Does Transitioning to a Brace Improve HRQoL After Casting for Early Onset Scoliosis?
Serial casting is favored for the initial treatment of early onset scoliosis (EOS), but there is concern about significant morbidity and caregiver burden. Studies have examined the utility of bracing as an alternative to casting, but little is known about differences in health-related quality of life (HRQoL) between treatments. We hypothesized that patients with a diagnosis of idiopathic EOS experience an improvement in HRQoL when transitioning from serial casting to bracing as measured by the 24-Item Early Onset Scoliosis Questionnaire (EOSQ). Subjects with idiopathic EOS were retrospectively identified from a multicenter database. EOSQ scores were compared before treatment, after index casting, after transition out of cast to brace, and at the most recent follow-up. Available major curve magnitudes were also compared during these time points. Data were compared using repeated-measures ANOVA with post hoc Bonferroni correction. Sixty-six subjects met the inclusion criteria. Thirty-seven (56%) subjects were male and the average age at the time of index treatment was 1.9 (0.37-6.4) years. The average follow-up was 3.2 (0.90-6.8) years. In 57 subjects, the major curve magnitude improved from a mean of 33 (CI 28-37) degrees before treatment initiation to 27 (CI 23-30) degrees after casting and to 24 (CI 20-29) degrees at the most recent follow-up. The HRQoL subdomain showed a significant decrease in HRQoL during casting treatment 75.7 (CI 72.9-78.5) from pre-index treatment 84.9 (CI 81.4-88.5), during brace treatment 84.8 (CI 81.8-88.0) and at most recent follow-up 87.0 (CI 83.6-90.3) ( P <0.001). The parental impact subdomain improved from the beginning to the end of treatment (77.7 to 87.7, P =0.001) (n=64). Satisfaction improved from casting to bracing (73.4 to 86.7, P <0.001) (n=63) and to the most recent follow-up (73.4 to 87.9, P <0.001). Patients treated with casting for EOS experience reversible declines in HRQoL. After patients transition from casting to bracing, EOSQ scores recover to pretreatment baseline levels and are maintained at follow-up. This information must be balanced with the effectiveness of treatment for EOS with either method and customized for each patient. Level III-retrospective comparative study.


Removal of NMDA receptor Mg(2+) block extends the action of NT-3 on synaptic transmission in neonatal rat motoneurons.
NT-3 has previously been reported to enhance AMPA/kainate receptor-mediated synaptic responses in motoneurons via an effect on the N-methyl-D-aspartate (NMDA) receptor. To investigate neurotrophin-3 (NT-3) action further, we measured the NMDA receptor (NMDAR)-mediated synaptic response directly by intracellular recording in motoneurons after blocking AMPA/kainate, GABA(A), GABA(B) and glycine receptor-mediated responses pharmacologically. Two pathways were stimulated, the segmental dorsal root (DR) and the descending ventrolateral fasciculus (VLF). The DR-evoked NMDAR-mediated response in motoneurons of rats younger than 1 wk has two components, the initial one of which is generated monosynaptically. NT-3 strongly potentiated both NMDA components in a rapidly reversible manner. No NMDAR-mediated responses were present at VLF connections and at DR connections in older (1- to 2-wk-old) neonates. Bath-applied NT-3-induced potentiation of the AMPA/kainate receptor-mediated response occurred only at connections that exhibit a synaptic NMDA receptor-mediated response. Reducing Mg(2+) concentration in the bathing solution restored the NMDAR-mediated response elicited by DR stimulation in older neonates and by VLF throughout the neonatal period (0-2 wk). In low-Mg(2+), NT-3 enhanced AMPA/kainate receptor-mediated responses elicited by inputs normally not influenced by NT-3. Thus a major reason for the loss of NT-3 action on AMPA/kainate synaptic responses is the reduced activity of the NMDA receptor due to developing Mg(2+) block of NMDA receptor-channel complex as the animal matures, and both can be re-established by reducing Mg(2+) concentration in fluid bathing the spinal cord.


Efficient reduction of nitro compounds and domino preparation of 1-substituted-1H-1,2,3,4-tetrazoles by Pd(ii)-polysalophen coated magnetite NPs as a robust versatile nanocomposite.
A new, versatile, and green methodology has been developed for the efficient NaBH4-reduction of nitroarenes as well as the domino/reduction MCR preparation of 1-substituted-1H-1,2,3,4-tetrazoles using Pd(ii)-polysalophen coated magnetite NPs as an efficient heterogeneous magnetically recyclable nanocatalyst. Polysalophen was firstly prepared based on a triazine framework with a high degree of polymerization, then coordinated to Pd ions and, finally, the resulting hybrid was immobilized on magnetite NPs. The catalyst was characterized by various instrumental and analytical methods, including GPC, DLS, N2 adsorption-desorption, TGA, VSM, TEM, HRTEM, EDX, XPS, XRD, and ICP analyses. The catalyst possesses dual-functionality including the reduction of nitroarenes and the construction of tetrazole rings all in one step via a domino protocol. High to excellent yields were obtained for both nitro reduction and the direct preparation of 1-substituted-1H-1,2,3,4-tetrazoles from nitro compounds. Insight into the mechanism was conducted by XPS in situ as well as DLS in situ along with several control experiments. Recyclability of the catalyst was studied for 6 consecutive runs along with metal leaching measurements in each cycle.


Prevalence and Potential Determinants of COVID-19 Vaccine Hesitancy and Resistance in Qatar: Results from a Nationally Representative Survey of Qatari Nationals and Migrants between December 2020 and January 2021.
Global COVID-19 pandemic containment necessitates understanding the risk of hesitance or resistance to vaccine uptake in different populations. The Middle East and North Africa currently lack vital representative vaccine hesitancy data. We conducted the first representative national phone survey among the adult population of Qatar, between December 2020 and January 2021, to estimate the prevalence and identify potential determinants of vaccine willingness: acceptance (strongly agree), resistance (strongly disagree), and hesitance (somewhat agree, neutral, somewhat disagree). Bivariate and multinomial logistic regression models estimated associations between willingness groups and fifteen variables. In the total sample, 42.7% (95% CI: 39.5-46.1) were accepting, 45.2% (95% CI: 41.9-48.4) hesitant, and 12.1% (95% CI: 10.1-14.4) resistant. Vaccine resistant compared with hesistant and accepting groups reported no endorsement source will increase vaccine confidence (58.9% vs. 5.6% vs. 0.2%, respectively). Female gender, Arab ethnicity, migrant status/type, and vaccine side-effects concerns were associated with hesitancy and resistance. COVID-19 related bereavement, infection, and quarantine status were not significantly associated with any willingness group. Absence of or lack of concern about contracting the virus was solely associated with resistance. COVID-19 vaccine resistance, hesitance, and side-effects concerns are high in Qatar's population compared with those globally. Urgent public health engagement should focus on women, Qataris (non-migrants), and those of Arab ethnicity.


Factors affecting the in vitro production of volatile fatty acids by mixed bacterial populations from the bovine rumen.
Factors affecting in vitro ruminal bacterial VFA production were examined. Treatments consisted of high and low initial pH (6.7, 5.7), osmolality (600, 400 mOsm) and concentrations of acetic (40, 0 mM) and propionic acids (20, 0 mM). Response variables measured included the production of acetic, propionic and total VFA, total gas and methane. Initial pH affected (P less than .05) most variables either independently or in combination with one or more of the other factors. Acetic acid production was reduced 40% (P = .03) when initial acetic acid concentrations were 40 mM compared with 0 mM. Also, acetic acid production was less (P less than .01) at low initial pH (5.7) than at high initial pH (6.7). Propionic acid production was greater (P = .05) at high vs low initial acetic acid concentrations. Propionic acid production was greater in response to low vs high initial osmolality, although the magnitude of this difference depended on initial pH (interaction P = .02). Total production of VFA was greater (P less than .01) at high than at low initial pH; however, at low initial pH, no difference (P greater than .05) was observed due to initial osmolality, whereas at high pH, production was greater (interaction P = .04) for low than for high initial osmolality. The diminished production of total VFA at pH 5.7 occurred primarily due to reduced acetic acid production, although increased production of propionic and butyric acids was noted.(ABSTRACT TRUNCATED AT 250 WORDS)


Antinociceptive and free radical scavenging activities of alkaloids isolated from Lindera angustifolia Chen.
Lindera angustifolia Chen is a folk medicine used for the treatment of contusions-induced swelling, rheumatic pains and bellyache in south and the middle part of China. Phytochemical studies showed that aporphine and benzyltetrahydroisoquinoline alkaloids are the characteristic constituents of this plant. In this study, we evaluated the antinociceptive and free radical scavenging properties of six aporphine and two benzyltetrahydroisoquinoline alkaloids isolated from the root of Lindera angustifolia. All alkaloids except magnocurarine exhibited remarkable radical scavenging effects (36-90% scavenging at 25-100microg/ml) in DPPH radical scavenging test, among them norisocorydine showed the hightest activity (SC(50): 14.1microg/ml). Antinociceptive activities were tested by using acetic acid-induced writhing and formalin test at dose of 20mg/kg. Norisocorydine exhibited the highest antinociceptive ability with 83.5% writhing inhibition. Boldine, norboldine showed significant antinociceptive activity with 76.3% and 74.6% writhing inhibition respectively. Indomethacin was used as positive control, which showed 67.8% writhing inhibition at dose of 10mg/kg. Most of the compounds, except N-ethoxycarbonyllaurotetanine and magnocurarine, could significantly inhibit the phase I reaction (P<0.01), and all of them inhibited the phase II reaction (P<0.001) in the formalin tests (indomethacin and morphine were used as positive drugs). The antinociceptive effects exhibited a structure-activity relationship similar to that of the free radical scavenging activities. Above results suggested that the alkaloids from the root of Lindera angustifolia possess both free radical scavenging and antinociceptive activities, and the antinociceptive activity seems to be related to the free radical scavenging effect.


A Review of Driving and Binocularity.
Although most jurisdictions allow stereoscopically deficient and monocular individuals to drive, studies regarding these visual components' effects on driving have to date yielded contradicting results. Interviews, record reviews, and experiments have been used to unmask these effects. In interviews, participants with amblyopia reported several difficulties operating automobiles. Record reviews yielded mixed results, with studies revealing an increased crash rate and/or severity in a group of stereoscopically deficient commercial drivers, whereas studies of non-commercial drivers failed to make that association. Furthermore, experimental studies showed that individuals with reduced stereopsis braked earlier and were less likely to crash. With regard to monocularity, real-life experiments failed to demonstrate a poorer driving performance and simulation studies showed that drivers with sudden monocularity were more likely to crash and drive off the road. [J Pediatr Ophthalmol Strabismus. 2022;59(1):6-12.].


Mannitol Metabolism in Lentinus edodes, the Shiitake Mushroom.
Mannitol metabolism was evaluated in fruiting bodies of Lentinus edodes. Cell extracts were prepared from fruiting bodies, and key enzymes involved in mannitol metabolism were assayed, including hexokinase, mannitol dehydrogenase, mannitol-1-phosphate dehydrogenase, mannitol-1-phosphatase, and fructose-6-phosphatase. Mannitol dehydrogenase, fructose-6-phosphatase, mannitol-1-phosphatase, and hexokinase activities were found in extracts of fruiting bodies. However, mannitol-1-phosphate dehydrogenase activity was not detected. Mycelial cultures were grown in an enriched liquid medium, and enzymes of the mannitol cycle were assayed in cell extracts of rapidly growing cells. Mannitol-1-phosphate dehydrogenase activity was also not found in mycelial extracts. Hence, evidence for a complete mannitol cycle both in vegetative mycelia and during mushroom development was lacking. The pathway of mannitol synthesis in L. edodes appears to utilize fructose as an intermediate.


From state care to self-care: cancer screening behaviours among Russian-speaking Australian women.
In this article, we report on a small qualitative scale study with immigrant Russian-speaking Australian women, carers of dependent family members. Drawing on in-depth interviews, we explore women's health-related behaviours, in particular their participation in breast and cervical cancer screening. Differences in preventive health care policies in country of origin and Australia explain their poor participation in cancer screening. Our participants had grown up in the former Soviet Union, where health checks were compulsory but where advice about frequency and timing was the responsibility of doctors. Following migration, women continued to believe that the responsibility for checks was their doctor's, and they maintained that, compared with their experience of preventive medicine in the former Soviet Union, Australian practice was poor. Women argued that if reproductive health screening were important in cancer prevention, then health care providers would take a lead role to ensure that all women participated. Data suggest how women's participation in screening may be improved.


Effect of L-serine on the biosynthesis of aromatic amino acids in Escherichia coli.
It is well known that some amino acids inhibit bacterial growth. L-Serine is known to inhibit the growth of Escherichia coli by inhibition of homoserine dehydrogenase (EC 220.127.116.11). It has been reported that this L-serine inhibition may be prevented by the addition of L-isoleucine or L-threonine to the medium. In our study, however, recovery of the growth inhibition of Escherichia coli by L-serine occurred in the presence of several amino acids, especially L-phenylalanine. In an attempt to further elucidate this inhibition mechanism, different intermediates of aromatic amino acid biosynthesis were added to the growth medium. Recovery from the inhibition did not occur in the presence of prephenate but did occur when phenylpyruvate was added to the medium. The specific activity of prephenate dehydratase decreased in cells grown in the presence of L-serine. However. L-serine did not inhibit in vitro prephenate dehydratase activity, and the expression of pheA, which encodes the prephenate dehydratase, was not depressed by L-serine. We suggest that L-serine acts via another inhibition mechanism. Although this inhibition mechanism has not been fully elucidated, our results suggest that the addition of L-serine to the growth medium inhibits prephenate dehydratase synthesis and thus affects L-phenylalanine biosynthesis.


The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-4-binding residues.
The four mammalian SPRY domain-containing SOCS box proteins (SSB-1 to SSB-4) are characterized by a C-terminal SOCS box and a central SPRY domain. We have determined the first SPRY-domain structure, as part of SSB-2, by NMR. This domain adopts a novel fold consisting of a beta-sandwich structure formed by two four-stranded antiparallel beta-sheets with a unique topology. We demonstrate that SSB-1, SSB-2 and SSB-4, but not SSB-3, bind prostate apoptosis response protein-4 (Par-4). Mutational analysis of SSB-2 loop regions identified conserved structural determinants for its interaction with Par-4 and the hepatocyte growth factor receptor, c-Met. Mutations in analogous loop regions of pyrin and midline-1 SPRY domains have been shown to cause Mediterranean fever and Opitz syndrome, respectively. Our findings provide a template for SPRY-domain structure and an insight into the mechanism of SPRY-protein interaction.


Factors Influencing Global Health Related Quality of Life in Elderly Cancer Patients: Results of a Secondary Data Analysis.
Cancer treatment for elderly patients is often complicated by poor physical condition, impaired functioning and comorbidities. Patient reported health related quality of life (HRQOL) can contribute to decisions about treatment goals and supportive therapy. Knowledge about factors influencing HRQOL is therefore needed for the development of supportive measures and care pathways. An exploratory secondary data analysis on 518 assessments of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire (EORTC QLQ-C30) and the elderly module (EORTC QLQ-ELD14) was performed to identify factors predictive for global HRQOL. Preliminary simple and multivariable regression analyses were conducted resulting in a final model comprising sociodemographic and disease specific variables and scales of the QLQ-C30 and QLQ-ELD14. Age, sex and disease related variables explained only part of the variance of global HRQOL (adjusted R2 = 0.203). In the final model (adjusted R2 = 0.504) fatigue, social function, burden of illness and joint stiffness showed possible influence on global HRQOL. Fatigue, social function and burden of illness seem to have the largest impact on global HRQOL of elderly cancer patients. Further prospective studies should examine these domains. Actionable symptoms should be given special attention to initiate targeted supportive measures aiming to maximize HRQOL of older cancer patients.


Early administration of surfactant via a thin intratracheal catheter in preterm infants with respiratory distress syndrome: Feasibility and outcome.
Currently, the method of early nasal continuous positive airway pressure (nCPAP) and selective administration of surfactant via an endotracheal tube is widely used in the treatment of respiratory distress syndrome (RDS) in premature infants. To prevent complications related to endotracheal intubation and even a brief period of mechanical ventilation, in this study, we compared the effectiveness of surfactant administration via a thin intratracheal catheter versus the current method using an endotracheal tube. Thirty eight preterm infants ≤34 weeks' gestation with birth weight of 1000-1800 g who were putted on nCPAP for RDS within the first hour of life, were randomly assigned to receive surfactant either via endotracheal tube (ET group) or via thin intratracheal catheter (CATH group). The primary outcomes were the need for mechanical ventilation and duration of oxygen therapy. Data were analyzed by independent t-test, Mann-Whitney U-test, and Chi-square test, using SPSS v. 21. There was no significant difference between groups regarding to need for mechanical ventilation during the first 72 h of birth (3 [15.8%] in ET group vs. 2 [10.5%] in CATH group; P = 0.99). Duration of oxygen therapy in CATH group was significantly lower than ET group (243.7 ± 74.3 h vs. 476.8 ± 106.8 h, respectively; P = 0.018). The incidence of adverse events during all times of surfactant administration was not statistically significant between groups (P = 0.14), but the number of infants who experienced adverse events during surfactant administration was significantly lower in CATH group than ET group (6 [31.6%] vs. 12 [63.2%], respectively; P = 0.049). All other outcomes, including duration of treatment with CPAP and mechanical ventilation, times of surfactant administration and the need for more than one dose of the drug, the rate of intraventricular hemorrhage, mortality and combined outcome of chronic lung disease or mortality were statistically similar between the groups. Surfactant administration via thin intratracheal catheter in preterm infants receiving nCPAP for treatment of RDS has similar efficacy, feasibility and safety to its administration via endotracheal tube.


Tridimensional acculturation and adaptation among Jamaican adolescent-mother dyads in the United States.
A bidimensional acculturation framework cannot account for multiple destination cultures within contemporary settlement societies. A tridimensional model is proposed and tested among Jamaican adolescent-mother dyads in the United States compared to Jamaican Islander, European American, African American, and other Black and non-Black U.S. immigrant dyads (473 dyads, M adolescent age = 14 years). Jamaican immigrants evidence tridimensional acculturation, orienting toward Jamaican, African American, and European American cultures. Integration is favored (70%), particularly tricultural integration; moreover, Jamaican and other Black U.S. immigrants are more oriented toward African American than European American culture. Jamaican immigrant youth adapt at least as well as nonimmigrant peers in Jamaica and the United States. However, assimilated adolescents, particularly first generation immigrants, have worse sociocultural adaptation than integrated and separated adolescents.


Immunomodulation for the management of severe SARS-CoV2 infections. State of the art and review of the literature.
This Mini Review of the literature aimed to assess the role of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19). Based on the available scientific evidence, it is not clear to date what is the best therapeutic strategy for the treatment of COVID-19. Since SARS-CoV-2 infection stimulates a vigorous proinflammatory response and may cause the so-called "cytokine storm", immunomodulator drugs have been investigated as potential treatment for severe COVID-19 pneumonia. Among immunomodulators, tocilizumab, a recombinant humanized monoclonal antibody directed against IL-6 receptor, seems to be promising. An increasing number of clinical trials are exploring the role of tocilizumab in COVID-19, focusing on outcomes like mortality, risk of intensive care unit admission and the need for mechanical ventilation. At the moment, there is no conclusive evidence that tocilizumab would be proper outright in all patients with COVID-19 pneumonia, but some studies suggest that its use may be beneficial in selected categories of patients.


Stroke evaluation and treatment.
Cerebrovascular accidents remain the third leading cause of death in the United States, with many left with life-long disabilities. The causes and contributing factors of stroke are beginning to be well defined, but what is not appreciated are the various techniques for assisting recovery. Understanding what parts of the neurological and musculoskeletal exams predict short-term and long-term disabilities helps guide patients and families. Newer and effective rehabilitative approaches are available as are home, outpatient, and hospital-based sites for recovery. Improvements after stroke are now recognized to continue for months to years after the event. Available therapeutic techniques and evaluative studies are presented in this review.


Vanadium-Substituted Phosphomolybdic Acids for the Aerobic Cleavage of Lignin Models-Mechanistic Aspect and Extension to Lignin.
This work deals with the aerobic oxidative cleavage of C-C and C-O bonds catalyzed by the Keggin-type phosphovanadomolybdic acid (H6[PMo9V3O40], noted H6PV3). The latter was synthesized by an adapted hydrothermal procedure classically used for lower vanadium content and was tested as a catalyst for the aerobic cleavage of 2-phenoxyacetophenone (noted K1HH) and 1-phenyl-2-phenoxyethanol (A1HH) used as two lignin models. The operative conditions (solvent, catalytic loading, etc.) were adjusted on K1HH and extrapolated to A1HH. The cleavage of the alcohol model required more drastic conditions and therefore further optimization. Preliminary attempts on an Organosolv wheat straw lignin were performed too. From the kinetic study, high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) data, a mechanism of the cleavage of both models was proposed.


Consistency of fish-shoal social network structure under laboratory conditions.
We investigated the consistency of association network structure for groups of sticklebacks Gasterosteus aculeatus. Each group was observed twice and we varied the duration between observations and the size of the experimental arena that they were observed in. At the dyad level, we found positive correlations between dyad interaction frequencies across observations. At the group level we found variation in four network metrics between observations, but only in treatments where the duration between observations was short. Specifically, fish formed more and smaller groups in the second observation in this treatment. Fish were also organized into more subunits in the larger arenas. Finally, we saw positive correlations between some group network metrics across observations suggesting relative consistency at the group level. There are several processes that might drive these interaction patterns. Our findings have implications for experimental design and the comparison and integration of findings of experiments from different studies carried out under different conditions.


Cannabinoid Signaling in Cancer.
The family of chemical structures that interact with a cannabinoid receptor are broadly termed cannabinoids. Traditionally known for their psychotropic effects and their use as palliative medicine in cancer, cannabinoids are very versatile and are known to interact with several orphan receptors besides cannabinoid receptors (CBR) in the body. Recent studies have shown that several key pathways involved in cell growth, differentiation and, even metabolism and apoptosis crosstalk with cannabinoid signaling. Several of these pathways including AKT, EGFR, and mTOR are known to contribute to tumor development and metastasis, and cannabinoids may reverse their effects, thereby by inducing apoptosis, autophagy and modulating the immune system. In this book chapter, we explore how cannabinoids regulate diverse signaling mechanisms in cancer and immune cells within the tumor microenvironment and whether they impart a therapeutic effect. We also provide some important insight into the role of cannabinoids in cellular and whole body metabolism in the context of tumor inhibition. Finally, we highlight recent and ongoing clinical trials that include cannabinoids as a therapeutic strategy and several combinational approaches towards novel therapeutic opportunities in several invasive cancer conditions.


Antifibrinolytics for heavy menstrual bleeding.
Heavy menstrual bleeding (HMB) is an important physical and social problem for women. Oral treatment for HMB includes antifibrinolytic drugs, which are designed to reduce bleeding by inhibiting clot-dissolving enzymes in the endometrium.Historically, there has been some concern that using the antifibrinolytic tranexamic acid (TXA) for HMB may increase the risk of venous thromboembolic disease. This is an umbrella term for deep venous thrombosis (blood clots in the blood vessels in the legs) and pulmonary emboli (blood clots in the blood vessels in the lungs). To determine the effectiveness and safety of antifibrinolytic medications as a treatment for heavy menstrual bleeding. We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO and two trials registers in November 2017, together with reference checking and contact with study authors and experts in the field. We included randomized controlled trials (RCTs) comparing antifibrinolytic agents versus placebo, no treatment or other medical treatment in women of reproductive age with HMB. Twelve studies utilised TXA and one utilised a prodrug of TXA (Kabi). We used standard methodological procedures expected by Cochrane. The primary review outcomes were menstrual blood loss (MBL), improvement in HMB, and thromboembolic events. We included 13 RCTs (1312 participants analysed). The evidence was very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding, and poor reporting of study methods), imprecision and inconsistency.Antifibrinolytics (TXA or Kabi) versus no treatment or placeboWhen compared with a placebo, antifibrinolytics were associated with reduced mean blood loss (MD -53.20 mL per cycle, 95% CI -62.70 to -43.70; I² = 8%; 4 RCTs, participants = 565; moderate-quality evidence) and higher rates of improvement (RR 3.34, 95% CI 1.84 to 6.09; 3 RCTS, participants = 271; moderate-quality evidence). This suggests that if 11% of women improve without treatment, 43% to 63% of women taking antifibrinolytics will do so. There was no clear evidence of a difference between the groups in adverse events (RR 1.05, 95% CI 0.93 to 1.18; 1 RCT, participants = 297; low-quality evidence). Only one thromboembolic event occurred in the two studies that reported this outcome.TXA versus progestogensThere was no clear evidence of a difference between the groups in mean blood loss measured using the Pictorial Blood Assessment Chart (PBAC) (MD -12.22 points per cycle, 95% CI -30.8 to 6.36; I² = 0%; 3 RCTs, participants = 312; very low quality evidence), but TXA was associated with a higher likelihood of improvement (RR 1.54, 95% CI 1.31 to 1.80; I² = 32%; 5 RCTs, participants = 422; low-quality evidence). This suggests that if 46% of women improve with progestogens, 61% to 83% of women will do so with TXA.Adverse events were less common in the TXA group (RR 0.66, 95% CI 0.46 to 0.94; I² = 28%; 4 RCTs, participants = 349; low-quality evidence). No thromboembolic events were reported in any group.TXA versus non-steroidal anti-inflammatory drugs (NSAIDs)TXA was associated with reduced mean blood loss (MD -73.00 mL per cycle, 95% CI -123.35 to -22.65; 1 RCT, participants = 49; low-quality evidence) and higher likelihood of improvement (RR 1.43, 95% CI 1.18 to 1.74; 12 = 0%; 2 RCTs, participants = 161; low-quality evidence). This suggests that if 61% of women improve with NSAIDs, 71% to 100% of women will do so with TXA. Adverse events were uncommon and no comparative data were available. No thromboembolic events were reported.TXA versus ethamsylateTXA was associated with reduced mean blood loss (MD 100 mL per cycle, 95% CI -141.82 to -58.18; 1 RCT, participants = 53; low-quality evidence), but there was insufficient evidence to determine whether the groups differed in rates of improvement (RR 1.56, 95% CI 0.95 to 2.55; 1 RCT, participants = 53; very low quality evidence) or withdrawal due to adverse events (RR 0.78, 95% CI 0.19 to 3.15; 1 RCT, participants = 53; very low quality evidence).TXA versus herbal medicines (Safoof Habis and Punica granatum)TXA was associated with a reduced mean PBAC score after three months' treatment (MD -23.90 pts per cycle, 95% CI -31.92 to -15.88; I² = 0%; 2 RCTs, participants = 121; low-quality evidence). No data were available for rates of improvement. TXA was associated with a reduced mean PBAC score three months after the end of the treatment phase (MD -10.40 points per cycle, 95% CI -19.20 to -1.60; I² not applicable; 1 RCT, participants = 84; very low quality evidence). There was insufficient evidence to determine whether the groups differed in rates of adverse events (RR 2.25, 95% CI 0.74 to 6.80; 1 RCT, participants = 94; very low quality evidence). No thromboembolic events were reported.TXA versus levonorgestrel intrauterine system (LIUS)TXA was associated with a higher median PBAC score than TXA (median difference 125.5 points; 1 RCT, participants = 42; very low quality evidence) and a lower likelihood of improvement (RR 0.43, 95% CI 0.24 to 0.77; 1 RCT, participants = 42; very low quality evidence). This suggests that if 85% of women improve with LIUS, 20% to 65% of women will do so with TXA. There was insufficient evidence to determine whether the groups differed in rates of adverse events (RR 0.83, 95% CI 0.25 to 2.80; 1 RCT, participants = 42; very low quality evidence). No thromboembolic events were reported. Antifibrinolytic treatment (such as TXA) appears effective for treating HMB compared to placebo, NSAIDs, oral luteal progestogens, ethamsylate, or herbal remedies, but may be less effective than LIUS. There were too few data for most comparisons to determine whether antifibrinolytics were associated with increased risk of adverse events, and most studies did not specifically include thromboembolism as an outcome.


Not all errors are the same: ERP sensitivity to error typicality in foreign accented speech perception.
Intercultural communication has become more and more frequent in the recent globalized society. When native listeners try to understand non-native speakers, they have to deal with different types of grammatical errors, some being frequently encountered and others being less common. The present Event-Related Potential (ERP) study investigated how native listeners process different types of morphosyntactic errors in foreign accented speech and whether they are sensitive to error typicality. Spanish natives listened to Spanish sentences in native and foreign (English) accent. ERPs were recorded in response to morphosyntactic violations that were commonly (gender errors) encountered in English accented Spanish or not (number errors). Although sentence comprehension accuracy did not differ across accents, the ERP responses changed as a function of accent and error type. In line with previous studies, gender and number violations in native accented speech elicited LAN-P600 responses. When speech was uttered by foreign speakers, number violations (uncommon errors) showed a P600 effect, while gender violations (common errors) did not elicit late repair processes (reflected by the P600) but an N400 effect. The present results provide evidence that the neural time course of parsing depends not only on speaker's accent, but also on input error typicality.


From macroscopic mechanics to cell-effective stiffness within highly aligned macroporous collagen scaffolds.
In the design of macroporous biomaterial scaffolds, attention is payed predominantly to the readily accessible macroscopic mechanical properties rather than to the mechanical properties experienced by the cells adhering to the material. However, the direct cell mechanical environment has been shown to be of special relevance for biological processes such as proliferation, differentiation and extracellular matrix formation both in vitro and in vivo. In this study we investigated how individual architectural features of highly aligned macroporous collagen scaffolds contribute to its mechanical properties on the macroscopic vs. the microscopic scale. Scaffolds were produced by controlled freezing and freeze-drying, a method frequently used for manufacturing of macroporous biomaterials. The individual architectural features of the biomaterial were carefully characterized to develop a finite element model (FE-model) that finally provided insights in the relation between the biomaterial's mechanical properties on the macro-scale and the properties on the micro-scale, as experienced by adhering cells. FE-models were validated by experimental characterization of the scaffolds, both on the macroscopic and the microscopic level, using mechanical compression testing and atomic force microscopy. As a result, a so-called cell-effective stiffness of these non-trivial scaffold architectures could be predicted for the first time. A linear dependency between the macroscopic scaffold stiffness and the cell-effective stiffness was found, with the latter being consistently higher by a factor of 6.4 ± 0.6. The relevance of the cell-effective stiffness in controlling progenitor cell differentiation was confirmed in vitro. The obtained information about the cell-effective stiffness is of particular relevance for the early stages of tissue regeneration, when the cells first populate and interact with the biomaterial. Beyond the specific biomaterial investigated here, the introduced method is transferable to other complex biomaterial architectures. Design-optimization in 3D macroporous scaffolds that are based on a deeper understanding of the mechanical environment provided to the cells will help to enhance biomaterial-based tissue regeneration approaches.


Clinical Significance of Claudin Expression in Oral Squamous Cell Carcinoma.
A change in claudin expression has been demonstrated in various tumors. The present study specifically compares claudin expression in oral squamous cell carcinoma (OSCC) with healthy oral epithelium from the same individual and analyzes the association between claudin expression and the clinically relevant course parameters. Our study includes tissue samples and clinically relevant follow-up data from 60 patients with primary and untreated OSCC. The oral mucosa was analyzed via Western blot for the expression of claudin-1, -2, -3, -4, -5, and -7. Importantly, the tumor and healthy tissues were obtained pairwise from patients, allowing for intraindividual comparisons. Both the healthy and tumor epithelium from the oral cavity did not express the claudin-3 protein. The intraindividual comparison revealed that, in OSCC, claudin-2 expression was higher, and the expression of claudin-4, -5, and -7 was lower than in healthy epithelium. An association was found between increased claudin-2 expression and shorter relapse-free survival. In addition, the reduced expression of claudin-4 had a negative impact on relapse-free survival. Furthermore, associations between the reduced expression of claudin-7 and the stage of a tumor, or the presence of lymph node metastases, were found. Thus, the expression level of claudin-2, -4, and -7 appears to be predictive of the diagnosis and prognosis of OSCC.


Education of speech-language pathologists and audiologists in Brazil.
The field of speech-language pathology (SLP) in Brazil, named 'fonoaudiologia', comprises both a therapeutic approach to communication disorders and audiology and was officially recognized on December 9, 1981 (law No. 6965). University programs exist since the 1960s. The undergraduate level is a 4-year honors Bachelor of Science program and requires at least a 3,700 h of coursework. Since 1996 four areas of specialization were established: language, audiology, voice and oral myology, requiring a minimum of 500 h of course. Graduate programs in the narrower sense,master's degree and doctorate, exist since the 1970s. Brazil is a 180-million inhabitant country with approximately 25,000 speech-language pathologists, of which 2,700 are specialists, 800 masters and 210 doctors. There are almost 100 undergraduate programs and 70 specialization courses; however, for master's degree and doctorate purposes there are only 8.


Foliar application of putrescine alleviates terminal drought stress by modulating water status, membrane stability, and yield- related traits in wheat (Triticum aestivum L.).
Drought stress is one of the major limitations to the growth and yield productivity of cereal crops. It severely impairs the early growing and grain -filling stages of wheat. Therefore, cost- effective and eco-friendly approaches for alleviating drought stress in cereal crops are in high demand. Polyamines, such as putrescine, have a significant effect on improving crop yield under drought- stress conditions. Therefore, the current study was executed with the aim of exploring the significance of putrescine in alleviating drought stress and improving yield- related traits in wheat. Two distinct wheat cultivars (Fakhar-e-Bhakkar and Anaj-2017) were treated with the foliar application of different concentrations (control, 0.5, 1.0, and 1.5 PPM) of putrescine (put) under two moisture conditions (well- watered and terminal drought stress). The results demonstrate that the imposition of terminal drought stress significantly reduces different physiological and yield- related traits of both wheat cultivars. The reduction of relative water content (RWC%), membrane stability index (MSI), leaf area, tillers per plant, biomass yield, number of spikelets per spike, 100-grain weight, grain yield per plant, and straw yield was greater in Anaj-2017 than in Fakhar-e-Bhakkar cultivar. The results further explain that the foliar application of increased concentrations of putrescine from 0.0 to 1.0 PPM gradually improved physiological and yield traits, whereas these traits declined with the application of putrescine at the highest dose (1.5 PPM). The exogenous application of 1.0 PPM putrescine improved the relative water content (19.76%), specific leaf area (41.47%), and leaf area ratio (35.84%) compared with the controlled treatment. A higher grain yield (28.0 g plant-1) and 100-grain weight (3.8 g) were obtained with the foliar application of 1.0 PPM putrescine compared with controlled treatments. The findings of this study confirm the protective role of putrescine against terminal drought stress. It is therefore recommended to use putrescine at a concentration of 1.0 PPM, which could help alleviate terminal drought stress and attain better wheat yield.


Strengthening Emotional Development and Emotion Regulation in Childhood-As a Key Task in Early Childhood Education.
The following article deals with emotional development and the development of emotion regulation skills in children during early childhood education, focusing primarily on the importance of the early childhood teacher. Emotion regulation is important for success and wellbeing in further life. It is developed in interaction with parents as attachment figures. Teachers can also be important persons for the child in the context of bonding. This leads to the question of how early childhood teachers can support children learning to regulate their emotions. We analyze with the content analysis, four programs for promoting social and emotional skills that are currently used in Germany. The main question is if the programs include elements that increase teachers' skills in supporting the children in regulating their emotions. The categories to analyze the programs are derived from theories of teacher-child interaction. In addition to programs for promoting emotional and social development, we will discuss aspects of shaping interaction as essential elements in promoting emotion regulation. The conclusion outlines some key implications for educational practice and the importance of developing professional behavior for qualitative teacher-child interactions.


Development of composite outcomes for individual patient data (IPD) meta-analysis on the effects of diet and lifestyle in pregnancy: a Delphi survey.
To develop maternal, fetal, and neonatal composite outcomes relevant to the evaluation of diet and lifestyle interventions in pregnancy by individual patient data (IPD) meta-analysis. Delphi survey. The International Weight Management in Pregnancy (i-WIP) collaborative network. Sample Twenty-six researchers from the i-WIP collaborative network from 11 countries. A two-generational Delphi survey involving members of the i-WIP collaborative network (26 members in 11 countries) was undertaken to prioritise the individual outcomes for their importance in clinical care. The final components of the composite outcomes were identified using pre-specified criteria. Composite outcomes considered to be important for the evaluation of the effect of diet and lifestyle in pregnancy. Of the 36 maternal outcomes, nine were prioritised and the following were included in the final composite: pre-eclampsia or pregnancy-induced hypertension, gestational diabetes mellitus (GDM), elective or emergency caesarean section, and preterm delivery. Of the 27 fetal and neonatal outcomes, nine were further evaluated, with the final composite consisting of intrauterine death, small for gestational age, large for gestational age, and admission to a neonatal intensive care unit (NICU). Our work has identified the components of maternal, fetal, and neonatal composite outcomes required for the assessment of diet and lifestyle interventions in pregnancy by IPD meta-analysis.


Laser therapy reduces gelatinolytic activity in the rat trigeminal ganglion during temporomandibular joint inflammation.
To investigate whether low-level laser therapy (LLLT) alters the expression and activity of MMP-2 and MMP-9 in the trigeminal ganglion (TG) during different stages of temporomandibular joint (TMJ) inflammation in rats. It also evaluated whether LLLT modifies mechanical allodynia and orofacial hyperalgesia. Wistar rats (±250 g) were divided into groups that received saline (SAL) or complete Freund's adjuvant (CFA, 50 μl) in the TMJ, and that later underwent LLLT (20 J cm(-2) ) at their TMJ or not (groups SAL, SAL + LLLT, CFA, and CFA + LLLT). LLLT was applied on days 3, 5, 7, and 9 after SAL or CFA. Mechanical allodynia was evaluated on days 1, 3, 5, 7, and 10; orofacial hyperalgesia was assessed on day 10. Gelatin zymography and in situ zymography aided quantification of MMPs in the TG. Low-level laser therapy abolished the reduction in the mechanical orofacial threshold and the increase in orofacial rubbing during the orofacial formalin test induced by CFA. LLLT also decreased the CFA-induced rise in the levels of MMP-9 and MMP-2 as well as the gelatinolytic activity in the TG. Low-level laser therapy could constitute an adjuvant therapy to treat temporomandibular disorders and prevent inflammation-induced alterations in the levels of MMP-2 and MMP-9 and in the gelatinolytic activity in TGs.


Single amino acid mutations in the cadherin receptor from Heliothis virescens affect its toxin binding ability to Cry1A toxins.
Bacillus thuringiensis Cry protein exerts its toxic effect through a receptor-mediated process. Both aminopeptidases and cadherin proteins were identified as putative Cry1A receptors from Heliothis virescens and Manduca sexta. The importance of cadherin was implied by its correlation with a Cry1Ac resistant H. virescens strain (Gahan, L. J., Gould, F., and Heckel, D. G. (2001) Science 293, 857-860). In this study, the Cry1Ac toxin-binding region in H. virescens cadherin was mapped to a 40-amino-acid fragment, from amino acids 1422 to 1440. This site overlaps with a Cry1Ab toxin-binding site, amino acids 1363-1464 recently reported in M. sexta (Hua, G., Jurat-Fuentes, J. L., and Adang, M. J. (2004) J. Biol. Chem. 279, 28051-28056). Further, feeding of the anti-H. virescens cadherin antiserum or the partial cadherins, which contain the toxin-binding region, in combination with Cry1Ab/Cry1Ac reduced insect mortality by 25.5-55.6% to first instar H. virescens and M. sexta larvae, suggesting a critical function for this cadherin domain in insect toxicity. Mutations in this region, to which the Cry1Ac binds through its loop 3, resulted in the loss of toxin binding. For the first time, we show that the cadherin amino acids Leu(1425) and Phe(1429) are critical for Cry1Ac toxin interaction, and if substituted with charged amino acids, result in the loss of toxin binding, with a K(D) of < 10(-5) m. Mutation of Gln(1430) to an alanine, however, increased the Cry1Ac affinity 10-fold primarily due to an increase on rate. The L1425R mutant can result from a single nucleotide mutation, CTG --> CGG, suggesting that these mutants, which have decreased toxin binding, may lead to Cry1A resistance in insects.


Strategies to harness immunity against infectious pathogens after haploidentical stem cell transplantation.
Viral and fungal infections account for significant morbidity and mortality, particularly in pediatric patients with profound immune suppression resulting from allogeneic hematopoietic stem cell transplantation (HSCT). Therapies with anti-viral and anti-fungal drugs are often associated with significant toxicity, are of limited efficacy and can induce drug resistance. One innovative approach to prevent and/or treat viral and fungal infections involves the adoptive transfer of in vitro-expanded or in vitro-generated pathogen-specific T cells. This review summarizes the clinical trials that have been run to date with virus- and fungus-specific T cells, with special emphasis on the clinical context of haploidentical HSCT for pediatric malignancies. It will also discuss initiatives and strategies to overcome the hurdles associated with time-consuming and complex GMP-grade laboratory procedures required to generate pathogen-specific T cells.


[Clinical application and long-term results of stapling device in rectal carcinoma].
From September 1977 to December 1987, a total of 228 patients with rectal cancer at mid and lower segments received surgical treatment by stapling device in colorectostomy. All patients were followed. Two hundred and fifteen patients have survived for 1 - 10 years after operation. The 1, 3, 5, 7, 10 year survival rates were 95.8%, 69.3%, 56.3%, 46.9% and 45.7%, respectively. Surgery by stapling device with preservation of anus gives a survival comparable to those of Miles, Dixon and Bacon operation in this cancer.


Prolactin-like protein-f subfamily of placental hormones/cytokines: responsiveness to maternal hypoxia.
The prolactin (PRL) family of hormones/cytokines is involved in the maintenance of pregnancy and adaptations to physiological stressors. In this report, we identify and characterize a new member of the rat PRL family, examine the impact of maternal hypoxia on placental PRL family gene expression, and investigate maternal adaptive responses to hypoxia. Perusal of the PRL gene family locus in the rat genome resulted in the identification of a putative new member of the rat PRL family. The new member is closely related to the previously reported PRL-like protein-F (PLP-F) and has been named PLP-Fbeta and the originally characterized PLP-F, now termed PLP-Falpha. The two proteins exhibit structural similarities but possess distinct cell- and temporal-specific expression profiles. In vivo hypoxia stimulates placental PLP-Falpha and PLP-E mRNA expression in the rat and mouse, respectively. Rcho-1 trophoblast cells can differentiate into trophoblast giant cells, express PLP-Falpha, and exhibit enhanced PLP-Falpha mRNA levels when cultured under low oxygen tension (2%). Exposure to hypobaric hypoxia during latter part of pregnancy did not significantly impact the expression of PLP-Fbeta mRNA. Finally, exposure to hypobaric hypoxia during midpregnancy led to increased maternal red blood cells, hemoglobin concentrations, hematocrit, and increased concentrations of maternal splenic mRNAs for key proteins involved in hemoglobin synthesis, erythroid Krüppel-like factor, erythroid 5-aminolevulinate synthase-2, and beta-major globin. In summary, adaptive responses to maternal hypoxia include activation of placental PLP-Falpha/E gene expression, which may then participate in maternal hematological adjustments required for maintaining maternal and fetal oxygen delivery.


Effect of Lactobacteria on Bioactive Peptides and Their Sequence Identification in Mature Cheese.
An in silico study that featured the effect of starter cultures on the bioactivity and other health benefits of peptides in semi-hard cheese is presented in this contribution. Model Caciotta-type cheese samples were obtained in laboratory conditions in two variations. Sample A included starter cultures of Lactococcus lactis subsp. lactis and Lactococcus lactis subsp. cremoris. Sample B included starter cultures of Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris, and a culture of lactobacilli Lacticaseibacillus casei. The in silico method showed that the peptides inhibited angiotensin-converting enzymes (ACE) and ipeptidyl peptidase IV (DPP-4), as well as possessed antioxidant properties. Lactococcus lactis subsp. lactis and Lactococcus lactis subsp. cremoris had a greater effect on the formation of bioactive peptides.


Characterization of the phenoxyl radical in model complexes for the Cu(B) site of cytochrome c oxidase: steady-state and transient absorption measurements, UV resonance raman spectroscopy, EPR spectroscopy, and DFT calculations for M-BIAIP.
Physicochemical properties of the covalently cross-linked tyrosine-histidine-Cu(B) (Tyr-His-Cu(B)) unit, which is a minimal model complex [M(II)-BIAIPBr]Br (M = Cu(II), Zn(II)) for the Cu(B) site of cytochrome c oxidase, were investigated with steady-state and transient absorption measurements, UV resonance Raman (UVRR) spectroscopy, X-band continuous-wave electron paramagnetic resonance (EPR) spectroscopy, and DFT calculations. The pH dependency of the absorption spectra reveals that the pK(a) of the phenolic hydroxyl is ca. 10 for the Cu(II) model complex (Cu(II)-BIAIP) in the ground state, which is similar to that of p-cresol (tyrosine), contrary to expectations. The bond between Cu(II) and nitrogen of cross-linked imidazole cleaves at pH 4.9. We have successfully obtained UVRR spectra of the phenoxyl radical form of BIAIPs and have assigned bands based on the previously reported isotope shifts of Im-Ph (2-(1-imidazoyl)-4-methylphenol) (Aki, M.; Ogura, T.; Naruta, Y.; Le, T. H.; Sato, T.; Kitagawa, T. J. Phys. Chem. A 2002, 106, 3436-3444) in combination with DFT calculations. The upshifts of the phenoxyl vibrational frequencies for 8a (C-C stretching), 7a' (C-O stretching), and 19a, and the Raman-intensity enhancements of 19b, 8b, and 14 modes indicate that UVRR spectra are highly sensitive to imidazole-phenol covalent linkage. Both transient absorption measurements and EPR spectra suggest that the Tyr-His-Cu(B) unit has only a minor effect on the electronic structure of the phenoxyl radical form, although our experimental results appear to indicate that the cross-linked Tyr radical exhibits no EPR. The role of the Tyr-His-Cu(B) unit in the enzyme is discussed in terms of the obtained spectroscopic parameters of the model complex.


[Investigation and analysis of the activities of daily living of the aged at home in western China].
To investigate the current situation of the activities of daily living (ADL) of the aged at home in western China, and to analyze its influencing factors so that we can improve the quality of life and pension services of elderly people. The elderly people who came from Qinghai Province, Ningxia Autonomous Region, Xinjiang Uygur Autonomous Region, Shanxi Province, Guizhou Province, Guangxi Province, Sichuan Province, Yunnan Province and Chongqing were surveyed by questionnaires. Logistic regression model was used to analyze the influencing factors of ADL. A total of 7 175 aged people living in the western China were surveyed. In the study, 78.86% of the aged at home could independently live. 12.32% of the aged were of mild dysfunction. 6.27% of the aged had moderate dysfunction. And 2.55% of the aged suffered severe dysfunction. Multiple Logistic analyses indicated that age, educational level, economic income, body mass index and disease were the factors that affected their ADL. The risk of decreased ADL in the 60-69 and 70-79year-old groups were 0.221 (95%CI: 0.190-0.258) and 0.353 (95%CI: 0.305-0.409) times that of the elderly over the age of 80. Compared with illiterate seniors,the risks of decline in ADL of primary school, junior high school, secondary or high school, college or undergraduates, postgraduates or above were 0.299 (95%CI: 0.140-0.637), 0.312 (95%CI: 0.146-0.663), 0.238 (95%CI: 0.112-0.510), 0.226 (95%CI: 0.105-0.484), and 0.238 (95%CI: 0.110-0.514) times. The declines in the risk of ADL for elderly people with quite difficult economic conditions, slight difficulty and breaking even were 2.720 (95%CI: 2.015-3.672), 2.344 (95%CI: 1.816-3.027), and 1.542 (95%CI: 1.215-1.957) times of the economically abundant people. Compared with those with a body mass index (BMI)≥28, the risk of ADL reduction for BMI<18.5 was 1.577 (95%CI: 1.142-2.179) times. And the ADL of the elderly with no disease was at the risk of falling 0.685 (95%CI: 0.602-0.779) times that of an elderly person with the disease. The activities of daily living of age at home of western China are not high, and affected by many factors, such as age, educational level and so on. With the increasing of the elderly, maintaining and improving the ADL are the problems and challenges that we are faced with.


Vaccination with EphA2-derived T cell-epitopes promotes immunity against both EphA2-expressing and EphA2-negative tumors.
BACKGROUND: A novel tyrosine kinase receptor EphA2 is expressed at high levels in advanced and metastatic cancers. We examined whether vaccinations with synthetic mouse EphA2 (mEphA2)-derived peptides that serve as T cell epitopes could induce protective and therapeutic anti-tumor immunity. METHODS: C57BL/6 mice received subcutaneous (s.c.) vaccinations with bone marrow-derived dendritic cells (DCs) pulsed with synthetic peptides recognized by CD8+ (mEphA2671-679, mEphA2682-689) and CD4+ (mEphA230-44) T cells. Splenocytes (SPCs) were harvested from primed mice to assess the induction of cytotoxic T lymphocyte (CTL) responses against syngeneic glioma, sarcoma and melanoma cell lines. The ability of these vaccines to prevent or treat tumor (s.c. injected MCA205 sarcoma or B16 melanoma; i.v. injected B16-BL6) establishment/progression was then assessed. RESULTS: Immunization of C57BL/6 mice with mEphA2-derived peptides induced specific CTL responses in SPCs. Vaccination with mEPhA2 peptides, but not control ovalbumin (OVA) peptides, prevented the establishment or prevented the growth of EphA2+ or EphA2-negative syngeneic tumors in both s.c. and lung metastasis models. CONCLUSIONS: These data indicate that mEphA2 can serve as an attractive target against which to direct anti-tumor immunity. The ability of mEphA2 vaccines to impact EphA2-negative tumors such as the B16 melanoma may suggest that such beneficial immunity may be directed against alternative EphA2+ target cells, such as the tumor-associated vascular endothelial cells.


A human IgG1-K type M-protein with antibody activity against horse and rabbit alpha 2-macroglobulin.
A human IgG1-K type M-protein which specifically precipitates with alpha 2-macroglobulin (alpha 2-M) from horse and rabbit is described. This protein did not combine with human alpha 2-M nor with alpha 2-M from various other species. The binding activity was exclusively located in the Fab region of the molecule. This patient had never received injection of horse anti-tetanus serum. The present case seems to be the second report of an M-protein with antibody activity against horse and rabbit alpha 2-M.


Gestational growth trajectories derived from a dynamic fetal-placental scaling law.
Fetal trajectories characterizing growth rates in utero have relied primarily on goodness of fit rather than mechanistic properties exhibited in utero. Here, we use a validated fetal-placental allometric scaling law and a first principles differential equations model of placental volume growth to generate biologically meaningful fetal-placental growth curves. The growth curves form the foundation for understanding healthy versus at-risk fetal growth and for identifying the timing of key events in utero.


[Experiences with cardiac troponin assessments].
After the JESC/ACCC guideline (approved in year 2000), cardiac troponins became the first-line laboratory markers in the diagnosis of acute coronary syndrome. Since 2006, there is a hemodynamic laboratory in our Hospital and since July, 2007, there is a so called "one gate" Emergency Unit. Since the amount of the cardiac troponin assessments has risen, we aimed to analyze the background of this elevation, the results and the cause of the false positivity, as well. We analyzed our cardiac troponin results assessed in the second half of year 2008. In this time we have had 2656 cardiac troponin examination in 1787 patients. 280 positive results were examined in 203 patients, but acute coronary syndrome was proved only in 110 patients. The remaining cases were false positive but only for detecting acute coronary syndrome, because many other diseases were proved in the background of these patients, and only one result was really (literally) false positive. Because of the very low rate of positive results we have to think about restriction of asking that examination. We emphasize that there are many non-acute coronary syndrome diseases with positive cardiac troponin results. This situation needs an urgent and close communication between the clinicians and the laboratory staff.


Participation of women in clinical trials of drug therapies: a context for the controversies.
Women's participation in clinical trials, particularly those involving drugs, has been said to be both overrepresented and underrepresented. How can this be? Studies of participation are compared and contrasted to elucidate some reasons for this contradiction. The history of women's participation in clinical trials is chronicled through policies and regulations filled with restrictions. Since 1993, however, the National Institutes of Health has mandated, and the Food and Drug Administration has emphasized, inclusion of women in clinical trials, only to be thwarted by other regulations excluding many women. Gender-specific analyses are required to detect gender differences in effects of pharmaceutical and nonpharmaceutical interventions, but they are seldom performed. The exclusion of women from clinical trials means that women's healthcare is compromised by lack of sex-specific information about dosing of drugs and unique uses of drugs. A database, although currently quite limited, tracks the participation of women in clinical trials funded by federal agencies, industries, and nonprofit groups. Federal regulations have recently changed. Additional changes in access to all phases of clinical trials and enhanced monitoring of clinical trials are recommended.


Consecutive bouts of electrical stimulation-induced contractions alter ribosome biogenesis in rat skeletal muscle.
Ribosome biogenesis has been implicated in resistance exercise training (RET)-induced skeletal muscle hypertrophy. However, it is unclear how increasing bouts of RET affects ribosome content and biogenesis. This was investigated in the present study using simulated RET where rat skeletal muscle is subjected to increasing bouts of electrical stimulation. Sprague-Dawley rats were randomly assigned to the following seven groups: sedentary for 5 days (SED) or 6 wk (SED_6w), resistance-exercise trained with 1 bout (1B), 2 bouts (2B), 3 bouts (3B), 6 bouts (6B), and 18 bouts (18B). RET was simulated on the right gastrocnemius muscle by transcutaneous electric stimulation under isoflurane anesthesia, and a RET bout was given 3 times a week. Rats in 1B, 2B, and 3B groups showed increased 45S precursor (pre-) rRNA and 18S+28S rRNA content per muscle weight and elevated mRNA levels of c-myc and upstream binding factor (UBF). Increases in phosphorylated UBF and total cyclin D1 protein level were observed 48 h after RET; the former increased as a function of RET duration. In 3B, 6B, and 18B groups, the 18S+28S rRNA content per muscle weight was kept unchanged, and 45S pre-rRNA, cyclin D1, and phosphorylated UBF levels in 18B were lower than those in 3B. These results suggest that RET activates ribosome biogenesis and increases ribosome content through modulation of UBF and cyclin D1 activity at its early phase. Additional bouts of RET may not lead to a further increase in ribosome content per muscle weight through possibly the attenuation of transcription process. NEW & NOTEWORTHY Ribosome biogenesis has been implicated in resistance exercise training-induced skeletal muscle hypertrophy. However, it remains unclear how this is influenced by the volume of repeated bouts of resistance exercise training. Using resistance exercise training model with rat skeletal muscle, we provide evidence that ribosome biogenesis is stimulated by the initial few bouts of resistance exercise training with no additional effect of further increase in the exercise bout.


Purification and characterization of Candida albicans 20S proteasome: identification of four proteasomal subunits.
The 20S proteasome from yeast cells of Candida albicans was purified by successive chromatographic steps to apparent homogeneity, as judged by nondenaturing and denaturing polyacrylamide gel electrophoresis. Its molecular mass was estimated to be 640 kDa by gel filtration. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate gave at least 10 bands in the range 20-32 kDa. Two-dimensional electrophoresis revealed the presence of at least 14 polypeptides. By electron microscopy after negative staining, the proteasome preparation appeared as typical symmetrical barrel-shaped particles. The enzyme cleaved the peptidyl-arylamide bonds in the model synthetic substrates Cbz-G-G-L-p-nitroanilide, Cbz-G-G-R-beta-naphthylamide, and Cbz-L-L-E-beta-naphthylamide (chymotrypsin-like, trypsin-like, and peptidylglutamyl-peptide-hydrolyzing activities). The differential sensitivity of these activities to aldehyde peptides and sodium dodecyl sulfate supported the multicatalytic nature of this enzyme. Three proteasomal subunits were identified as alpha6/Pre5, alpha3/Y13, and alpha5/Pup2 by internal sequencing of tryptic fragments. Their sequences perfectly matched the corresponding deduced amino acid sequences of the C. albicans genes. A fourth subunit was identified as alpha7/Prs1 by immunorecognition with a monoclonal antibody specific for C8, the human proteasome subunit homologue. Treatment of the intact isolated 20S proteasome with acid phosphatase and Western blot analysis of the separated components indicated that the alpha7/Prs1 subunit is obtained as a multiply phosphorylated protein.


Assessment tool of Thai menopause-specific quality of life in Surat Thani Province, Thailand.
To develop an assessment tool of Thai menopause-specific quality of life in Surat Thani Province, Thailand. The present study divided research design into three phases. Phase I Concept clarification, a thorough study of related literature was conducted to search for the concept of menopause-specific quality of life and its existing instruments to guide developing instrument. Phase II Item development, in-depth interviews with 30 Thai menopausal women in Surat Thani was conducted and an initial pool of items relating to menopause-specific quality of life was generated to develop the instrument, then, tested with 399 menopausal women. Phase III psychometric test, the developed questionnaire was tested for validity and reliability with 402 menopausal women. The Thai Menopause-Specific Quality of Life instrument was well developed with 63 items, internal consistency reliability coefficient obtained 0.952, comprised of three domains including physic-psychological well-being (51 items), sexual-socio-economic well-being (9 items) and vasomotor well-being (3 items). The present study was directed to develop an effective instrument with integrity of psychometric property. This instrument was more meaningful to detect quality of life specific to Thai menopausal women.


Prolonged intermittent clamping of the portal triad during hepatectomy.
From 112 consecutive hepatectomies for malignant tumours performed with intermittent portal triad clamping, we have retrospectively selected the 20 cases in which clamping exceeded 90 min. Intermittent portal clamping of prolonged duration was used because of abnormal liver texture in 13 cases (mainly patients who had received intra-arterial chemotherapy) and/or because of technically difficult hepatectomy. The mean(s.d.) duration of intermittent portal clamping was 109(18) min and in two cases it exceeded 140 min (148 and 150 min). There was no postoperative mortality and the rate of postoperative morbidity was 35 per cent. Postoperative changes in biochemical liver tests were not major and transient hepatic failure occurred in only one patient following subtotal resection of the liver. We conclude that intermittent portal clamping is a useful manoeuvre in partial hepatectomy when resection is difficult or prolonged, or when the liver parenchyma is abnormal. Such clamping may be used for longer than 120 min without major complications.


Practical Considerations for the Use of Clinical Outcome Assessments (COAs) in Pediatric Clinical Research: Examples From Pediatric Gastroenterology.
Clinical outcome assessments (COAs), including patient-reported outcome (PRO) measures, are routinely used in drug development and other clinical research initiatives to assess the impact of treatment on patient health and well-being. The FDA Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims (2009), the European Medicines Agency's Reflection Paper on the Regulatory Guidance for the Use of Health-Related Quality of Life Measures in the Evaluation of Medicinal Products (2005), and the International Society for Pharmacoeconomics and Outcomes Research PRO Good Research Practices for the Assessment of Children and Adolescence Task Force (2013) outline key considerations and good measurement principles that are relevant to the selection and use of COAs in a pediatric population. However, challenges remain in the appropriate selection and use of COAs to assess treatment benefit in pediatric clinical research. The purpose of this paper is to summarize proceedings from a panel presentation at the Critical Path Institute's 2015 Annual PRO Consortium Workshop. This paper underscores the importance of considering children's specific needs and the numerous challenges faced when developing and implementing well-defined and reliable COAs in pediatric clinical trials evaluating medical products, and describes some approaches to addressing these unique needs and challenges.


Melanin as a virulence factor in pathogenic fungi.
The pigment melanin is found universally in nature and is attributed to a variety of functions. In some fungi it is thought to play a decisive role in the determination of virulence. This review examines the experimental evidence which has led to an understanding of the mechanisms by which melanin functions in pathogenic fungi, particularly in plant pathogens, in Cryptococcus neoformans and Wangiella dermatitidis.


A peptidase activity from primate liver that inactivates oxytocin in vitro: purification and partial characterization.
An aminopeptidase from monkey (Macaca radiata) liver, inactivating oxytocin in vitro and located predominantly in the lysosomal and microsomal fractions, was purified by chromatography on Bio-Gel HTP, DEAE-Sephacel and nickel ion chelate gel and gel filtration on Sephacryl S300. Absence of binding to nickel ion chelate gel indicated the absence of exposed histidine and thiol residues on the enzyme. The enzyme appeared to be a high molecular weight (Mr 106,000) monomeric protein. It was sensitive to inhibition by metal chelators and was found to be a zinc metalloprotein by atomic absorption spectrophotometry. Divalent metal ions Ni2+ and Co2+, and sulphydryl activators glutathione and 2-mercaptoethanol had activating effects, while 4-chloro mercuribenzoate, amino acids with large hydrophobic side chains and L-cystine, beta-lactam antibiotic cloxacillin and peptidase inhibitor amastatin had inhibitory effects on the enzyme activity. The enzyme was most active against S-benzyl L-cysteine 4-nitroanilide substrate. The properties of the enzyme were distinct from those of the well-characterized alanine and leucine aminopeptidases (EC 18.104.22.168 and EC 22.214.171.124 respectively) of liver, and of primate placental cystine aminopeptidases (EC 220.127.116.11).


The ethics of recruiting foreign nurses.
Because they face a growing nursing shortage, many U.S. health care institutions have turned to recruiting foreign nurses. For foreign nurses, the practice is often an opportunity to make a better life for themselves and their families. And it helps solve a serious problem for the U.S. organizations involved. But the recruitment of foreign nurses raises a number of ethical questions. The first article here examines the practice as seen from three viewpoints, the global, that of the particular recruiting health care organization, and that of the recruited foreign nurse. The author concludes that the practice can be both a "blessing" and a "curse." The second article discusses the practice as seen from a Third World nation from which the United States, along with other Western countries, is recruiting nurses. The author, who formerly supported the practice, now opposes it.


Effects of ether and pentobarbital anesthesia on thyroid function in the rat.
Studies were performed to examine the effect of two anesthetic agents, ether and pentobarbital, on the hypothalamic-pituitary-thyroid function in vivo. In non-anesthetized animals, plasma thyrotropin (TSH) increased rapidly from basal values of 0.1, a peak of 0.49 microng/ml, 25 min after exposure to the cold. Anesthesia with ether during exposure to the cold completely prevented the rise in TSH. During pentobarbital anesthesia, the rise in TSH after exposure to cold was reduced by more than 90%. Even a three minute period of ether anesthesia prior to cold exposure reduced the peak response to cold as well as delayed this response when compared to the untreated group. During two hours of anesthesia with ether, the TSH concentration declined in animals which were fed a low iodine diet at essentially the same rate as in animals on the same diet given an injection of 3 microng of triiodothyronine. Pentobarbital did not suppress TSH at room temperature. The release of thyrotropin after injection of synthetic thyrotropin-releasing hormone (TRH) was greater in animals anesthetized with pentobarbital than in controls and was slightly reduced in ether-anesthetized animals. This difference was observed when thyrotropin was given intraperitoneally or intravenously and the slope of the dose-response curves to TRH showed a flattening of the curve of rats treated with ether and a steeper slope of response in animals anesthetized with pentobarbital. We conclude that pentobarbital inhibited TSH response to cold but did not reduce the resting levels. Ether inhibited the rise of TSH in the cold and lowered the basal levels of TSH in animlas at room temperature. Pentobarbital increased the response to TRH and ether may have reduced the response to TRH.


Genetic variation in APOL1 and MYH9 genes is associated with chronic kidney disease among Nigerians.
A region of chromosome 22 which includes APOL1 and MYH9 genes was recently identified as a risk locus for non-diabetic forms of kidney disease, including idiopathic and HIV-associated focal segmental glomerular sclerosis and kidney disease clinically attributed to hypertension among African Americans. The purposes of the current study were, therefore, to examine the frequency of these variants and to determine whether they are associated with chronic kidney disease (CKD) among native Africans. To investigate the possible evidence of association between variants in these genes and non-diabetic CKD among West Africans, we performed a case/control analysis in a sample of 166 Nigerians without history of European admixture. Our study included a total of 9 variants on APOL1 (n = 4) and MYH9 (n = 5) genes. We observed significantly strong associations with previously reported APOL1 variants rs73885319 and rs60910145, and their two-allele "G1" haplotype (P < 0.005). We did not observe significant evidence of association between non-diabetic CKD and any of the MYH9 variants or haplotypes after accounting for multiple testing in our sample. In conclusion, APOL1 risk variants are associated with non-diabetic forms of CKD among Nigerians of Yoruba ethnicity. Further information on APOL1/MYH9 variants may lead to screening programs, which could lead to earlier detection and interventions for non-diabetic kidney disease.


THz Sensing of Human Skin: A Review of Skin Modeling Approaches.
The non-ionizing and non-invasive nature of THz radiation, combined with its high sensitivity to water, has made THz imaging and spectroscopy highly attractive for in vivo biomedical applications for many years. Among them, the skin is primarily investigated due to the short penetration depth of THz waves caused by the high attenuation by water in biological samples. However, a complete model of skin describing the THz-skin interaction is still needed. This is also fundamental to reveal the optical properties of the skin from the measured THz spectrum. It is crucial that the correct model is used, not just to ensure compatibility between different works, but more importantly to ensure the reliability of the data and conclusions. Therefore, in this review, we summarize the models applied to skin used in the THz regime, and we compare their adaptability, accuracy, and limitations. We show that most of the models attempt to extract the hydration profile inside the skin while there is also the anisotropic model that displays skin structural changes in the stratum corneum.


A systematic review of school drug education.
This paper provides an up-to-date systematic review of the school drug education literature (to June 2001) and identifies components that have the potential for creating effective drug education programmes in schools. This paper is a summary of a 150-page review. The review adopts a well-defined search methodology, specific selection criteria, and has made a series of recommendations based on the findings of past reviews and recent primary studies that met the selection criteria. The review is inclusive of reviews and recent primary studies that involved young people in school settings that encompassed a classroom intervention, included drug-related behavioural measures and had a positive impact on students' drug-related behaviours. The review identifies several areas that should be the focus of future programmes. These include timing and programming issues, content and delivery issues, teacher training, and dissemination. There is much refinement that can occur in school drug education implementation and research. The way forward is to continue to create and test interventions that bring together all components of the development, implementation and evaluation of school drug education that are effective in creating behaviour change, and that are practical to the school setting.


Linguistic Multi-Attribute Group Decision Making with Risk Preferences and Its Use in Low-Carbon Tourism Destination Selection.
Low-carbon tourism plays an important role in carbon emission reduction and environmental protection. Low-carbon tourism destination selection often involves multiple conflicting and incommensurate attributes or criteria and can be modelled as a multi-attribute decision-making problem. This paper develops a framework to solve multi-attribute group decision-making problems, where attribute evaluation values are provided as linguistic terms and the attribute weight information is incomplete. In order to obtain a group risk preference captured by a linguistic term set with triangular fuzzy semantic information, a nonlinear programming model is established on the basis of individual risk preferences. We first convert individual linguistic-term-based decision matrices to their respective triangular fuzzy decision matrices, which are then aggregated into a group triangular fuzzy decision matrix. Based on this group decision matrix and the incomplete attribute weight information, a linear program is developed to find an optimal attribute weight vector. A detailed procedure is devised for tackling linguistic multi-attribute group decision making problems. A low-carbon tourism destination selection case study is offered to illustrate how to use the developed group decision-making model in practice.


The Roles of Aquaporins in Plant Stress Responses.
Aquaporins are membrane channel proteins ubiquitously present in all kingdoms of life. Although aquaporins were originally discovered as water channels, their roles in the transport of small neutral solutes, gasses, and metal ions are now well established. Plants contain the largest number and greatest diversity of aquaporin homologs with diverse subcellular localization patterns, gating properties, and solute specificity. The roles of aquaporins in physiological functions throughout plant growth and development are well known. As an integral regulator of plant-water relations, they are presumed to play an important role in plant defense responses against biotic and abiotic stressors. This review highlights involvement of various aquaporin homologs in plant stress responses against a variety of environmental stresses that disturb plant cell osmotic balance and nutrient homeostasis.


The AAA+ proteins Pontin and Reptin enter adult age: from understanding their basic biology to the identification of selective inhibitors.
Pontin and Reptin are related partner proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They are implicated in multiple and seemingly unrelated processes encompassing the regulation of gene transcription, the remodeling of chromatin, DNA damage sensing and repair, and the assembly of protein and ribonucleoprotein complexes, among others. The 2nd International Workshop on Pontin and Reptin took place at the Instituto de Tecnologia Química e Biológica António Xavier in Oeiras, Portugal on October 10-12, 2014, and reported significant new advances on the mechanisms of action of these two AAA+ ATPases. The major points under discussion were related to the mechanisms through which these proteins regulate gene transcription, their roles as co-chaperones, and their involvement in pathophysiology, especially in cancer and ciliary biology and disease. Finally, they may become anticancer drug targets since small chemical inhibitors were shown to produce anti-tumor effects in animal models.


Lipid-Based Nanoparticle Formulation of Diallyl Trisulfide Chemosensitizes the Growth Inhibitory Activity of Doxorubicin in Colorectal Cancer Model: A Novel In Vitro, In Vivo and In Silico Analysis.
Garlic's main bioactive organosulfur component, diallyl trisulfide (DATS), has been widely investigated in cancer models. However, DATS is not suitable for clinical use due to its low solubility. The current study seeks to improve DATS bioavailability and assess its chemopreventive and chemosensitizing properties in an AOM-induced colorectal cancer model. The polyethylene glycol coated Distearoylphosphatidylcholine/Cholesterol (DSPC/Chol) comprising DATS-loaded DATSL and doxorubicin (DOXO)-encapsulated DOXL liposomes was prepared and characterized. The changes in the sensitivity of DATS and DOXO by DATSL and DOXL were evaluated in RKO and HT-29 colon cancer cells. The synergistic effect of DATSL and DOXL was studied by cell proliferation assay in the combinations of IC10, IC25, and IC35 of DATSL with the IC10 of DOXL. AOM, DATSL, and DOXL were administered to different groups of mice for a period of 21 weeks. The data exhibited ~93% and ~46% entrapment efficiency of DATSL and DOXL, respectively. The size of sham liposomes was 110.5 nm, whereas DATSL and DOXL were 135.5 nm and 169 nm, respectively. DATSL and DOXL exhibited significant sensitivity in the cell proliferation experiment, lowering their IC50 doses by more than 8- and 14-fold, respectively. However, the DATSL IC10, IC25, and IC35 showed escalating chemosensitivity, and treated the cells in combination with DOXL IC10. Analysis of histopathological, cancer marker enzymes, and antioxidant enzymes revealed that the high dose of DATSL pretreatment and DOXL chemotherapy is highly effective in inhibiting AOM-induced colon cancer promotion. The combination of DATSL and DOXL indicated promise as a colorectal cancer treatment in this study. Intermolecular interactions of DATS and DOXO against numerous cancer targets by molecular docking indicated MMP-9 as the most favourable target for DATS exhibiting binding energy of -4.6 kcal/mol. So far, this is the first research to demonstrate the chemopreventive as well as chemosensitizing potential of DATSL in an animal model of colorectal cancer.


Involvement of the Sst1 somatostatin receptor subtype in the intrahypothalamic neuronal network regulating growth hormone secretion: an in vitro and in vivo antisense study.
Five somatostatin (SRIH) receptors (sst1-5) have been cloned. Recent anatomical evidence suggests that sst1 and sst2 may be involved in the central regulation of GH secretion. Given the lack of specific receptor antagonists, we used selective antisense oligodeoxynucleotides (ODNs) to test the hypothesis that one or both of these subtypes are involved in the intrahypothalamic network regulating pulsatile GH secretion. In mouse neuronal hypothalamic cultures the proportion of GHRH neurons coexpressing sst1 or sst2 messenger RNAs (mRNAs) was identical. In contrast, sst1 mRNAs were more often present than sst2 in SRIH-expressing neurons. Firstly, sst1 antisense ODN in vitro treatment abolished sst1, but not sst2, receptor modulation of glutamate sensitivity and decreased sst1, but not sst2, mRNAs. The reverse was true after treatment with sst2 antisense. Sense ODNs did not alter the effects of SRIH agonists. In a second series of experiments, nonanaesthetized adult male rats were infused for 120 h intracerebroventricularly with ODNs. Only the sst1 antisense ODN diminished the amplitude of ultradian GH pulses without modifying their frequency. In parallel, sst1 antisense ODN strongly diminished sst1 immunoreactivity in the anterior periventricular nucleus and median eminence, as well as sstl periventricular nucleus mRNA levels. The effectiveness of the sst2 antisense ODN was attested by the inhibition of hypothalamic binding of [125I]Tyr0-D-Trp8-SRIH. Scrambled ODNs had no effect on GH secretion or on sst mRNAs or SRIH binding levels. These results favor a preferential involvement of sst1 receptors in the intrahypothalamic regulation of GH secretion by SRIH.


Systemic thinking: how do we know it when we see it?
One discussion within the field of family-oriented care concerns the distinction between those who practise a family approach and those who think in family system terms. This paper presents a comprehensive model of systemic thinking that may be useful for both family systems teachers and researchers. The conceptual model includes: (i) clinicians' experiences with and attitudes towards family aspects of health problems, and the context of clinicians' judgements about these problems; (ii) the way clinicians organize their knowledge about family factors and health problems in order for that knowledge to be readily available for decision making; and (iii) the interview sequences and hypothesis-generating or testing strategies used by clinicians in encounters with patients. The extent to which clinicians exhibit systemic thinking can be determined through interviews, questionnaires and case materials such as encounter transcripts. A method that assesses systemic thinking allows rigorous evaluations of family-oriented teaching efforts and clinical interventions.


Analgesic addiction and pseudoaddiction in painful chronic illness.
Research is needed to enable more effective assessment and treatment of analgesic addiction among patients with painful chronic illnesses and to improve our understanding of the staff-patient interactions that give rise to pseudoaddiction. This study tested predictions that certain drug-use behaviors and pain-coping strategies were associated with analgesic addiction, and that certain were associated with risk of pseudoaddiction. Analgesic addiction and risk of pseudoaddiction among patients with sickle cell disease were measured by symptom counts, using an interview method for classifying symptoms as pain-related (pseudoaddiction) or non-pain-related (analgesic addiction). Concern-raising drug-use behaviors and treatment requirements for pain were also assessed, and participants completed the pain-coping strategies questionnaire. Qualitative case descriptions of patients meeting criteria for analgesic addiction and pseudoaddiction were examined to identify common and distinctive features of the two groups. Consistent with predictions, multiple regression analyses showed that disputes about analgesics were independently associated with risk of pseudoaddiction. Physiological dependence and illicit drug use were both associated with analgesic addiction, independently of other factors. The qualitative data showed that analgesic addiction was not an obvious, clear-cut phenomenon: addiction and pseudoaddiction were superficially similar, and even symptoms of genuine addiction originated in patients' experiences of pain and illness. These tentative findings were broadly consistent with what is known about analgesic addiction and pseudoaddiction in other painful conditions. They also suggested that current recommendations about addiction in pain patients could understate the potential importance of physiological dependence. The findings could inform staff training programs to improve pain management and reduce the incidence of pseudoaddiction. The classification of pain-related and non-pain-related symptoms could be used in further research on the development of analgesic addiction and the factors that influence staff attributions about addiction in patients with pain.


Understanding glycine conformation through molecular orbitals.
The four most stable C(s) conformers of glycine have been investigated using a variety of quantum-mechanical methods based on Hartree-Fock theory, density-functional theory (B3LYP and statistical average of orbital potential), and electron propagation (OVGF) treatments. Information obtained from these models were analyzed in coordinate and momentum spaces using dual space analysis to provide insight based on orbitals into the bonding mechanisms of glycine conformers, which are generated by rotation of C-O(H) (II), C-C (III), and C-N (IV) bonds from the global minimum structure (I). Wave functions generated from the B3LYP/TZVP model revealed that each rotation produced a unique set of fingerprint orbitals that correspond to a specific group of outer valence orbitals, generally of a' symmetry. Orbitals 14a', 13a', 12a', and 11a' are identified as the fingerprint orbitals for the C-O(H) (II) rotation, whereas fingerprint orbitals for the C-C (III) bond rotation are located as 16a' [highest occupied molecular orbital (HOMO)], 15a' [next highest molecular occupied molecular orbital (NHOMO)], 14a', and 12a' orbitals. Fingerprint orbitals for IV generated by the combined rotations around the C-C, C-O(H), and C-N bonds are found as 16a', 15a', 14a', 13a', and 11a', as well as in orbitals 2a" and 1a". Orbital 14a' is identified as the fingerprint orbital for all three conformational processes, as it is the only orbital in the outer valence region which is significantly affected by the conformational processes regardless rotation of which bond. Binding energies, molecular geometries, and other molecular properties such as dipole moments calculated based on the specified treatments agree well with available experimental measurements and with previous theoretical calculation.


The worries adult children and their parents experience for one another.
This study examined the worries adults and their parents experience for one another. To date, relatively little research has considered the experience of worry in this relationship. A small number of studies, however, suggest worry is relatively common in this relationship (Boutain, 2001; Cicirelli, 1988; Parker, Call, Dunkle, & Vaitkus, 2002). Furthermore, worrying may be linked with mental and physical health (Beck et al., 2001; Hoyer, Becker, & Roth, 2001). A son or daughter (aged 22 to 49) and mother and father (aged 40 to 84) from 213 families participated. Adult children worried primarily about their parents' health. Interestingly, adult children with older parents were not more likely than adult children with younger parents to worry about their parents' health. In contrast, parents' worries were more diverse than those of adult children and included worries about their adult children's health, safety, relationships, and finances, among others. Furthermore, parents' worries were associated with their perceptions of relationship quality. Notably, parents who worried about their adult children's finances reported having poorer quality relationships with their adult children than parents who experienced other worries (e.g., about safety).


Testing the applicability of Nernst-Planck theory in ion channels: comparisons with Brownian dynamics simulations.
The macroscopic Nernst-Planck (NP) theory has often been used for predicting ion channel currents in recent years, but the validity of this theory at the microscopic scale has not been tested. In this study we systematically tested the ability of the NP theory to accurately predict channel currents by combining and comparing the results with those of Brownian dynamics (BD) simulations. To thoroughly test the theory in a range of situations, calculations were made in a series of simplified cylindrical channels with radii ranging from 3 to 15 Å, in a more complex 'catenary' channel, and in a realistic model of the mechanosensitive channel MscS. The extensive tests indicate that the NP equation is applicable in narrow ion channels provided that accurate concentrations and potentials can be input as the currents obtained from the combination of BD and NP match well with those obtained directly from BD simulations, although some discrepancies are seen when the ion concentrations are not radially uniform. This finding opens a door to utilising the results of microscopic simulations in continuum theory, something that is likely to be useful in the investigation of a range of biophysical and nano-scale applications and should stimulate further studies in this direction.


CNV Workshop: an integrated platform for high-throughput copy number variation discovery and clinical diagnostics.
Recent studies have shown that copy number variations (CNVs) are frequent in higher eukaryotes and associated with a substantial portion of inherited and acquired risk for various human diseases. The increasing availability of high-resolution genome surveillance platforms provides opportunity for rapidly assessing research and clinical samples for CNV content, as well as for determining the potential pathogenicity of identified variants. However, few informatics tools for accurate and efficient CNV detection and assessment currently exist. We developed a suite of software tools and resources (CNV Workshop) for automated, genome-wide CNV detection from a variety of SNP array platforms. CNV Workshop includes three major components: detection, annotation, and presentation of structural variants from genome array data. CNV detection utilizes a robust and genotype-specific extension of the Circular Binary Segmentation algorithm, and the use of additional detection algorithms is supported. Predicted CNVs are captured in a MySQL database that supports cohort-based projects and incorporates a secure user authentication layer and user/admin roles. To assist with determination of pathogenicity, detected CNVs are also annotated automatically for gene content, known disease loci, and gene-based literature references. Results are easily queried, sorted, filtered, and visualized via a web-based presentation layer that includes a GBrowse-based graphical representation of CNV content and relevant public data, integration with the UCSC Genome Browser, and tabular displays of genomic attributes for each CNV. To our knowledge, CNV Workshop represents the first cohesive and convenient platform for detection, annotation, and assessment of the biological and clinical significance of structural variants. CNV Workshop has been successfully utilized for assessment of genomic variation in healthy individuals and disease cohorts and is an ideal platform for coordinating multiple associated projects. Available on the web at: http://sourceforge.net/projects/cnv.


Kurashiki Prehospital Stroke Subtyping Score (KP3S) as a means of distinguishing ischemic from hemorrhagic stroke in emergency medical services.
The aim of this study was to devise a new ischemic stroke (IS)/hemorrhagic stroke (HS) stroke score to distinguish IS from HS for emergency medical services (EMS). We studied patients with IS and HS who were admitted within 6 h of onset and transferred by the EMS. We compared characteristics of IS and HS to devise a new IS/HS score. A total of 227 patients (median age, 71 years; 139 males; IS, 127 patients; HS, 100 patients) were included in the study. On multivariate analysis following univariate analysis, presence of atrial fibrillation, diastolic blood pressure <100 mm Hg and lack of disturbance of consciousness were independently associated with IS. The following score was devised to distinguish IS from HS in EMS: Kurashiki Prehospital Stroke Subtyping Score (KP3S) = (presence of atrial fibrillation) · 2 + (diastolic blood pressure <100 mm Hg) + (lack of disturbance of consciousness). When KP3S was greater than 1, sensitivity for IS was 64% and specificity 85%. The C statistic of KP3S was 0.805. KP3S is useful for distinguishing IS from HS and for the evaluation of stroke patients by EMS.


[Study of the separation factors of basic compounds in HPLC using a reversed-phase amino-type column].
The chromatographic behaviors of some basic probes and a neutral reference compound were investigated as functions of temperature, buffer cation strength and flow-rate using a novel reversed-phase amino-type column at both pH 3.0 and pH 7.0. The results showed that the retention of basic compounds declined steeply at first, but then slowly when temperature increased continually at pH 3.0 while decreased slowly in the whole range of temperature at pH 7.0. The column efficiency increased and the peak shape improved with increased temperature. The buffer cation strength has a strong effect on the retention of bases. The optimum flow-rate for the highest efficiency is generally lower for basic compounds than neutral compounds, and due to the steepness of the van Deemter curves obtained, high flow-rates appear to be particularly detrimental in the chromatography of basic compounds. All the results indicated that the retention mechanism, was more complex for the analysis of bases on amino-type columns than on traditional reversed-phase columns because of the existence of amino group in the alkyl group of amino-type columns.