems were found among subjects with an alcoholic parent than among subjects without an alcoholic parent. The highest level of problems was noted for subjects with alcoholism in both parents and among the alcoholic in-patients. Groups which resembled each other were the drug users in the alcoholic group and in the general sample. Both inherited and environmental factors are important determinants and many of these individuals have psycho-social problems as children and adults. The children of those adults who used alcohol in combination with drugs (IIB) had most problems and the most severe problems. In the general population sample, those who used alcohol in combination with drugs (IB) had so many problems in the family and psycho-social problems themselves that they resembled the alcoholic in-patients and especially the group with high alcohol consumption in combination with drugs (IIB). A new finding is that the high-risk groups IB and IIB, who used both alcohol and drugs, had experienced a more disturbed school career and were more aggressive, had more nervous problems, and were more emotionally disturbed than the other groups. It is concluded that alcohol and drug use by parents may be predictive of future alcoholism in their children.


Pulmonary nodules in osteosarcoma patients: differential diagnosis of central venous catheter-related infections in the lungs.
The purpose of this study was to evaluate the differential diagnosis of pulmonary nodules by conventional radiography and computed tomography (CT) in osteosarcoma patients with central venous catheter. Between March 1997 and December 2001 at our Department of Musculoskeletal Oncology, 231 patients with peripheral osteosarcoma received a central venous catheter to allow infusion therapy and blood sampling. The mean age of these patients was 16 years (range 4-63), and 90 were aged 15 years or younger. All patients underwent radiological investigation for tumour staging and comparison with the following study in accordance with the protocol in place at our Department of Oncology and Division of Diagnostic Imaging. Of a total of 231 patients, 13 (5.6%) developed an infection of the central venous line, with fever that was very high in some cases. In ten cases (4.3%), radiology showed damage to the alveolar interstitium typical of inflammatory forms, whereas in the remaining three (1.3%) it depicted nodular opacities, which required differentiation between lung metastases and septic emboli. After appropriate antibiotic and replacement of the central venous line, CT demonstrated disappearance of the lung nodules in all three patients, enabling a diagnosis of nodular septic embolism. Placement of a central venous catheter for infusion therapy, chemotherapy and blood sampling has improved the quality of life of cancer patients. The most common complications of the use of central venous catheters include infection and venous thrombosis whereas pulmonary septic emboli are rare.


Budget Impact Analysis of Metformin Sustained Release for the Treatment of Type 2 Diabetes in The Netherlands.
Adverse drug reactions and medication nonadherence are well-known causes of sub-optimal disease control and worsened disease outcomes in patients who are treated for type 2 diabetes. Metformin sustained release (SR) might reduce these adverse events and improve medication adherence via a simplified treatment regimen for metformin immediate release (IR)-intolerant patients. The aim of this study is to estimate the budget impact of metformin SR for the treatment of type 2 diabetes in the Netherlands, compared to the current standard of care (SoC) with metformin IR. A budget impact model was built to represent the course of the disease and treatment pathway of type 2 diabetes patients eligible for metformin SR from a healthcare payer's perspective. Patients were considered eligible if they used less than 2000 mg metformin IR per day, but suffered from adverse events that might lead to therapy discontinuation, and if they were newly diagnosed with type 2 diabetes. The costs of type 2 diabetes treatment and related complications over a time horizon of 3 years were calculated. Univariate sensitivity analyses were conducted to show which parameters have the biggest influence on the budget impact. The budget impact analysis showed cost-savings of - €1,962,335 over a period of 3 years through implementation of metformin SR as an alternative to SoC with metformin IR. Savings were mostly driven by the delay of other, more expensive type 2 diabetes treatments, such as insulin. In sensitivity analyses, medication adherence and persistence appeared to have the biggest influence on the budget impact. Metformin SR could potentially be a cost-saving alternative to metformin IR for the treatment of type 2 diabetes in the Netherlands, especially in patients experiencing adverse events with metformin IR. However, more research is needed to better predict the effect of using once-daily metformin, compared to multiple dosages, on medication adherence and persistence and to evaluate whether metformin SR really decreases the amount of adverse events.


Development of Indirect Competitive ELISA and Visualized Multicolor ELISA Based on Gold Nanorods Growth for the Determination of Zearalenone.
In this study, a zearalenone (ZEN) hapten was designed and prepared against the mycotoxin ZEN, and the original coating ZEN-ovalbumin (ZEN-OVA) was prepared by conjugation with OVA. Based on the gold nanorods (AuNRs) of uniform size and stable properties synthesized by the seed-mediated method, the indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and the AuNRs growth-based multicolor ELISA for detecting ZEN toxin were further established. Under the optimal experimental conditions, the coating amount of ZEN-OVA: 0.025 μg/well, antibody (Ab) dilution factor: 32,000 times, blocking solution: 0.5% skimmed milk powder, enzyme-labeled secondary Ab diluted 10,000 times, and a pH of the PBS buffer at 7.4, the sensitivity (IC50) of the established ic-ELISA for ZEN detection reached 0.85 ± 0.04 μg/L, and the limit of detection (IC15) reached 0.22 ± 0.08 μg/L. In the multicolor ELISA based on the growth of AuNRs, as the content of ZEN increased, the mixed solution exhibited a significant color change from brownish red to colorless. ZEN concentration as low as 0.1 μg/L can be detected by the naked eye (brown red to dark gray). This study provided an effective analysis strategy for the rapid screening and accurate monitoring of the ZEN contaminant in foods.


A continuous assay of hepatitis C virus protease based on resonance energy transfer depsipeptide substrates.
Hepatitis C virus (HCV) is the major causative agent of non-A non-B hepatitis, an important health problem with an estimated 50 million people infected worldwide. Among the possible targets for therapeutic intervention, the serine protease contained within the N-terminal region of nonstructural protein 3 (NS3 protease) is so far the best characterized. In vitro characterization of synthetic substrates based on all the natural cleavage sites (as well as a series of analogs) has consistently revealed poor kinetic parameters, making them unsuitable for sensitive high-throughput screening. To overcome these difficulties, we have recently developed depsipeptide substrates incorporating an ester bond between residues P1 and P&prime1. Due to ready transesterification of the scissile bond to the acyl-enzyme intermediate, these substrates showed very high kcat/Km values, enabling detection of activity with subnanomolar NS3 concentrations. We have used the same principle to synthesize internally quenched depsipeptide fluorogenic substrates based on resonance energy transfer between the donor/acceptor couple 5-[(2'-aminoethyl)amino]naphthalene sulfonic acid/4-[[4'-(dimethylamino)phenyl]azo]benzoic acid, and developed a continuous assay for NS3 activity. Substrate cleavage is linear with enzyme concentration: depending on the conditions chosen, we estimated a detection limit for NS3 between 1 nM and 250 pM. The suitability of the assay for evaluation of inhibitors was established using as competitor a tridecapeptide corresponding to the natural NS4A/4B cleavage site; this gave an IC50 of 30 microM, well in agreement with the previously found Km value (40 microM).


Targeting eEF1A by a Legionella pneumophila effector leads to inhibition of protein synthesis and induction of host stress response.
The Legionella pneumophila Dot/Icm type IV secretion system is essential for the biogenesis of a phagosome that supports bacterial multiplication, most likely via the functions of its protein substrates. Recent studies indicate that fundamental cellular processes, such as vesicle trafficking, stress response, autophagy and cell death, are modulated by these effectors. However, how each translocated protein contributes to the modulation of these pathways is largely unknown. In a screen to search substrates of the Dot/Icm transporter that can cause host cell death, we identified a gene whose product is lethal to yeast and mammalian cells. We demonstrate that this protein, called SidI, is a substrate of the Dot/Icm type IV protein transporter that targets the host protein translation process. Our results indicate that SidI specifically interacts with eEF1A and eEF1Bgamma, two components of the eukaryotic protein translation elongation machinery and such interactions leads to inhibition of host protein synthesis. Furthermore, we have isolated two SidI substitution mutants that retain the target binding activity but have lost toxicity to eukaryotic cells, suggesting potential biochemical effect of SidI on eEF1A and eEF1Bgamma. We also show that infection by L. pneumophila leads to eEF1A-mediated activation of the heat shock regulatory protein HSF1 in a virulence-dependent manner and deletion of sidI affects such activation. Moreover, similar response occurred in cells transiently transfected to express SidI. Thus, inhibition of host protein synthesis by specific effectors contributes to the induction of stress response in L. pneumophila-infected cells.


Staphylococcal and streptococcal pyrogenic toxins involved in toxic shock syndrome and related illnesses.
Toxic-shock syndrome (TSS) is an acute onset, multiorgan illness which resembles severe scarlet fever. The illness is caused by Staphylococcus aureus strains that express TSS toxin-1 (TSST-1), enterotoxin B, or enterotoxin C. TSST-1 is associated with menstrual TSS and approximately one-half of nonmenstrual cases; the other two toxins cause nonmenstrual cases, 47% and 3%, respectively. The three toxins are expressed in culture media under similar environmental conditions. These conditions may explain the association of certain tampons with menstrual TSS. Biochemically, the toxins are all relatively low molecular weight and fairly heat and protease stable. Enterotoxins B and C, share nearly 50% sequence homology with streptococcal scarlet fever toxin A; they share no homology with TSST-1 despite sharing numerous biological properties. Numerous animal models for development of TSS have suggested mechanisms of toxin action, though the exact molecular action is not known. The toxins are all potent pyrogens, induce T lymphocyte proliferation, requiring interleukin 1 release from macrophages, suppress immunoglobulin production, enhance endotoxin shock, and enhance hypersensitivity skin reactions. The genetic control of the toxins has been studied and suggests the exotoxins are variable traits. Some additional properties of TSS S. aureus which facilitate disease causation have been clarified.


CaV2 channel subtype expression in rat sympathetic neurons is selectively regulated by α2δ subunits.
Type two voltage gated calcium (CaV2) channels are the primary mediators of neurotransmission at neuronal presynapses, but their function at neural soma is also important in regulating excitability. 1 Mechanisms that regulate CaV2 channel expression at synapses have been studied extensively, which motivated us to perform similar studies in the soma. Rat sympathetic neurons from the superior cervical ganglion (SCG) natively express CaV2.2 and CaV2.3. 2 We noted previously that heterologous expression of CaV2.1 but not CaV2.2 results in increased calcium current in SCG neurons. 3 In the present study, we extended these observations to show that both CaV2.1 and CaV2.3 expression resulted in increased calcium currents while CaV2.2 expression did not. Further, CaV2.1 could displace native CaV2.2 channels, but CaV2.3 expression could not. Heterologous expression of the individual accessory subunits α2δ-1, α2δ-2, α2δ-3, or β4 alone failed to increase current density, suggesting that the calcium current ceiling when CaV2.2 was over-expressed was not due to lack of these subunits. Interestingly, introduction of recombinant α2δ subunits produced surprising effects on displacement of native CaV2.2 by recombinant channels. Both α2δ-1 and α2δ-2 seemed to promote CaV2.2 displacement by recombinant channel expression, while α2δ-3 appeared to protect CaV2.2 from displacement. Thus, we observe a selective prioritization of CaV channel functional expression in neurons by specific α2δ subunits. These data highlight a new function for α2δ subtypes that could shed light on subtype selectivity of CaV2 membrane expression.


Design of the plasma chamber and beam extraction system for SC ECRIS of RAON accelerator.
The RAON accelerator is the heavy ion accelerator being built in Korea. It contains a 3rd generation SC ECRIS which uses 28 GHz/18 GHz microwave power to extract 12 puA uranium ion beams. A plasma chamber for that ECRIS is made of aluminum machined from bulk Al. That chamber contains cooling channels to remove dumped power and another access port for microwave introduction and plasma diagnostics. Beam extraction electrodes were designed considering the engineering issues and preliminary beam extraction analysis was done. That plasma chamber will be assembled with a cryostat, and beam extraction experiment will be done.


Prompt Oseltamivir Therapy Reduces Medical Care and Mortality for Patients With Influenza Infection: An Asian Population Cohort Study.
There are limited population-based studies on the progress of oseltamivir therapy for influenza infection.Using insurance claims data of 2005, 2009, and 2010, the authors established an "in-time" cohort and a "lag-time" cohort representing influenza patients taking the medicine within and not within 1 week to examine the treatment progress. Incident outpatient visit, emergency care and hospitalization, and fatality were compared between the 2 cohorts in the first week and the second week of follow-up periods, after the oseltamivir therapy.A total of 112,492 subjects diagnosed with influenza on oseltamivir therapy in 2005, 2009, and 2010 were identified. The multivariate logistic regression analysis showed that the in-time treatment was superior to the lag-time treatment with less repeat outpatient visits, hospitalizations, and fatality. The overall corresponding in-time treatment to lag-time treatment odds ratios (OR) were 0.50, 0.54, and 0.71 (all P value < 0.05), respectively. The in-time to lag-time ORs of all events were 0.50 in 2009 and 0.54 in 2010.Our study demonstrates that the in-time oseltamivir therapy leads to significantly better treatment outcomes. Oseltamivir should be administered as early as the onset of influenza symptoms appears.


Acyclovir cream for treatment of herpes simplex labialis: results of two randomized, double-blind, vehicle-controlled, multicenter clinical trials.
Acyclovir cream has been available for the treatment of herpes labialis in numerous countries outside the United States for over a decade. Evidence for its efficacy comes from a few small clinical trials conducted in the 1980s. To examine more comprehensively the efficacy and safety of this formulation, we conducted two independent, identical, parallel, randomized, double-blind, vehicle-controlled, large-scale multicenter clinical trials. Healthy adults with a history of frequent herpes labialis were recruited from the general population, screened for eligibility, randomized equally to 5% acyclovir cream or vehicle control, given study medication, and told to self-initiate treatment five times daily for 4 days beginning within 1 h of the onset of a recurrent episode. The number of patients who treated a lesion was 686 in study 1 and 699 in study 2. In study 1, the mean duration of episodes was 4.3 days for patients treated with acyclovir cream and 4.8 days for those treated with the vehicle control (hazards ratio [HR] = 1.23; 95% confidence interval [CI], 1.06 to 1.44; P = 0.007). In study 2, the mean duration of episodes was 4.6 days for patients treated with acyclovir cream and 5.2 days for those treated with the vehicle control (HR = 1.24; 95% CI, 1.06 to 1.44; P = 0.006). Efficacy was apparent whether therapy was initiated "early" (prodrome or erythema lesion stage) or "late" (papule or vesicle stage). There was a statistically significant reduction in the duration of lesion pain in both studies. Acyclovir cream did not prevent the development of classical lesions (progression to vesicles, ulcers, and/or crusts). Adverse events were mild and infrequent.


Perspective: the small bowel examination in the diagnosis of Crohn's disease.
Enteroclysis has been increasingly recommended for radiologic examination of the small intestine, especially for focal lesions, but also for more extensive processes such as regional enteritis. Seventy-four patients were studied who had a final clinical diagnosis of regional enteritis and who had been examined by more conventional peroral ingestion of barium suspension together with fluoroscopy and vigorous manual compression. In only two cases did the radiographic examination fail to identify proven regional enteritis; one who had an isolated ulcer at an ileorectal anastomosis and one in whom jejunal regional enteritis was mistakenly diagnosed as a mesenteric mass. Careful fluoroscopy of the small intestine combined with vigorous manual compression is a sensitive method of detecting regional enteritis.


An overview of disparities and interventions in pediatric kidney transplantation worldwide.
Despite the stated goals of the transplant community and the majority of organ allocation systems, persistent racial disparities in pediatric kidney transplantation exist throughout the world. These disparities are evident in both living and deceased donor kidney transplantation and are independent of any clinical differences between racial groups. The reasons for these persistent disparities are multifactorial, reflecting both patient and provider barriers to care. In this review, we examine the most current findings regarding disparities in pediatric kidney transplantation and consider interventions which may help reduce those disparities.


Informed consent and clinical research involving children and adolescents: implications of the revised APA ethics code and HIPAA.
In 2003, 2 new sets of rules and regulations affecting the conduct of clinical research involving children and adolescents went into effect: the revised American Psychological Association's (APA) Ethical Principles of Psychologists and Code of Conduct (APA, 2002; effective June 1, 2003) and the Privacy Rule (45 CFR Part 160 and A and E of Part 164; effective April; 14, 2003) of the Health Insurance Portability and Accountability Act (HIPAA: Public Law 104-191). This article highlights those APA ethical standards and HIPAA regulations relevant to clinical research involving children and adolescents and discusses how psychologists can apply these rules in ways that will ensure ethical and legal compliance.


Challenges and strategies for investigating the genetic complexity of common human diseases.
There is substantial interest in the identification of genes underlying susceptibility to complex human diseases because of the potential utility of such genes in disease prediction or therapy. Type 1 diabetes is an example of one such disorder and is presumed to arise from the effect of multiple genes and environmental factors. One identified locus has a major effect on type 1 diabetes susceptibility (IDDM1), whereas other loci have significant, yet small, individual effects (IDDM2, IDDM15). It is unclear whether susceptibility for type 1 diabetes arises because of the effects of loci acting independently or whether there are important interactions between loci. Although genetic tools are continuing to be developed to enable examination of candidate regions, the means to identify and narrow "true" susceptibility regions continues to be limited by the lack of statistical power resulting from inadequately sized collections of families. This report provides an evaluation of the approaches for identification of regions harboring type 1 diabetes genes, methods to identify the gene regions that interact to define the risk for type 1 diabetes, and efforts to fine-map the variants responsible.


Spectrum of classes of point emitters of electromagnetic wave fields.
The spectrum of classes of point emitters has been introduced as a numerical tool suitable for the design, analysis, and synthesis of non-paraxial optical fields in arbitrary states of spatial coherence. In this paper, the polarization state of planar electromagnetic wave fields is included in the spectrum of classes, thus increasing its modeling capabilities. In this context, optical processing is realized as a filtering on the spectrum of classes of point emitters, performed by the complex degree of spatial coherence and the two-point correlation of polarization, which could be implemented dynamically by using programmable optical devices.


Bleaching of the red anthocyanin induced by superoxide radical.
Red anthocyanin prepared from petals of Hibiscus rosa-sinensis L. was photobleached in the EDTA-riboflavin system. The rate of bleaching monitored at 565 nm depended on the light intensity and EDTA concentrations. Anaerobic conditions and/or addition of superoxide dismutase prevented the bleaching of anthocyanin, whereas mannitol and catalase did not. A similar bleaching was observed under dark conditions in the xanthine-xanthine oxidase system. The results indicate that anthocyanin is bleached by the nonenzymatic reaction with the superoxide radical and suggest that the pigment can function as an antioxidant. The antioxidative efficiency of cyanidin to superoxide was 10-fold higher than that of cyanidin-3-sophoroside as a Hibiscus anthocyanin.


Medical registrars in 2010: experience and expectations of the future consultant physicians of the UK.
In 2010, 2,176 medical registrars in England (43%) responded to a survey of attitudes to current and future working conditions. Regarding current working, 88% were currently happy with their job with respect to their specialty but only 49% were happy with respect to acute medicine. Even if pay was increased, 59% would only want to work a 48-hour week or less. Regarding future jobs, 59% were worried about future job prospects with 91% exploring ways of extending their training. Only 36% would consider working away from their current location as a consultant, only 42% of those trained in acute medicine wish to take part in the acute take, 15% would consider a 'sub-consultant' post and only 60% were looking forward to becoming a consultant. The findings of this survey show that medical registrars are very concerned about their future. From their perspective, clinical medicine in England is in poor health.


beta3-adrenoceptor control the cystic fibrosis transmembrane conductance regulator through a cAMP/protein kinase A-independent pathway.
In human cardiac myocytes, we have previously identified a functional beta3-adrenoceptor in which stimulation reduces action potential duration. Surprisingly, in cardiac biopsies obtained from cystic fibrosis patients, beta3-adrenoceptor agonists produced no effects on action potential duration. This result suggests the involvement of cystic fibrosis transmembrane conductance regulator (CFTR) chloride current in the electrophysiological effects of beta3-adrenoceptor stimulation in non-cystic fibrosis tissues. We therefore investigated the control of CFTR activity by human beta3-adrenoceptors in a recombinant system: A549 human cells were intranuclearly injected with plasmids encoding CFTR and beta3-adrenoceptors. CFTR activity was functionally assayed using the 6-methoxy-N-(3-sulfopropyl)quinolinium fluorescent probe and the patch-clamp technique. Injection of CFTR-cDNA alone led to the expression of a functional CFTR protein activated by cAMP or cGMP. Co-expression of CFTR (but not of mutated DeltaF508-CFTR) with high levels of beta3-adrenoceptor produced an increased halide permeability under base-line conditions that was not further sensitive to cAMP or beta3-adrenoceptor stimulation. Patch-clamp experiments confirmed that CFTR channels were permanently activated in cells co-expressing CFTR and a high level of beta3-adrenoceptor. Permanent CFTR activation was not associated with elevated intracellular cAMP or cGMP levels. When the expression level of beta3-adrenoceptor was lowered, CFTR was not activated under base-line conditions but became sensitive to beta3-adrenoceptor stimulation (isoproterenol plus nadolol, SR 58611, or CGP 12177). This later effect was not prevented by protein kinase A inhibitors. Our results provide molecular evidence that CFTR but not mutated DeltaF508-CFTR is regulated by beta3-adrenoceptors expression through a protein kinase A-independent pathway.


Addiction, Heroin-Assisted Treatment and the Idea of Abstinence: A reply to Henden.
In our previous article on the question whether heroin addicts are able to give informed consent voluntarily to research on heroin-assisted treatment, we criticized the ongoing bioethical discussion of a flawed conceptualization of heroin addicts' options. As a participant in this discussion, Edmund Henden defends the conceptualization as sufficient for determining whether heroin addicts are able to give informed consent to the research on heroin-assisted treatment voluntarily. This discussion on research on heroin-assisted treatment seems to go astray in several respects. In his reply to our article Henden maintains some of the biases, such as the necessity of abstinence in recovery, that seem to prevail in addiction research on a more general level as well. These biases run the danger of having implausible ethical implications on stakeholders in addiction research and treatment. In our reply to him, we will further clarify and discuss the importance of describing the relevant issues in plausible terms that do justice to the realities of the cases of informed consent in research on heroin-assisted treatment and also raise a wider issue of the ethics of wording as well as of the narrow scope, or 'tunnel vision', in addiction research as currently conducted.


Outcomes of cataract surgery in senile cataract patients at Siriraj Hospital: a prospective observational study.
The present study was done to assess the results of cataract surgery performed in Siriraj Hospital by comparing phacoemulsification and extracapsular cataract extraction techniques in senile cataract patients within a 3-month period. The prospective observational study of a representative sample of 379 patients (409 eyes) who underwent cataract surgery in Siriraj Hospital from January 1, 2004 to March 31, 2004. Identical clinical assessment protocol was used to compare the improvement of postoperative visual acuity and surgical complications between two surgical techniques and different surgeons. Of the 409 eyes, phacoemulsification was performed on 373 eyes (91.2%), and extracapsular cataract extraction was performed on 36 eyes (8.8%). Departmental staff operated on 326 eyes (79.7%) and ophthalmology residents operated on 83 eyes (20.3%). The primary outcome was postoperative visual acuity. Visual acuity was improved > or = 2 Snellen chart lines in 278 of 373 eyes (74.5%) in the phacoemulsification group, and > or = 2 lines in 31 of 36 eyes (86.1%) in the extracapsular cataract extraction group. A small risk of surgical complications was found in the present study. Posterior lens capsule rupture was the most frequent complication found (10/ 409 eyes), followed by corneal injury (9 of 409 eyes). Endophthalmitis was the most severe complication in the present study, occurring in 1 of 409 eyes. There was a significant difference in postoperative visual improvement between phacoemulsification and extracapsular cataract extraction techniques. Final visual acuity in the phacoemulsification group was better than in the extracapsular cataract extraction group.


Genetic structure and population connectivity of the blue and red shrimp Aristeus antennatus.
The blue and red shrimp Aristeus antennatus is a demersal marine species harvested by bottom trawling in the Mediterranean Sea, the adjacent Atlantic Ocean (AO) waters, and the Mozambique Channel in the Indian Ocean (IO). As it is considered to be a priority species for sustainable fishing, identification of its genetic stocks and the connectivity between them is essential. Using 12 microsatellite loci we detected at least four genetic stocks distributed in the Western Mediterranean (WM), Eastern Mediterranean (EM), AO, and IO and signals for a possible fifth stock in the Alborán Sea. We detected no additional population structuring within the WM. Thus, although the Almería-Orán Front exerts some isolating effect, high genetic homogeneity and gene flow are present within the WM Basin. The IO stock is genetically closer to the AO stock than to the others; thus, the species dispersion route is more likely via the Atlantic Ocean than via the Red Sea. Large effective population sizes suggest population sustainability, but moderate genetic diversity values indicate to proceed with caution. Our genetic results serve as a basis for species conservation to ensure long-term sustainability of this marine resource.