Mixed-methods approach to understanding nurses' clinical reasoning in recognizing delirium in hospitalized older adults.
A mixed-methods study was conducted to enhance understanding of nurses' clinical reasoning in recognizing delirium in the hospitalized older adult. Paired nurse and researcher ratings of the confusion assessment method in 103 medical-surgical patients were analyzed to determine the rate of agreement in detecting delirium and to identify a purposive sample of nurses to be interviewed about the patients with delirium who were under their care. Nurses' clinical reasoning in recognizing and underrecognizing delirium was investigated using semistructured interviews. The incidence of delirium was 13%, with poor agreement (95% CI [0.05, 0.64], p < 0.05) between the researchers and the nurses in detecting delirium. Sixteen nurses were interviewed and transcripts were analyzed with grounded theory. Confusion was the primary causal factor for recognizing symptoms of delirium. The findings explicated a framework that forms the basis for generating testable assumptions to improve nurses' recognition of delirium.


Towards understanding the impact of plastics on freshwater and marine microalgae: A review of the mechanisms and toxicity endpoints.
Plastics are ubiquitous and persistent in aquatic environments, threatening environmental and human health. This review focused on the effects of plastics (single toxicity) and associated chemicals (combined or leachate toxicities) on freshwater and marine microalgae. Forty-seven publications from 2010 to 2020 were used in this review. Based on their topic of focus, we classified the publications among the following categories: single plastic toxicity, combined toxicity of plastics and other chemicals, and toxicity of leachates released from plastics. The test species Chlorophyta and Ochrophyta were generally used to assess the impacts of plastics on aquatic microalgae. This study identified the inhibition of algal growth and photosynthesis due to single toxicity through the physical adsorption of plastics, showing that leachates released from plastics contained non-specific chemicals which could potentially affect microalgae. Production of malondialdehyde or reactive oxygen species presented significant effects on algae independent of the experimental conditions. This review could improve our understanding of the effects of plastic pollution on microalgae in freshwater and marine environments. It has implications for further research in this field and associated water management in light of the global ubiquity of plastic pollution.


Pneumococcal disease manifestation in children before and after vaccination: what's new?
Pneumococcal infections remain a relevant cause of morbidity and mortality in children, especially in countries where vaccination has not been introduced. In contrast to the common belief by many pediatricians, the most important pneumococcal infections are of the respiratory tract and not invasive diseases. The recent pandemic of the H1N1 virus prompted studies to better understand the interaction between the influenza virus, Streptococcus pneumoniae, and pneumonia outcomes. Radiological findings of bacteremic pneumonia have been well investigated and besides the typical alveolar consolidation, a broad spectrum of atypical patterns has been reported. Molecular techniques, such as real-time polymerase chain reaction (PCR), can improve the detection of S. pneumoniae in sterile fluids, mainly in regions where previous antibiotic therapy is a common practice. In the post vaccination era, new manifestations of pneumococcal invasive disease, such as hemolytic uremic syndrome, have increased in association with parapneumonic empyema. Moreover, serotypes not included in PCV7, particularly serotypes 1, 3, 5, 7F, and 19A, have been among the most common isolates in pneumococcal disease. In Latin America, pneumococcal primary peritonitis has been described as an important clinical syndrome in a growing proportion of patients, mainly in girls. The development of newer and more specific diagnostic markers to distinguish bacterial and viral pneumonia are urgently sought, and will be especially pertinent after the introduction of pneumococcal conjugate vaccines with expanded serotypes. Such markers would minimize inappropriate diagnosis of false positive cases and treatment with antibacterial agents, while increasing positive predictive values for diagnosis of bacterial pneumonia. The extension of serotype coverage with the new conjugate vaccines is promising for pneumococcal infections and coverage against antibiotic-resistant strains.


Effects of lettuce glycoside B in ameliorating pulmonary fibrosis induced by irradiation exposure and its anti-oxidative stress mechanism.
The present research assessed the effects of lettuce glycoside B (LGB), a compound separated and purified from Pterocypsela laciniata, on irradiation-induced pulmonary fibrosis and explored the mechanism involved. Animal model of irradiation exposure inducing pulmonary fibrosis was established by Co irradiator. Rats were intraperitoneally treated with LGB (100, 200 and 400 mg/kg) once per day for a month. Lung index data were analyzed. The levels of fibrosis were assessed by hydroxyproline (Hyp) of pulmonary and lung tissue sections after irradiation exposure. Alveolitis and fibrosis levels were calculated from semi-quantitative analysis of hematoxylin and eosin and Masson's trichrome lung section staining. The serum levels of transforming growth factor β1 (TGF-β1), interleukin (IL)-6, and tumor necrosis factor-α (TNF-α) were also evaluated. Antioxidant enzymes of superoxide dismutase (SOD) were measured in serum. Moreover, we also measured serum malondialdehyde (MDA) levels, a marker of oxidative stress. Treatment with LGB significantly reduced mortality rates and lung index scores and MDA content, enhanced SOD and other antioxidant enzymes activity, and regulated serum levels of TGF-β1, IL-6, and TNF-α. These results demonstrated that LGB significantly inhibited irradiation-induced pulmonary fibrosis. Furthermore, the results suggested promising clinical effect of LGB therapies for treating irradiation-induced pulmonary fibrosis.


[Angiotensin converting enzyme and left ventricular hypertrophy in uremic patients: correlation and therapeutic options].
Anemia has been shown to be a key component of renal failure, as well as of the occurrence of left ventricular hypertrophy (LVH), with special attention paid to the paracrine mechanism of left ventricular remodelling. The aim of the study was to analyze possible association of serum angiotensin-converting enzyme (ACE) activity and LVH in hemodialysis patients with anemia treated with human recombinant erythropoietin (rHuEpo) during six months. LV geometry was determined by echocardiographic analysis in 20 hemodialysis patients before and after erythropoietin treatment. Serum ACE activity was measured by spectrophotometric method using hippyril-l-histidyl-l-leucin as a substrate. Serum ACE activity increased to 47.3% in hemodialysis patients with LVH as compared to patients with normal LV mass. A significant positive correlation was found between the level of ACE activity and LV mass index (p=0.004). Six-month erythropoietin treatment of anemia led to a significant reduction of LV mass index (p<0.008) and serum ACE activity (p=0.003) from the initial values. The levels of serum ACE activity are associated with LV geometry. Our findings suggested the possibility of simultaneous and modest modulation of LV mass and serum ACE activity with rHuEpo correction of renal anemia.


Cross-reactivity of herpesvirus-specific CD8 T cell lines toward allogeneic class I MHC molecules.
Although association between persistent viral infection and allograft rejection is well characterized, few examples of T-cell cross-reactivity between self-MHC/viral and allogeneic HLA molecules have been documented so far. We appraised in this study the alloreactivity of CD8 T cell lines specific for immunodominant epitopes from human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV). CD8 T cell lines were generated after sorting with immunomagnetic beads coated with either pp65(495-503)/A*0201, BMLF1(259-267)/A*0201, or BZLF1(54-64)/B*3501 multimeric complexes. Alloreactivity of the CD8 T cell lines against allogeneic class I MHC alleles was assessed by screening of (i) TNF-alpha production against COS-7 cells transfected with as many as 39 individual HLA class I-encoding cDNA, and (ii) cytotoxicity activity toward a large panel of HLA-typed EBV-transformed B lymphoblastoid cell lines. We identified several cross-reactive pp65/A*0201-specific T cell lines toward allogeneic HLA-A*3001, A*3101, or A*3201. Moreover, we described here cross-recognition of HLA-Cw*0602 by BZLF1/B*3501-specific T cells. It is noteworthy that these alloreactive CD8 T cell lines showed efficient recognition of endothelial cells expressing the relevant HLA class I allele, with high level TNF-alpha production and cytotoxicity activity. Taken together, our data support the notion that herpes virus-specific T cells recognizing allo-HLA alleles may promote solid organ rejection.


[Change in plasma microparticle procoagulant activity after traumatic brain injury].
To observe the serial changes of plasma microparticle procoagulant activity in patients with traumatic brain injury (TBI) and evaluate its correlations with outcome and pathophysiology of TBI. A total of 139 consecutive patients with isolated moderate or severe head trauma and 40 age- and sex-matched healthy controls were enrolled. Plasma samples were obtained on entry in healthy controls, as well as on admission and at day 1, day 2, day 3, day 5, and day 7 after TBI in the patients. Its concentration was measured by a prothrombinase assay. Fifty patients (36.0%) died from TBI in a month. After TBI, plasma microparticle procoagulant activity in the patients increased during the 6-hour period immediately, peaked in 24 hours and decreased gradually thereafter. It was substantially higher than that of healthy controls during the 7-day period using analysis of covariate (P < 0.01). A multivariate analysis selected plasma microparticle procoagulant activity (OR 1.432, 95% CI 1.194-1.719, P < 0. 01) as an independent predictor for 1-month mortality. Plasma microparticle procoagulant activities of non-survivals were statistically significantly higher than those of survivals (P = 0.01), and plasma microparticle procoagulant activities of patients with severe TBI were obviously higher than those of patients with moderate TBI (P = 0.002) using repeated-measures analysis. Plasma microparticle procoagulant activities of patients were negatively associated with Glasgow coma scale scores using Spearman correlation coefficient (P < 0.05). A multivariate linear regression selected plasma D-dimer level (P = 0.012) and plasma C-creative protein level (P = 0.019) related to plasma microparticle procoagulant activities. A receiver operating characteristic curve identified the cutoff levels of plasma microparticle procoagulant activities (12.2 U/ml) predicting 1-month mortality of patients with the high sensitivity (72.0%) and specificity values (85.4%). Areas under curve (AUC) of plasma resistin level (AUC = 0.847 +/- 0.037) was smaller than those of GCS scores (AUC = 0.917 +/- 0.023), but this difference failed to reach statistical significance (P = 0.104). Increased activity of plasma microparticle procoagulant is found after traumatic brain injury. It may contribute to inflammatory reaction and coagulation cascade and is associated with a poor clinical outcome.


The diagnosis of loosening in total hip prostheses. Clinical, radiographic and scintigraphic investigation.
Based on the authors' clinical experience and a review of the literature, the methods used for the diagnosis of loosening in hip arthroprostheses are considered. Clinical and radiographic monitoring are essential but the authors believe that in suspected loosening it is particularly important to perform bone scintigraphy using Tc 99 M.D.P., Ga 67, and Indium 111. Arthrography is advised only in selected cases. The criteria of evaluation in the various tests are reported and a procedure for diagnosis is proposed.


Transcranial bright light treatment via the ear canals in seasonal affective disorder: a randomized, double-blind dose-response study.
Bright light treatment is effective for seasonal affective disorder (SAD), although the mechanisms of action are still unknown. We investigated whether transcranial bright light via the ear canals has an antidepressant effect in the treatment of SAD. During the four-week study period, 89 patients (67 females; 22 males, aged 22-65, mean ± SD age: 43.2 ± 10.9 years) suffering from SAD were randomized to receive a 12-min daily dose of photic energy of one of three intensities (1 lumen/0.72 mW/cm(2); 4 lumens/2.881 mW/cm(2); 9 lumens/6.482 mW/cm(2)) via the ear canals. The light was produced using light-emitting diodes. The severity of depressive symptoms was assessed with the Hamilton Depression Rating Scale - Seasonal Affective Disorder (SIGH-SAD), the Hamilton Anxiety Rating Scale (HAMA), and the Beck Depression Inventory (BDI). Cognitive performance was measured by the Trail Making Test (TMT). The within-group and between-group changes in these variables throughout the study were analysed with a repeated measures analysis of variance (ANOVA), whereas gender differences at baseline within the light groups were analysed using Student's t-tests. Patients in all three groups showed significant decreases in their BDI, HAMA, and SIGH-SAD scores. Response rates, i.e., an at least 50% decrease of symptoms as measured by the BDI, were 74%-79% in the three treatment groups. Corresponding variations for the SIGH-SAD and the HAMA were 35-45% and 47-62%, respectively. No intensity-based dose-response relationships in the improvement of anxiety and depressive symptoms or cognitive performance between treatment groups were observed. Approximately one in four patients experienced mild adverse effects, of which the most common were headache, insomnia, and nausea. These results suggests that transcranial bright light treatment may have antidepressant and anxiolytic effect in SAD patients, as both self- and psychiatrist-rated depressive and anxiety symptoms decreased in all treatment groups. These improvements are comparable to findings of earlier bright light studies that used conventional devices. The lack of dose response may be due to a saturation effect above a certain light intensity threshold. Further studies on the effects of transcranial bright light with an adequate placebo condition are needed. NCT01293409, ClinicalTrials.gov.


Predictors of Intent to Leave the Job Among Home Health Workers: Analysis of the National Home Health Aide Survey.
To identify agency policies and workplace characteristics that are associated with intent to leave the job among home health workers employed by certified agencies. Data are from the 2007 National Home and Hospice Care Survey/National Home Health Aide Survey, a nationally representative, linked data set of home health and hospice agencies and their workers. Logistic regression with survey weights was conducted to identify agency and workplace factors associated with intent to leave the job, controlling for worker, agency, and labor market characteristics. Job satisfaction, consistent patient assignment, and provision of health insurance were associated with lower intent to leave the job. By contrast, being assigned insufficient work hours and on-the-job injuries were associated with greater intent to leave the job after controlling for fixed worker, agency, and labor market characteristics. African American workers and workers with a higher household income also expressed greater intent to leave the job. This is the first analysis to use a weighted, nationally representative sample of home health workers linked with agency-level data. The findings suggest that intention to leave the job may be reduced through policies that prevent injuries, improve consistency of client assignment, improve experiences among African American workers, and offer sufficient hours to workers who want them.


Disparities in neonatal abstinence syndrome and health insurance status: A statewide study using non-claims real-time surveillance data.
Most studies examining the relationship between neonatal abstinence syndrome (NAS) and health insurance status in the United States (USA) have used administrative insurance claims data, which is subject to myriad limitations. We examined the association between NAS and health insurance status in a large geographically defined rural population in the United States, using non-claims data. We utilized data from a population-based cohort of all newborns born in 2017-2019 in the rural state of West Virginia (WV) and restricted analyses to WV residents' births (n = 46 213). NAS was defined as neonatal withdrawal from many substances, including opiates and not limited to those cases that require pharmacological treatment. Medicaid covered more than half (52.6%) of all infants' births in the state of WV. The incidence of NAS was 85.8 and 12.7 per 1000 livebirths in the Medicaid and privately insured groups, respectively. Among all infants diagnosed with NAS, 86.1% were enrolled in the state's Medicaid programme. The risk of NAS in the Medicaid-insured newborns was higher than privately insured newborns in the unadjusted analysis (risk ratio (RR) 6.76, 95% confidence interval (CI) 5.95, 7.68) and the adjusted analysis RR 3.00, 95% CI 2.01, 4.49); adjusted risk difference 20.3 (95% CI 17.5, 23.1 cases per 1000 livebirths). NAS is an important indicator of the immediate effect of the opioid crisis. This study shows the disparity in NAS by health insurance status for a large rural population in the United States, and its burden on the state's Medicaid programme. Providing timely and accurate estimates of NAS is important for public health policies and decision making.


Quantitative trait loci affecting fertility and calving traits in Swedish dairy cattle.
Impaired fertility is the main reason for involuntary culling of dairy cows in Sweden. The objective of this study was to map quantitative trait loci (QTL) influencing fertility and calving traits in the Swedish dairy cattle population. The traits analyzed were number of inseminations, 56-d nonreturn rate, interval from calving to first insemination, fertility treatments, heat intensity score, stillbirth, and calving performance. A genome scan covering 20 bovine chromosomes was performed using 145 microsatellite markers. The mapping population consisted of 10 sires and their 417 sons in a granddaughter design. Nine of the sires were of the Swedish Red Breed, and one was a Swedish Holstein. Least squares regression was used to map loci affecting the analyzed traits, and permutation tests were used to set significance thresholds. Cofactors were used in the analyses of individual chromosomes to adjust for QTL found on other chromosomes. The use of cofactors increased both the number of QTL found and the significance level. In the initial analysis, we found 13 suggestive QTL that were mapped to chromosomes 6, 7, 9, 11, 13, 15, 20, and 29. When cofactors were included, 30 QTL were detected on chromosomes 1, 3, 4, 18, 19, 22, and 25, in addition to the 8 previously mentioned chromosomes. Some of the results from the cofactor analysis may be false positives and require further validation. In conclusion, we were able to map several QTL affecting fertility and calving traits in Swedish dairy cattle.


Animal welfare official inspections: farmers and inspectors shared concerns.
Official inspections to check the compliance of farms with European legislation to protect farm animals are often perceived negatively by farmers. In addition, the inspections have a limited effect on improving farm compliance. We looked at the perceptions of both farmers and their inspectors about animal welfare and the inspections in a case study of dairy production in France. The identification of gaps and commonalities between both parties should help us to propose improvements in the inspection method by which inspections could more likely encourage compliance with animal welfare legislation. To achieve this aim, we conducted semi-structured interviews with 22 dairy farmers and their 19 inspectors. Both farmers and inspectors described animal welfare in terms of the state of the animal and of the living conditions and care provided to them. The majority of farmers found that the official checklist used by the inspectors is inappropriate to assess the welfare of their animals; inspectors themselves reported that they often use their own criteria and indicators (often based on the observation of animals) in addition to the official checklist. Both groups disagreed with some requirements of the legislation. These findings suggest that the content and background of the legislation to protect animals should be made clearer to both farmers and inspectors and that these two groups of actors should be involved in the definition of key points to be checked on farms, with special attention to animal-based indicators. All this could improve farmers' engagement with the results of the inspections and, hopefully, could lead to better compliance with legislation and improvements in animal welfare on farms.


Multicenter trial of the PowerLink bifurcated system for endovascular aortic aneurysm repair.
The purpose of this study was to assess the results of abdominal aortic aneurysm repair with the PowerLink bifurcated endovascular graft (Endologix, Inc, Irvine, Calif). Twelve centers used the PowerLink bifurcated system for elective endovascular aneurysm repair in 118 patients recruited during a 16-month interval and followed for a 25-month interval (mean follow-up, 16 months) as part of a pivotal US Food and Drug Administration trial. Stent grafts were oversized by 10% to 20% relative to computed tomographic scan-based diameter measurements. All repairs were performed in the operating room through one surgically exposed femoral artery and a contralateral 9F sheath percutaneously placed. Results were assessed with contrast-enhanced computed tomography and plain abdominal radiography at 1, 6, and 12 months after surgery. Three failed insertions and one late conversion for endoleak remediation occurred, resulting in four conversions (3.3%) to open surgery. Of the failed insertions, two were from a faulty delivery system design, which was corrected. No failures occurred after the modification. One perioperative death (0.8%) occurred that was not device related. Eight late deaths were from unrelated causes, and one was from complications after reoperation for treatment of an endoleak. Endoleaks were noted in 19 patients (16%) at the time of the endograft procedure: 12 resolved spontaneously, four resolved with secondary interventions (three type I, one type II), and three underwent observation, yielding a 30-day endoleak rate of 5.9%. Two graft limb thromboses (0.8%) were seen. One graft migration (0.8%) was of no clinical significance. No ruptures or wire fractures were found. The mean aneurysm diameter was reduced from 51 mm (preoperative) to 45 mm (12 months; P <.0001). The PowerLink system appears to be safe and effectively protects patients from abdominal aortic aneurysm rupture over the short to medium term. The low endoleak rate is superior to that reported for other devices. The graft and stent materials have thus far been free from failure and fatigue. The sutureless stent and endoskeleton design confer a number of unique advantages and challenges. Careful follow-up over the longer term is necessary to assure the durability of these results.


Biological activity of the succinate dehydrogenase inhibitor fluopyram against Botrytis cinerea and fungal baseline sensitivity.
Succinate dehydrogenase inhibitors (SDHIs) constitute a fungicide class with increasing relevance in crop protection. These fungicides could play a crucial role in successful management of grey mould disease. In the present study the effect of fluopyram, a novel SDHI fungicide, on several developmental stages of Botrytis cinerea was determined in vitro, and the protective and curative activity against the pathogen was determined on strawberry fruit. Furthermore, fungal baseline sensitivity was determined in a set of 192 pathogen isolates. Inhibition of germ tube elongation was found to be the most sensitive growth stage affected by fluopyram, while mycelial growth was found to be the least sensitive growth stage. Fluopyram provided excellent protective activity against B. cinerea when applied at 100 µg mL(-1) 96, 48 or 24 h before the artificial inoculation of the strawberry fruit. Similarly, fluopyram showed a high curative activity when it was applied at 100 µg mL(-1) 24 h post-inoculation, but, when applications were conducted 48 or 96 h post-inoculation, disease control efficacy was modest or low. The measurement of baseline sensitivity showed that it was unimodal in all the populations tested. The individual EC(50) values for fluopyram ranged from 0.03 to 0.29 µg mL(-1). In addition, no correlation was found between sensitivity to fluopyram and sensitivity to other fungicides, including cyprodinil, fenhexamid, fludioxonil, iprodione, boscalid and pyraclostrobin. The obtained biological activity, baseline sensitivity and cross-resistance relationship data suggest that fluopyram could play a key role in grey mould management in the near future and encourage its introduction into spray programmes.


Past and present achievements, and future direction of the Gastrointestinal Oncology Study Group (GIOSG), a Division of Japan Clinical Oncology Group (JCOG).
Initially, Gastrointestinal Study Group in Japan Clinical Oncology Group (GIOSG/JCOG) focused on gastric cancer. In 1980s, fluoropyrimidine, cisplatin and mitomycin C were key drugs. A randomized Phase II trial (JCOG8501) comparing futrafur plus mitomycin C and uracil plus futrafur and mitomycin C showed a higher response rate of uracil plus futrafur and mitomycin C than futrafur plus mitomycin C. From the results of two Phase II trials of etoposide, adriamycin and cisplatin, and cisplatin plus 5-fluorouracil, uracil plus futrafur and mitomycin C and cisplatin plus 5-fluorouracil were adopted for the test arms of the Phase III trial (JCOG9205) comparing with continuous infusion of 5-fluorouracil as a control arm. Neither cisplatin plus 5-fluorouracil nor uracil plus futrafur and mitomycin C showed a survival benefit over continuous infusion of 5-fluorouracil. In late 1990s, new agents, irinotecan and S-1, were developed for gastric cancer in Japan. GIOSG conducted a Phase III trial (JCOG9912) investigating superiority of irinotecan plus cisplatin and non-inferiority of monotherapy with S-1 compared with continuous infusion of 5-fluorouracil, and S-1 succeeded in showing non-inferiority. Then, SPIRITS trial showed a survival benefit of S-1 plus cisplatin over S-1, resulting in the establishment of a standard care for advanced gastric cancer in Japan. GIOSG have merged with Gastric Cancer Study Group as the Stomach Cancer Study Group (SCSG) from 2011. Recent progress in the development of new drugs has been remarkable. From the point of the roles shared with many other study groups for clinical trials, including registration trials of new drugs conducted by pharmaceutical companies, SCSG should recognize its role and conduct clinical trials with high quality for establishing new standard treatment.


Biogas Digester Hydraulic Retention Time Affects Oxygen Consumption Patterns and Greenhouse Gas Emissions after Application of Digestate to Soil.
Knowledge about environmental impacts associated with the application of anaerobic digestion residue to agricultural land is of interest owing to the rapid proliferation of biogas plants worldwide. However, virtually no information exists concerning how soil-emitted NO is affected by the feedstock hydraulic retention time (HRT) in the biogas digester. Here, the O planar optode technique was used to visualize soil O dynamics following the surface application of digestates of the codigestion of pig slurry and agro-industrial waste. We also used NO isotopomer analysis of soil-emitted NO to determine the NO production pathways, i.e., nitrification or denitrification. Two-dimensional images of soil O indicated that anoxic and hypoxic conditions developed at 2.0- and 1.5-cm soil depth for soil amended with the digestate produced with 15-d (PO15) and 30-d (PO30) retention time, respectively. Total NO emissions were significantly lower for PO15 than PO30 due to the greater expansion of the anoxic zone, which enhanced NO reduction via complete denitrification. However, cumulative CO emissions were not significantly different between PO15 and PO30 for the entire incubation period. During incubation, NO emissions came from both nitrification and denitrification in amended soils. Increasing the HRT of the biogas digester appears to induce significant NO emissions, but it is unlikely to affect the NO production pathways after application to soil.


[Functional pathophysiology of consciousness].
Consciousness (Latin conscientia "moral conscience"), according to the English philosopher John Locke (1632-1704) [103], is the awareness of all that occurs in the mind of a person, whereas the American philosopher John Searle (2000) defined it as "inner qualitative, subjective states and processes of awareness". In modern science it is defined as a continuous state of full awareness of the Self and one's relationship to the external and internal environment, describing the degree of wakefulness in which an organism recognizes stimuli. This widely discussed biological term for complex neuronal processes that allow an individuum to recognize itself and its environment and to act accordingly, has been and still is the subject of much research in philosophy and natural/neuroscience. Its definition is often used for awareness and recognition, too. While the Egyptians in the papyrus Edwin Smith already recognized the brain as the seat of consciousness, René Descartes (1644 [36]) believed its special structure should be "a small gland in the middle", but the anatomical structures and physiological processes involved in consciousness were elucidated only in the middle of the 20th century. Neuronal substrates include several functional networks that are hierarchically organized and cooperate functionally. The lowest level is the mesencephalic formatio reticularis and its projections to the thalamus that were identified als ascending reticular system (ARAS) by the classical experiments of Moruzzi and Magoun, whereas later analyses of patients with impaired consciousness provided further insights. The mesencephalic ARAS as motor of the function of higher structures projects 1. via the reticular thalamus diffusely to the cortex, 2. via hypothalamus to the basal forebrain and limbic system, and 3. to the medial raphe of the brainstem and locus coeruleus and their diffuse cortical projections. The reticular system is stimulated directly and indirectly via numerous collaterals from important somatic and sensory pathways and acts as a control system of neuronal activities of the cerebral cortex. The principal function of the ARAS is to focus our alertness on specific stimuli or internal processes, which run via complex neuronal cell groups and numerous neurotransmitters that influence various aspects of consciousness and wakefulness. Stimulation of the ARAS produces an arousal reaction as the electric correlate of consciousness; its destruction causes coma and related states. The highest level are cortical (prefrontal and association) networks for recognition, motor activity, longterm memory and attention, the left hemisphere being considered as the dominant one. Different levels of consciousness are distinguished: 1. hyperalertness, 2. alertness (normal state of wakefulness), 3. somnolence or lethargy, 4. obtundation with tendency to fall asleep, 5. stupor, 6. coma and its subtypes, like akinetic mutism, apallic syndrome or persistent vegative state, locked-in syndrome, delirium, and catatonia. They are caused by damages in various functional levels of the brain, by psychogenic factors or experimentally, and are accompanied by characteristic neurological and psychiatric disorders. The relevant morphological lesions can be detected by electrophysiological and imaging studies. The bases of functional anatomy and pathophysiology of consciousness, its cognitive aspects and its major disorders, their causes and functional substrates with reference to sleep and both spontaneous and iatrogenic disorders of consciousness are critically summarized.


Pharmacological Effects and Underlying Mechanisms of Licorice-Derived Flavonoids.
Glycyrrhizae Radix et Rhizoma is the most frequently prescribed natural medicine in China and has been used for more than 2,000 years. The flavonoids of licorice have garnered considerable attention in recent decades due to their structural diversity and myriad pharmacological effects, especially as novel therapeutic agents against inflammation and cancer. Although many articles have been published to summarize different pharmacological activities of licorice in recent years, the systematic summary for flavonoid components is not comprehensive. Therefore, in this review, we summarized the pharmacological and mechanistic data from recent researches on licorice flavonoids and their bioactive components.


Fine needle aspiration cytology of the thyroid in children and adolescents: experience with 792 aspirates.
To determine the distribution of thyroid lesions in pediatric and adolescent patients in Kuwait. During a 16-year period (January 1993-December 2008) the cytology reports of 792 thyroid aspirates (724 females and 68 males) performed on children and adolescents (ranging from 4 to 21 years) at Mubarak Al-Kabeer Hospital were reviewed. Of these 62, 150, 201 and 379 aspirates belonged to the age group 4-- <12, 12-- <16, 16-- <19 and 19-21 years, respectively. There were 745 satisfactory aspirates (678 [91%] females and 67 [9%] males). The unsatisfactory rate was 5.9%, with 51.1% of the unsatisfactory aspirates in the 19-21 age group. Benign cytology was reported in 578 cases (77.6%), with 522 (70.1%) aspirates from females and 56 (7.5%) from males. Chronic lymphocytic thyroiditis was observed in 121 cases (16.2%), and 7 of these were males. Papillary carcinoma was detected in 20 (2.7%), and 4 of these were males. Suspicious cytology was reported only in females and comprised 7 cases (0.9%) with a suspicion of papillary carcinoma and 19 cases (2.6%) with a follicular lesion. Fine needle aspiration cytology of children's and adolescents' thyroid nodules is feasible and reliable. The majority of the nodules in this age group are benign, and fine needle aspiration cytology helps prevent unnecessary surgery.


Acute and chronic exercise training in patients with Class II pulmonary hypertension: effects on haemodynamics and symptoms.
More than half of heart failure (HF) patients have concomitant pulmonary hypertension, impacting symptoms and prognosis. The role of exercise in this category of patients is still unclear, probably because of the lack of a clear relationship between exercise and acute and chronic pulmonary artery pressure variations and related changes in symptoms. The limited evidence on this topic is contradictory and hardly comparable due to use of different exercise programmes and pulmonary artery pressure assessment techniques. This is further compounded by different functional and structural classes of HF making definite assessments and interpretations of exercise effect on outcomes difficult. Exercise training programmes were proven beneficial in HF patients; however, the lack of data about their pulmonary haemodynamic effects prevents clear indications on the best exercise types for patients presenting secondary pulmonary hypertension and different HF categories. Indeed, some data suggest that not all HF patients have similar responses to training, leading to either beneficial or detrimental effects, depending on the HF type. Future studies, involving modern technologies such as continuous pulmonary artery pressure monitoring implantable devices, may clarify the current gaps in this field, aiming at patient-tailored exercise training rehabilitation programmes, in order to improve clinical outcomes, quality of life, and hopefully prognosis.


Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression.
Anhedonia--which is defined as diminished pleasure from, or interest in, previously rewarding activities-is one of two cardinal symptoms of a major depressive episode. However, evidence suggests that standard treatments for depression do little to alleviate the symptoms of anhedonia and may cause reward blunting. Indeed, no therapeutics are currently approved for the treatment of anhedonia. Notably, over half of patients diagnosed with bipolar disorder experience significant levels of anhedonia during a depressive episode. Recent research into novel and rapid-acting therapeutics for depression, particularly the noncompetitive N-Methyl-D-aspartate receptor antagonist ketamine, has highlighted the role of the glutamatergic system in the treatment of depression; however, it is unknown whether ketamine specifically improves anhedonic symptoms. The present study used a randomized, placebo-controlled, double-blind crossover design to examine whether a single ketamine infusion could reduce anhedonia levels in 36 patients with treatment-resistant bipolar depression. The study also used positron emission tomography imaging in a subset of patients to explore the neurobiological mechanisms underpinning ketamine's anti-anhedonic effects. We found that ketamine rapidly reduced the levels of anhedonia. Furthermore, this reduction occurred independently from reductions in general depressive symptoms. Anti-anhedonic effects were specifically related to increased glucose metabolism in the dorsal anterior cingulate cortex and putamen. Our study emphasizes the importance of the glutamatergic system in treatment-refractory bipolar depression, particularly in the treatment of symptoms such as anhedonia.


Cartilage repair in a rat model of osteoarthritis through intraarticular transplantation of muscle-derived stem cells expressing bone morphogenetic protein 4 and soluble Flt-1.
The control of angiogenesis during chondrogenic differentiation is an important issue affecting the use of stem cells in cartilage repair, especially with regard to the persistence of regenerated cartilage. This study was undertaken to investigate the effect of vascular endothelial growth factor (VEGF) stimulation and the blocking of VEGF with its antagonist, soluble Flt-1 (sFlt-1), on the chondrogenesis of skeletal muscle-derived stem cells (MDSCs) in a rat model of osteoarthritis (OA). We investigated the effect of VEGF on cartilage repair in an immunodeficiency rat model of OA after intraarticular injection of murine MDSCs expressing bone morphogenetic protein 4 (BMP-4) in combination with MDSCs expressing VEGF or sFlt-1. In vivo, a combination of sFlt-1- and BMP-4-transduced MDSCs demonstrated better repair without osteophyte formation macroscopically and histologically following OA induction, when compared with the other groups. Higher differentiation/proliferation and lower levels of chondrocyte apoptosis were also observed in sFlt-1- and BMP-4-transduced MDSCs compared with a combination of VEGF- and BMP-4-transduced MDSCs or with BMP-4-transduced MDSCs alone. In vitro experiments with mixed pellet coculture of MDSCs and OA chondrocytes revealed that BMP-4-transduced MDSCs produced the largest pellets, which had the highest gene expression of not only type II collagen and SOX9 but also type X collagen, suggesting formation of hypertrophic chondrocytes. Our results demonstrate that MDSC-based therapy involving sFlt-1 and BMP-4 repairs articular cartilage in OA mainly by having a beneficial effect on chondrogenesis by the donor and host cells as well as by preventing angiogenesis, which eventually prevents cartilage resorption, resulting in persistent cartilage regeneration and repair.


Self-assembling a 1,4-dioxane-degrading consortium and identifying the key role of Shinella sp. through dilution-to-extinction and reculturing.
Assembling a functional microbial consortium and identifying key degraders involved in the degradation of 1,4-dioxane are crucial for the design of synergistic consortia used in enhancing the bioremediation of 1,4-dioxane-contaminated sites. However, due to the vast diversity of microbes, assembling a functional consortium and identifying novel degraders through a simple method remain a challenge. In this study, we reassembled 1,4-dioxane-degrading microbial consortia using a simple and easy-to-operate method by combining dilution-to-extinction and reculture techniques. We combined differential analysis of community structure and metabolic function and confirmed that Shinella species have a stronger 1,4-dioxane degradation ability than Xanthobacter species in the enriched consortium. In addition, a new dioxane-degrading bacterium was isolated, Shinella yambaruensis, which verified our findings. These results demonstrate that DTE and reculture techniques can be used beyond diversity reduction to assemble functional microbial communities, particularly to identify key degraders in contaminant-degrading consortia.


Fragile X-Associated Neuropsychiatric Disorders (FXAND).
Fragile X syndrome (FXS) is caused by the full mutation (>200 CGG repeats) in the Fragile X Mental Retardation 1 (FMR1) gene. It is the most common inherited cause of intellectual disability (ID) and autism. This review focuses on neuropsychiatric disorders frequently experienced by premutation carriers with 55 to 200 CGG repeats and the pathophysiology involves elevated FMR1 mRNA levels, which is different from the absence or deficiency of fragile X mental retardation protein (FMRP) seen in FXS. Neuropsychiatric disorders are the most common problems associated with the premutation, and they affect approximately 50% of individuals with 55 to 200 CGG repeats in the FMR1 gene. Neuropsychiatric disorders in children with the premutation include anxiety, ADHD, social deficits, or autism spectrum disorders (ASD). In adults with the premutation, anxiety and depression are the most common problems, although obsessive compulsive disorder, ADHD, and substance abuse are also common. These problems are often exacerbated by chronic fatigue, chronic pain, fibromyalgia, autoimmune disorders and sleep problems, which are also associated with the premutation. Here we review the clinical studies, neuropathology and molecular underpinnings of RNA toxicity associated with the premutation. We also propose the name Fragile X-associated Neuropsychiatric Disorders (FXAND) in an effort to promote research and the use of fragile X DNA testing to enhance recognition and treatment for these disorders.


Pharmacokinetics screening for multi-components absorbed in the rat plasma after oral administration traditional Chinese medicine formula Yin-Chen-Hao-Tang by ultra performance liquid chromatography-electrospray ionization/quadrupole-time-of-flight mass spectrometry combined with pattern recognition methods.
Traditional Chinese medicine (TCM) has been widely used in many oriental countries for thousands of years and played an indispensable role in the prevention and treatment of diseases, especially the complicated and chronic ones. It is a very complex mixture containing hundreds or thousands of different components. Pharmacokinetic study on active constituents in TCM preparations is a good way for us to explain and predict a variety of events related to the efficacy and toxicity of TCM. A selective and sensitive method of ultra performance liquid chromatography coupled with electrospray ionization/quadrupole-time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) was first developed to screen the potentially bioactive components in vivo, using the semi-quantitative determination of multicomponents in the rat plasma after a single oral administration of Yin-Chen-Hao-Tang (YCHT), a famous TCM formula for liver disorders. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were built to evaluate the differences of pharmacokinetic behaviors (time-course) of the absorbed components of YCHT. Here, we report that the developed method was successfully applied to monitoring the pharmacokinetic time-course of 21 compounds in rat plasma, and were grouped in 3 separate clusters using pattern recognition approaches (both HCA and PCA). Comparing the body dynamics of each composition, the initial choice of the following 9 compounds as the candidate components was: 7-methoxycoumarin-6-hydroxyl sulfate, genipingentiobioside, geniposide, 6,7-dimethylesculetin, peak 16, chimaphylin, 6-dementhoxycapillarisin, capillarisin, rhein. Pharmacokinetics based-UPLC-ESI-Q-TOF-MS/MS combined with HCA and PCA approaches can provide a reliable and suitable means of identifying and screening potentially bioactive components contributing to pharmacological effects of TCM, further prospecting natural products in the search for new leads in drug discovery.


Production of melanin pigments by chemical and enzymatic oxidation of tetrahydroisoquinolines.
Tetrahydropapaveroline (THP) oxidation was studied in various experimental conditions by absorbance spectroscopy. THP was found to be easily oxidized by mushroom tyrosinase, giving rise to the formation of a chromophore (THP-chrome) with absorption maxima at 308 and 470 nm. The oxidation further proceeds leading to the formation of a melanin-like pigment. The use of periodate as oxidant at pH 7.4 allows the visualization of the THP-chrome, as well. Other tetrahydroisoquinolines bearing a catechol moiety, such as salsolinol, laudanosoline and apomorphine, have been found to be easily oxidized in the same conditions, giving rise to pigmented derivatives. The products of THP oxidation are able to copolymerize with dopa or opioid peptides in the presence of tyrosinase, generating mixed-type melanins.


Simplified magnetic anchor-guided endoscopic submucosal dissection: an ex vivo porcine model.
Endoscopic submucosal dissection (ESD) is a well-established treatment for superficial gastrointestinal tumors and enables en bloc resection. Adequate tissue tension is important for safe and effective dissection. Simplified magnetic anchor-guided ESD (MAG-ESD) with a neodymium magnet has potential benefits, compared with other current traction methods. We evaluated the feasibility of simplified MAG-ESD in an ex vivo porcine model. An experimental study was conducted, utilizing the standard ESD technique. An external magnet and an internal magnet, both neodymium magnets, were used for the magnetic anchoring. The internal magnet was attached to an arm of a hemoclip with a 2-0 silk suture. After the incision, the clip with the internal magnet was placed at the edge of the lesion. The external magnet was maneuvered around the surface to apply adequate tension. A total of 15 en bloc ESDs (five with no magnetic anchoring and 10 with magnetic anchoring) were carried out. Traction and dissection were feasible in all cases and the procedures were completed in fewer than 90 min. Lesion size ranged from 15 to 50 mm (mean 30 mm). Two cases in the group with magnetic anchoring presented with punctate perforation (13.3%). Our study demonstrated the feasibility of simplified MAG-ESD and en bloc resection in an ex vivo porcine model.


Mutations in the newly identified RAX regulatory sequence are not a frequent cause of micro/anophthalmia.
Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. A few genes (SOX2, OTX2, RAX, and CHX10) have been implicated in isolated micro/anophthalmia, but causative mutations of these genes explain less than a quarter of these developmental defects. A specifically conserved SOX2/OTX2-mediated RAX expression regulatory sequence has recently been identified. We postulated that mutations in this sequence could lead to micro/anophthalmia, and thus we performed molecular screening of this regulatory element in patients suffering from micro/anophthalmia. Fifty-one patients suffering from nonsyndromic microphthalmia (n = 40) or anophthalmia (n = 11) were included in this study after negative molecular screening for SOX2, OTX2, RAX, and CHX10 mutations. Mutation screening of the RAX regulatory sequence was performed by direct sequencing for these patients. No mutations were identified in the highly conserved RAX regulatory sequence in any of the 51 patients. Mutations in the newly identified RAX regulatory sequence do not represent a frequent cause of nonsyndromic micro/anophthalmia.


Reconstitution of lymphoid tissues under the influence of a subclinical level of graft versus host reaction induced by bone marrow T cells or splenic T cell subsets.
Reconstitution of lymphoid tissues under the influence of subclinical graft versus host reaction (GVHR) has been investigated. Lethally irradiated AKR mice were reconstituted with B10 bone marrow (BM) cells which had been treated with anti-Thy-1 antibody alone without complement (GVHR chimera). Their immunological reconstitution was analyzed and compared with that of AKR recipients which had been reconstituted with B10 BM cells treated with anti-Thy-1 antibody plus complement (control chimera). One hundred percent of both chimeras survived more than 100 days without showing clinical signs of GVHR. However, full donor chimerism was accomplished at an early stage after reconstitution in the former GVHR chimeras, whereas a substantial number of recipient T cells persisted in control chimeras for the entire observation period. When reconstitution of various lymphoid tissues was compared between control and GVHR chimeras, no difference in the reconstitution of the thymus and spleen was noted. By contrast, the cellularity of peripheral lymph nodes in GVHR chimeras was regularly considerably lower than that of the control chimeras. The apparent insufficiency of lymph node reconstitution appeared to be attributable to the impairment of lymph node structure itself which may be involved in lymphocyte homing. Furthermore, clonal deletion of V beta 6+ T cells which are reactive to recipient (Mls-1a) antigens was abrogated in the GVHR chimeras but was normally induced in the more completely T cell-depleted control chimeras. This abrogation of clonal deletion of V beta 6+ T cells appeared to result from the early disappearance of recipient T cells in these chimeras. Thus, it appeared that donor T cells in the BM that survive anti-Thy-1 treatment in vitro plus subsequent BM transplantation induced a subclinical level GVHR which contributed to the full donor chimerism as well as abrogation of clonal elimination of V beta 6+ donor T cells. Indeed, inoculation of CD8+ T cells along with the transplantation of the T cell-depleted BM cells (anti-Thy-1 plus C-treated cells) from donor mice into the AKR recipients was also shown to induce a similar state in the recipients.


Identification of 16S rRNA mutations in Mycoplasma genitalium potentially associated with tetracycline resistance in vivo but not selected in vitro in M. genitalium and Chlamydia trachomatis.
Tetracyclines are widely used for the treatment of bacterial sexually transmitted infections (STIs) and recently have been used successfully for post-exposure prophylaxis of STIs in MSM. We investigated the in vitro and in vivo development of tetracycline resistance in Chlamydia trachomatis and Mycoplasma genitalium and evaluated 16S rRNA mutations associated with acquired resistance in other bacteria. In vitro selection of resistant mutants of reference strains of C. trachomatis and M. genitalium was undertaken by serial passage in medium containing subinhibitory concentrations of tetracycline or doxycycline, respectively. The 16S rRNA gene of the two microorganisms was amplified and sequenced at different passages, as were those of 43 C. trachomatis- and 106 M. genitalium-positive specimens collected in France from 2013 to 2019. No tetracycline- or doxycycline-resistant strains of C. trachomatis and M. genitalium, respectively, were obtained after 30 serial passages. The tetracycline and doxycycline MICs were unchanged and analysis of the 16S rRNA gene, the molecular target of tetracyclines, of C. trachomatis and M. genitalium revealed no mutation. No mutation in the 16S rRNA gene was detected in C. trachomatis-positive specimens. However, six M. genitalium-positive specimens harboured a mutation potentially associated with tetracycline resistance without known prior tetracycline treatment for patients. Tetracyclines did not select in vitro-resistant mutants of C. trachomatis or M. genitalium. However, 16S rRNA mutations either responsible for or associated with tetracycline resistance in other bacteria, including mycoplasma species, were identified in several M. genitalium-positive specimens.


A space-efficient algorithm for the constrained pairwise sequence alignment problem.
The constrained pairwise sequence alignment (CPSA) problem aims to align two given sequences by aligning their similar subsequences in the same region under the guidance of a given pattern (constraint). Let the lengths of the sequences be m, and n where n <or= m, and let r <or= n be the length of the given pattern. The optimum constrained pairwise alignment score can be computed using O(rn) space by a naive dynamic programming solution. If an optimal alignment path is desired then the space requirement of the naive dynamic programming algorithm is O(rnm). There is a divide-and-conquer algorithm that reduces the memory requirement of finding an optimal alignment for the CPSA problem to O(rn). In this paper, we present a space-efficient CPSA algorithm that returns an optimal alignment. Our analysis on real protein sequences suggests that our algorithm requires only O(n) space in practice. This algorithm is not only space efficient but also very fast. A generalization of the CPSA problem for multiple sequences is called the constrained multiple sequence alignment (CMSA) problem. Our CPSA algorithm also improves the space requirement of progressive CMSA algorithms that use solutions of CPSA problems.


Determination of phenolic constituents in citrus samples by on-line coupling of a flow system with capillary electrophoresis.
Phenolic compounds extracted from different citrus were determined. Calibration, extraction, elution, and introduction into the sample vial was carried out automatically by a continuous flow system (CFS) coupled to capillary electrophoresis (CE) equipment via a programmable arm. The only manual operation was the centrifugation of the sample to remove the pulp. The supernatant solutions were introduced into the CFS-CE system. A C-18 minicolumn coupled into the CFS was used to perform cleanup of the samples. The analytes were eluted from the minicolumn using methanol. Quantitative analysis was carried out by the standard addition method. The method presented allows a fast, quantitative, and reproducible determination of six main phenolic compounds in citrus samples, with precision in the range of 3.0-6.5%, expressed as relative standard deviations.


Tuning CO2 Capture at the Gas/Amine Solution Interface by Changing the Solvent Polarity.
Carbon dioxide scrubbing by aqueous amine solution is considered as a promising technology for post-combustion CO2 capture, while mitigating climate change. The lack of physicochemical details for this process, especially at the interface between the gas and the condensed phase, limits our capability in designing novel and more cost-effective scrubbing systems. Here, we present classical and first-principles molecular dynamics results on CO2 capture at the gas/amine solution interfaces using solvents of different polarities. Even if it is apolar, carbon dioxide is absorbed at the gas/monoethanolamine (MEA) aqueous solution interface, forming stable and interfacial [CO2·MEA] complexes, which are the first reaction intermediate toward the chemical conversion of CO2 to carbamate ions. We report that the stability of the interfacial [CO2·MEA] precomplex depends on the nature and polarity of the solution, as well as on the conformer population of MEA. By changing the polarity of the solvent, using chloroform, we observed a shift in the interfacial MEA population toward conformers that form more stable [CO2·MEA] complexes and, at the same time, a further stabilization of the complex induced by the solvent environment. Thus, while lowering the polarity of the solvent could decrease the solubility of MEA, at the same time, it favors conformers that are more prone to CO2 capture and mineralization. The results presented here offer a theoretical framework that helps in designing novel and more cost-effective solvents for CO2 scrubbing systems, while shedding further light on the intrinsic reaction mechanisms of interfacial environments in general.


Tragic case of a dog bite in a young child: the dog stands trial.
The authors present the tragic case of an 18-month-old child who was bitten by a dog, causing amputation of the forearm and substantial damage to the cutaneous muscle on his back, shoulder, thorax, and neck. A free latissimus dorsi flap was performed to preserve the humerus from which the periosteum had been torn away. A series of cutaneous expansions were then undertaken to graft skin back onto the back, the armpit, and the shoulder stump, to allow for a mechanical prosthesis. A study of the literature on this subject proves that dog bites are more frequent and serious (sometimes even fatal) in young children than in adults. In view of the current legislation, it would seem that the public health authorities are doing little to resolve this distressing problem.


Identification of Nitrogen Use Efficiency Genes in Barley: Searching for QTLs Controlling Complex Physiological Traits.
Over the past half century, the use of nitrogen (N) fertilizers has markedly increased crop yields, but with considerable negative effects on the environment and human health. Consequently, there has been a strong push to reduce the amount of N fertilizer used by maximizing the nitrogen use efficiency (NUE) of crops. One approach would be to use classical genetics to improve the NUE of a crop plant. This involves both conventional breeding and quantitative trait loci (QTL) mapping in combination with marker-assisted selection (MAS) to track key regions of the chromosome that segregate for NUE. To achieve this goal, one of initial steps is to characterize the NUE-associated genes, then use the profiles of specific genes to combine plant physiology and genetics to improve plant performance. In this study, on the basis of genetic homology and expression analysis, barley candidate genes from a variety of families that exhibited potential roles in enhancing NUE were identified and mapped. We then performed an analysis of QTLs associated with NUE in field trials and further analyzed their map-location data to narrow the search for these candidate genes. These results provide a novel insight on the identification of NUE genes and for the future prospects, will lead to a more thorough understanding of physiological significances of the diverse gene families that may be associated with NUE in barley.


Probiotic pre-administration reduces mortality in a mouse model of cecal ligation and puncture-induced sepsis.
A number of clinical trials have demonstrated that the use of probiotics has the potential to prevent nosocomial infections. However, the mechanism underlying probiotic-induced anti-infection and sepsis remains to be investigated. In the present study, 200 µl/day of Lactobacillus rhamnosus GG (LGG) or normal saline (control) was orally administrated to 4-week-old C57BL6 mice 4 weeks prior to cecal ligation and puncture (CLP). A number of mice were sacrificed 24 h after CLP, and the remaining mice were used for survival studies. Ileum tissues were collected to evaluate the injury on the intestine. Blood samples were also obtained to investigate the changed metabolic pattern in mice that underwent different treatments using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). In the survival studies, the mortality of CLP-induced septic mice pretreated with LGG was significantly lower compared with untreated mice (P=0.029). Ileum mucosal damage was evident in the control septic mice. Based on the data of UPLC-QTOF-MS, phosphatidylcholines were increased and lysophosphatidylcholines (LPCs) that contained polyunsaturated fatty acids were decreased in septic mice, whereas saturated fatty acid LPCs reveal no significant difference between septic and sham mice. In addition, the metabolic profile in the septic mice pretreated with LGG was much closer to that of sham mice compared with control septic mice. The results of the present study suggest that probiotic pre-administration reduces the mortality in septic mice by decreasing ileum mucosal damage, increasing the gut barrier integrity and altering global serum metabolic profiles.


Socially biased learning among adult cottontop tamarins (Saguinus oedipus).
We presented adult cottontop tamarins (Saguinus oedipus) with a novel foraging task that had been used previously to examine socially biased learning of juvenile observers [Humle & Snowdon, Animal Behaviour 75:267-277, 2008]. The task could be solved in one of two ways, and thus allowed for an analysis of behavioral matching between an observer and a skilled demonstrator (trained to use one of the two methods exclusively). Because the demonstrator was an adult in both this study and the juvenile study, the influence of the observer's age could be isolated and examined, as well as the behavior of demonstrators toward observers of different ages. Our main goals were to (1) compare adults and juveniles acquiring the same task to identify how the age of the observer affects socially biased learning and (2) examine the relationship between socially biased learning and behavioral matching in adults. Although adults spent less time observing the trained demonstrators than did juveniles, the adults were more proficient at solving the task. Furthermore, even though observers did not overtly match the behavior of the demonstrator, observation remained an important factor in the success of these individuals. The findings suggested that adult observers could extract information needed to solve a novel foraging task without explicitly matching the behavior of the demonstrator. Adult observers begged much less than juveniles and demonstrators did not respond to begging from adult. Skill acquisition and the process of socially biased learning are, therefore, age-dependent and are influenced by the behavioral interactions between observer and demonstrator. To what extent this holds true for other primates or animal species still needs to be more fully investigated and considered when designing experiments and interpreting results.


Observational comparisons of intestinal microbiota characterizations, immune enzyme activities, and muscle amino acid compositions of loach in paddy fields and ponds in Sichuan Province.
A balanced intestinal microbial ecosystem is crucial for the growth and health of animals because it can influence the digestion and absorption of nutrients in the intestine. Different culture conditions may change the ecology of microbial in intestine and thus affect the overall growth performance of an animal. In this study, we compared intestinal morphologies, microbiota characterizations, immune enzyme activities, and muscle amino acid compositions of loach cultured in paddy fields and ponds. The fish were fed with the same diets from May 5 to November 5 (2015) in three paddy or ponds. Fish samples were collected for analysis in the August (summer season) and November (fall season) during the feeding trial. In both culture conditions, results based on microscopy observation showed that the intestinal perimeter, fold height, fold radical, and total absorption of the gut were significantly higher in the foregut than that found in the midgut and hindgut (P < 0.01). The average final body weight of fish was similar between the two culture conditions (P > 0.05). The percentage of carcass weight to whole loach weight for samples collected from paddy field (91.6 ± 1.1) was significantly higher than the index measured for loach from pond (87.3 ± 3.4, P < 0.05). Results based on denaturing gradient gel electrophoresis demonstrated that the Shannon-diversity index, evenness, and richness of intestinal flora were increased from summer to fall in paddy cultivation. In pond culture condition, however, the above indexes obtained from mucosa and intestinal contents decreased in fish from summer to fall. The sequencing results of bands indicated that the predominant microorganisms are Proteobacteria, Firmicutes, and Actinobacteria in the intestine of fish being cultured in both cultures. Activities of alkaline phosphatase (AKP, in two culture conditions) and superoxide dismutase (SOD, in paddy field) presented a gradual decrease trend from foregut to hindgut of fish. The activities of acid phosphatase (ACP, in midgut), AKP (in midgut and hindgut), SOD (in foregut), and lysozyme (LZM, in midgut) were significantly higher in fish cultured in paddy than those in pond (P < 0.01). In addition, the percentage of some essential amino acids (valine, methionine, and phenylalanine) based on total amino acids in muscle was significantly higher in fish cultured in paddies than in ponds. In summary, the fish cultured in paddy or pond was not significantly different in growth but the two culture conditions seems to generate different carcass yield and changed the amino acid profiles of fish muscle. The similar predominance microorganisms were identified in the intestine of fish from two conditions, and the quantification of microbial in the intestine will be determined in the future, but part activities involved in immune protection were higher for fish cultured in paddy fields.


Genetics and criminal behaviour: recent accomplishments.
The past two decades have seen an explosion in research in the fields of violence and behavioural genetics. Advances in human genetics have raised the possibility that genetic mechanisms can explain various aspects of human criminal and aggressive behaviour. However, this new knowledge can pose enormous challenges concerning the moral and legal conceptions of free will and responsibility. This paper reviews the main aspects of behavioural genetics, focusing on criminal and aggressive behaviour and describes the most important genes known to influence this behaviour.


Methodical studies for d/h-isotope analysis - a new technique for the direct coupling of sample preparation to an irms.
Abstract A new technique for the sample preparation and direct coupling to an Isotope Ratio Mass Spectrometer (IRMS) for the D/H-determination is described. 1 μl size samples of water are injected and reduced with chromium metal in a novel reaction furnace. The hydrogen gas flows directly into the IRMS and is analysed (standard/sample comparison). The reproducibility is about 1 %. The accuracy of the technique was proven by means of the IAEA-standard waters V-SMOW, GISP, SLAP.


Manipulation of aqueous growth of CdTe nanocrystals to fabricate colloidally stable one-dimensional nanostructures.
The present article is devoted to systematically exploring the influence of various experimental variables, including the precursor concentration, the ligand nature, the counterion type, the Cd-to-Te molar ratio, pH, and temperature, on the aqueous growth of CdTe nanocrystals. The growth may be divided into two stages: the early fast growth stage and the later slow growth stage. The later stage is found to be dominated by Ostwald ripening (OR), being strongly dependent on all experimental conditions. In contrast, the early stage is dominated by adding monomers to nanocrystals, which may be dramatically accelerated by lowering precursor concentrations and using ligands with a molecular structure similar to that of thioglycolic acid (TGA). This fast growth stage is similar to that observed during organometallic growth of nanocrystals in hot organic media. On the basis of this finding, one-dimensional wurtzite CdTe nanostructures can be directly prepared in aqueous media by storing rather dilute precursor solution (2.4 mM with reference to ligand) in the presence of TGA at lower temperature (from room temperature to 80 degrees C). A low growth temperature is used to suppress OR during crystal growth. In addition, the simultaneous presence of both TGA-like ligand and 1-thioglycerol or 2-mercaptoethylamine leads to formation of colloidally stable 1D CdTe nanostructures with controlled aspect ratios.


Coronavirus disease 2019 (COVID-19) vaccine platforms: how novel platforms can prepare us for future pandemics: a narrative review.
More than 2 years after the explosion of the coronavirus disease 2019 (COVID-19) pandemic, extensive efforts have been made to develop safe and efficacious vaccines against infections with severe acute respiratory syndrome coronavirus 2. The pandemic has opened a new era of vaccine development based on next-generation platforms, including messenger RNA (mRNA)-based technologies, and paved the way for the future of mRNA-based therapeutics to provide protection against a wide range of infectious diseases. Multiple vaccines have been developed at an unprecedented pace to protect against COVID-19 worldwide. However, important knowledge gaps remain to be addressed, especially in terms of how vaccines induce immunogenicity and efficacy in those who are elderly. Here, we discuss the various vaccine platforms that have been utilized to combat COVID-19 and emphasize how these platforms can be a powerful tool to react quickly to future pandemics.


[Range of motion in the joints of the upper extremity at different stages of sympathetic reflex dystrophy (SRD)].
Sympathetic reflex dystrophy of the upper extremity is among the most serious complications of trauma injuries. The aim of this paper was to assess the effectiveness of mobilization treatment, augmented by cryogenic temperatures of post trauma SRD of the upper extremity. The material comprised 113 patients treated at the Orthopedic Outpatient Clinic of the J. Babiński Hospital in Breslau during the years 1987-1995. All patients underwent conservative treatment because of post trauma SRD. The effectiveness of cryo-therapy was based on pre- and post-therapy ROM examination. These results were compared to the ROM of the healthy extremity and the degree of ROM limitation was hence calculated. Limitation of ROM was found in all joints of the upper extremity regardless to the stage of the disease. The greatest limitations were found in the joints directly adjacent to the area were the disease was most pronounced. The applied therapy in these cases was found to increase ROM in all patients, with the greatest increase of ROM during stage I and II of the disease.


Heme oxygenase-1-dependent and -independent regulation of angiogenic genes expression: effect of cobalt protoporphyrin and cobalt chloride on VEGF and IL-8 synthesis in human microvascular endothelial cells.
Induction of heme oxygenase-1 (HO-1) expression can be achieved by stimulation with cobalt protoporphyrin (CoPPIX) or cobalt chloride (CoCl2). HO-1 has been recently implicated in regulation of angiogenesis and CoCl2 is known to potently activate hypoxia inducible factor-1 (HIF-1) transcription factor, a key regulator of angiogenic response in hypoxia. Here we determined the effect of CoPPIX and CoCl2 on the expression of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), the two major angiogenic mediators, in human microvascular endothelial cells (HMEC-1). CoPPIX induced HO-1 expression and strongly enhanced VEGF and IL-8 synthesis, through the activation of VEGF and IL-8 promoters. Inhibition of HO activity by SnPPIX decreased VEGF production, while, interestingly, it did not affect IL-8. CoCl2 activated hypoxia-responsive element (HRE) and consequently VEGF generation via the enhancement of production of reactive oxygen species (ROS). On the other hand, CoCl2 did not influence IL-8 expression, while CoPPIX did not induce ROS elevation neither it affected HRE activity in VEGF promoter. Our data show that although both CoCl2 and CoPPIX induce HO-1, the influence of CoCl2 on VEGF does not involve HO-1 and is HIF-1-dependent, while the effect of CoPPIX does not involve HIF-1 but relies on HO-1.


Optical probe for local void fraction and interface velocity measurements.
In view of the importance of obtaining unsteady local void fraction and interface velocities in liquid-vapor two-phase flows, an optical probe with a controlled tip geometry was developed and is described. In order to minimize the disturbances caused to the flow field by the presence of the probe, its dimensions have been miniaturized. The electronic and hydrodynamic responses of the probe were investigated experimentally. The probe was found to be sensitive to both the interface velocities and the phase present at the probe tip. A possible explanation for the behavior of the probe is presented. Within the velocity range checked and with proper calibration, the optical probe described can be used to determine both local void fractions and interface velocities.


Multinational corporations, the politics of the world economy, and their effects on women's health in the developing world: a review.
Presently, globalization and the world economy maintain power relations that hamper the economic integrity and the political autonomy of the developing world. My paper addresses specific economic conditions that perpetuate poverty and poor health. I examine multinational corporations and their effects on women's health, particularly in Mexico and parts of Asia. The advent of multinational corporate business in Mexico, Malaysia, Philippines, India, and Indonesia has led to increased poverty and human rights abuses. Women bear the brunt of this because of specific international economic arrangements and their low social status, both locally and globally. As a result, their physical, mental, and emotional health is suffering. Solutions to these health problems have been proposed on multiple levels: international top-down approaches (i.e., employing international protectionist regulatory standards, exposing multinationals who infringe on their workers' human rights), as well as local grassroots organizational campaigns (i.e., conducting informational human rights workshops for factory workers). Ultimately, the answers lie in holding corporations accountable to their laborers while developing countries maintain their comparative advantage; this is the only way women's health will improve and the developing world can entice corporate investment.


P2S5 Reactive Flux Method for the Rapid Synthesis of Mono- and Bimetallic 2D Thiophosphates M2-xM'xP2S6.
We report a reactive flux technique using the common reagent P2S5 and metal precursors developed to circumvent the synthetic bottleneck for producing high-quality single- and mixed-metal two-dimensional (2D) thiophosphate materials. For the monometallic compound, M2P2S6 (M = Ni, Fe, and Mn), phase-pure materials were quickly synthesized and annealed at 650 °C for 1 h. Crystals of dimensions of several millimeters were grown for some of the metal thiophosphates using optimized heating profiles. The homogeneity of the bimetallic thiophosphates MM'P2S6 (M, M' = Ni, Fe, and Mn) was elucidated using energy-dispersive X-ray spectroscopy and Rietveld refinement. The quality of the selected materials was characterized by transmission electron microscopy and atomic force microscopy measurements. We report two novel bimetallic thiophosphates, MnCoP2S6 and FeCoP2S6. The Ni2P2S6 and MnNiP2S6 flux reactions were monitored in situ using variable-temperature powder X-ray diffraction to understand the formation reaction pathways. The phases were directly formed in a single step at approximately 375 °C. The work functions of the semiconducting materials were determined and ranged from 5.28 to 5.72 eV.


Ultrasensitive Immunosensor Based on Langmuir-Blodgett Deposited Ordered Graphene Assemblies for Dengue Detection.
In this manuscript partially reduced graphene oxide (RGO) nanosheet-based electrodes have been utilized for quantification of the NS1 protein and subsequently for dengue detection. NS1 is the biomarker found circulating in the body of dengue-infected persons on or after first day of the appearance of disease symptoms. Graphene oxide (GO) has been synthesized using a modified Hummer's method, and its ordered nanostructured films have been electrophoretically deposited on indium tin oxide (ITO)-coated glass substrates using Langmuir-Blodgett (LB) deposition. Deposited LB films of GO have been reduced with hydrazine vapors to obtain RGO-coated ITO electrodes. NS1 antibodies have been grafted onto the ordered thin films using covalent linking, and the bioelectrodes have been utilized for the specific detection of NS1 antigen. The electrochemical performance of the fabricated bioelectrodes for NS1 antigen detection has been explored in standard and spiked sera samples. The limit of detection for the standard samples and spiked serum samples is found to be 0.069 ng mL-1 and 0.081 ng mL-1, respectively, with a sensitivity of 8.41 and 36.75 Ω per ng mL, respectively, in the detection range of 101 to 107 ng mL-1.


Enzymology of Fructan Synthesis in Grasses: Properties of Sucrose-Sucrose-Fructosyltransferase in Barley Leaves (Hordeum vulgare L. cv Gerbel).
Fructan synthesis was induced in excised primary leaf blades of Hordeum vulgare L. cv Gerbel by illumination in 30 millimolar fructose. This treatment induced a 26-fold increase of sucrose-sucrose-fructosyltransferase (SST, EC 126.96.36.199) activity within 24 hours. Acid invertase (EC 126.96.36.199) activity remained about constant. By preparing protoplasts from induced leaves, approximately 80% of the invertase activity was removed with the cell walls while SST was retained. The protoplast homogenate was used to partially purify and characterize SST. Acid precipitation (pH 4.75) and anion exchange chromatography (fast protein liquid chromatography on Mono ;Q') resulted in a recovery of about 80% of total SST activity. The principal activity (SST 1), accounting for 85% of the activity recovered, was purified about 200-fold. It was essentially free of invertase activity and catalyzed the synthesis of a trisaccharide which co-chromatographed with isokestose (1F-beta-fructosylsucrose). The remaining 15% of SST activity (SST 2) was purified about 35-fold. It retained substantial invertase activity and catalyzed the synthesis of only one trisaccharide which co-chromatographed with kestose (6F-beta-fructosylsucrose). It is concluded that barley leaves which store mainly fructan of the phlein type (beta-2-6 polyfructosylsucrose), nevertheless contain sucrose-sucrose 1F-beta-d-fructosyltransferase as the key enzyme of fructan synthesis.


Spatial averaging in the beam of a piston transducer.
This paper presents a theoretical analysis of the spatially averaged free-field responses of phase-sensitive and phase-insensitive receivers centered in the beam of a harmonically excited piston transmitter. The responses of unfocused circular plane piston receivers are analyzed, and both unfocused and spherically focused piston transmitters are considered. A set of closed-form expressions figures prominently in the analysis. The expressions are based on the Lommel diffraction formulation which is, in turn, based on the Fresnel approximation. Although approximate, the expressions allow for quick and easy estimation of phase-sensitive or phase-insensitive unfocused piston receiver responses. It is shown that the spatial averaging effects associated with phase-sensitive and phase-insensitive receivers are virtually identical when gamma < or = 0.1, where gamma = b/a is the ratio of receiver radius b to transmitter radius a. In addition, numerical results obtained from the closed-form expressions are compared with previously reported results. The comparisons indicate that the approximate results are valid from the m = 3 maxima forward under the assumption of linear propagation when ka > 58, where k is the circular wave number. Finally, it is pointed out that the closed-form expressions may prove useful in the estimation of the potential for bioeffects associated with diagnostic ultrasound.


Metastatic malignant melanoma affecting stomach.
Malignant melanoma has been reported to affect all organs of the human body with the metastasis. Stomach metastases are quite rare in cases of the most commonly reported primaries including, melanoma and breast, and lung carcinomas. This report involves, a 56-year-old man suffering from melanoma of the lower extremity that developed into gastric, pulmonary, and brain metastases. The patient who experienced epigastric pain with suspicious melanoma was referred to undergo endoscopy. A black and white ulcer with dimensions of 1 × 1.5 cm and a mass of 1 × 2 cm mass were found at D1 and lesser curvature. Physical examination revealed a 2 × 3 cm black lesion at his right heel. Pathologic examination provided multiple pieces of creamy soft-tissue measuring 0.3 × 0.2 × 0.1 cm showing pigmented tumor cells in lamina propria. Staining biopsy samples with anti-HMB-45 and Fontana demonstrated a higher degree of positivity in tumor cells. The patient was admitted to the hospital, but unfortunately his general conditions were deteriorated and he developed convulsion and deceased four days after admission.


Structure and complete nucleotide sequence of the gene encoding chicken cytosolic adenylate kinase.
The gene encoding cytosolic adenylate kinase (AK1) was isolated from a chicken genomic DNA library by using its cDNA as a hybridization probe. The chicken AK1 gene spanned about 6 kilobase pairs and consisted of 7 exons. Analyses of the 5'-flanking region sequence and S1 nuclease mapping revealed that the transcription initiation site is located at 84 base pairs upstream from the ATG initiation codon. The TATA box and the putative CAT box were located 29 base pairs and 97 base pairs upstream from the transcription initiation site, respectively. A total of 7 GC boxes were found in the 5'-flanking region, the exon 1, and the intron 1. The GC boxes were surrounded by the sequences with extremely high G+C contents. When projected on the three-dimensional structure of the AK1 protein molecule, introns fell either between or near the ends of alpha-helices and beta-strands, and most of the coding exons encoded at least one alpha-helix and one beta-strand. The dot matrix plot analysis between chicken AK1 and bovine mitochondrial adenylate kinase (AK2) suggested that the AK1 gene might have evolved from the AK2 gene by deletion of one or more exon(s).


Addressing the Protease Bias in Quantitative Proteomics.
Protein quantification strategies using multiple proteases have been shown to deliver poor interprotease accuracy in label-free mass spectrometry experiments. By utilizing six different proteases with different cleavage sites, this study explores the protease bias and its effect on accuracy and precision by using recombinant protein standards. We established 557 SRM assays, using a recombinant protein standard resource, toward 10 proteins in human plasma and determined their concentration with multiple proteases. The quantified peptides of these plasma proteins spanned 3 orders of magnitude (0.02-70 μM). In total, 60 peptides were used for absolute quantification and the majority of the peptides showed high robustness. The retained reproducibility was achieved by quantifying plasma proteins using spiked stable isotope standard recombinant proteins in a targeted proteomics workflow.


Field validation of hsp70 stress proteins as biomarkers in Asian clam (Potamocorbula amurensis): is downregulation an indicator of stress?
The focus of this paper is to consider the applicability of the hsp70 stress protein response as a biomarker in field studies. Stress proteins (or heat shock proteins, hsp) of the hsp70 family are induced by sublethal concentrations of a variety of environmental pollutants. However, few studies have applied these proteins as biomarkers of environmental stress under field conditions. Our laboratory is investigating hsp70 proteins and other responses of Asian clam (Potamocorbula amurensis) as potential biomarkers in laboratory and field studies. Our efforts include two studies presently being conducted in northern San Francisco Bay: (1) monthly collection of clams from four sites along a cadmium contamination gradient; (2) 7 day in situ exposure of clams at two selected sites at Mare Island Naval Shipyard. Here we present results on hsp70 proteins in P. amurensis in field-collected and outplanted clams. Both field projects are ongoing, therefore the results presented here do not represent completed studies; rather, they illustrate a portion of our experience. For this workshop, we illustrate weaknesses and strengths of these proteins as biomarkers, and we underscore where additional work is needed. In field-collected clams (study no. 1), site-specific differences in levels of two hsp70 proteins, hsp70 and hsp76, were measured in May and June 1997. Although an inverse correlation exists between cadmium tissue concentrations and hsp70 protein levels, differences detected may be reflective of a salinity gradient. Results from recent laboratory exposures to cadmium and a range of salinities are discussed. After in situ exposure for 7 days (study no. 2), both hsp70 and hsp76 levels were significantly reduced in clams from site R. However, given a brief heat-shock in the laboratory, hsp70 protein levels were significantly higher in clams from this site than in controls. Results indicate that downregulation as well as upregulation of hsp70 proteins may be indicators of stress in P. amurensis.


Cell shape regulates subcellular organelle location to control early Ca2+ signal dynamics in vascular smooth muscle cells.
The shape of the cell is connected to its function; however, we do not fully understand underlying mechanisms by which global shape regulates a cell's functional capabilities. Using theory, experiments and simulation, we investigated how physiologically relevant cell shape changes affect subcellular organization, and consequently intracellular signaling, to control information flow needed for phenotypic function. Vascular smooth muscle cells going from a proliferative and motile circular shape to a contractile fusiform shape show changes in the location of the sarcoplasmic reticulum, inter-organelle distances, and differential distribution of receptors in the plasma membrane. These factors together lead to the modulation of signals transduced by the M3 muscarinic receptor/Gq/PLCβ pathway at the plasma membrane, amplifying Ca2+ dynamics in the cytoplasm, and the nucleus resulting in phenotypic changes, as determined by increased activity of myosin light chain kinase in the cytoplasm and enhanced nuclear localization of the transcription factor NFAT. Taken together, our observations show a systems level phenomenon whereby global cell shape affects subcellular organization to modulate signaling that enables phenotypic changes.


Effects of [(pF)Phe(4)]nociceptin/orphanin FQ-(1-13)NH(2) on GTPgamma(35)S binding and cAMP formation in Chinese hamster ovary cells expressing the human nociceptin/orphanin FQ receptor.
Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ receptor (NOP). In this study using Chinese hamster ovary (CHO) cells expressing the human NOP (CHO(hNOP)) and GTPgamma(35)S binding and cAMP inhibition assays, we have characterised a novel N/OFQ ligand, [(pF)Phe(4)]N/OFQ-(1-13)NH(2), ([(pF)Phe(4)]). [(pF)Phe(4)] was produced by insertion of a fluorine atom into the para position of the phenyl ring of Phe(4) of the truncated N/OFQ peptide N/OFQ-(1-13)NH(2). In CHO(hNOP) membranes [(pF)Phe(4)] and N/OFQ-(1-13)NH(2) stimulated GTPgamma35S binding with pEC(50) (mean+/-S.E.M.) values of 9.55+/-0.01 and 8.94+/-0.5 (P<0.05), respectively. In whole CHO(hNOP) cells [(pF)Phe(4)] and N/OFQ-(1-13)NH(2) inhibited forskolin stimulated cAMP formation with pEC(50) values of 10.19+/-0.06 and 9.60+/-0.04, respectively (P<0.05). [(pF)Phe(4)] was more potent ( approximately 4 fold) than N/OFQ-(1-13)NH(2). In both assays, the effects of [(pF)Phe(4)] and N/OFQ-(1-13)NH(2) were pertussis toxin sensitive and reversed by the NOP antagonists J-113397 (pA(2)/pK(B) values 7.89-8.53) and III-BTD (pA(2)/pK(B) values 7.27-7.96). [(pF)Phe(4)] is therefore a potent full agonist at NOP receptors that will be useful as pharmacological tool for defining the role of N/OFQ-NOP system in health and disease.


CA-125 serum level in the diagnosis of pelvic masses: comparison with other methods.
The Authors have evaluated the diagnostic contribution offered by the serum dosage of the antigen CA-125 in the diagnostics of pelvic masses. This method has been compared with the objective and echographic evaluation, as a noninvasive method of enquiry in the diagnosis of malignant neoplasias of the ovary. The Authors endorse the increase in diagnostic sensitivity brought about by the evaluation of this marker, above all if it is inserted into an integrated diagnosis.


Amino acid residues essential for function of the MexF efflux pump protein of Pseudomonas aeruginosa.
At least four broad-spectrum efflux pumps (Mex) are involved in elevated intrinsic antibiotic resistance as well as in acquired multidrug resistance in Pseudomonas aeruginosa. Substrate specificity of the Mex pumps has been shown to be determined by the cytoplasmic membrane component (MexB, MexD, MexF, and MexY) of the tripartite efflux pump system. Alignment of their amino acid sequences with those of the homologous AcrB and AcrD pump proteins of Escherichia coli showed conservation of five charged amino acid residues located in or next to transmembrane segments (TMS). These residues were mutated in the MexF gene by site-directed mutagenesis and replaced by residues of opposite or neutral charge. MexF proteins containing combined D410A and A411G substitutions located in TMS4 were completely inactive. Similarly, the substitutions E417K (next to TMS4) and K951E (TMS10) also caused loss of activity towards all tested antibiotics. The substitution E349K in TMS2 resulted in a MexF mutant protein which was unable to transport trimethoprim and quinolones but retained partial activity for the transport of chloramphenicol. All mutated MexF proteins were expressed at comparable levels when tested by Western blot analysis. It is concluded that charged residues located in or close to TMS are essential for proper function of MexF.


Strain-specific differences in the vermian granular layer of albino rats.
Foliation of the cerebella of Sprague-Dawley rats (strain Han:SPRD) is more advanced than in Wistar rats (strain Chbb:THOM). The differences expressed as length of the granular layer in median sections were significant in lobules VIa, VIII, IX and X. The length of the other vermian lobules is generally higher in the former strain. With regard to the volume of the granular layer, the situation is reversed, indicating that the lateral extent and thickness of vermian lobules in Wistar rats (strain Chbb:THOM) is generally larger. These quantitative differences may express differences in cerebellar microcircuitry and fibre connections in the cortex of Wistar and Sprague-Dawley rats.


Glycosylation Profile of IgG in Moderate Kidney Dysfunction.
Glycans constitute the most abundant and diverse form of the post-translational modifications, and animal studies have suggested the involvement of IgG glycosylation in mechanisms of renal damage. Here, we explored the associations between IgG glycans and renal function in 3274 individuals from the TwinsUK registry. We analyzed the correlation between renal function measured as eGFR and 76 N-glycan traits using linear regressions adjusted for covariates and multiple testing in the larger population. We replicated our results in 31 monozygotic twin pairs discordant for renal function. Results from both analyses were then meta-analyzed. Fourteen glycan traits were associated with renal function in the discovery sample (P<6.5×10(-4)) and remained significant after validation. Those glycan traits belong to three main glycosylation features: galactosylation, sialylation, and level of bisecting N-acetylglucosamine of the IgG glycans. These results show the role of IgG glycosylation in kidney function and provide novel insight into the pathophysiology of CKD and potential diagnostic and therapeutic targets.


Paediatric dentistry: Fauchard and before.
Although conventional wisdom suggests that paediatric dentistry was not practised until the early twentieth century it was in fact recorded in much earlier times. The authors detail many authors and books from previous centuries concerned with weaning, infant feeding, remedies for teething pains and eruption. Further details include the early advice on the avoidance of caries and the beginnings of the specialty of orthodontics.


Integrated positron-emission tomography for nodal staging in lung cancer.
As lymph node metastasis is the most important factor determining the surgical outcome of lung cancer, we evaluated the accuracy and clinical usefulness of functional imaging with integrated positron-emission tomography and computed tomography in nodal staging of non-small-cell lung cancer. Between October 2003 and August 2004, 43 newly diagnosed patients underwent curative surgical resection or mediastinoscopic nodal biopsy after chest computed tomography as well as whole-body functional imaging for clinical staging. Based on histopathologic findings in the lymph nodes, we compared the diagnostic usefulness of computed tomography and functional imaging. Twenty-two patients were N0 stage, 6 were N1, 11 were N2, and 4 were N3. Although functional imaging seemed to be superior for evaluation of N2 nodes, there were no significant differences in the sensitivity, specificity, positive-predictive value, negative-predictive value, or accuracy. The situation was similar for N1 nodes, and there were no significant differences except for the false-negative rate. High false-positive and negative-rates for N2 lymph nodes suggest that functional imaging should not replace mediastinoscopy.


Sedation in outpatient oral surgery. Comparison of temazepam by mouth and diazepam i.v.
In a randomized double-blind, parallel groups study, 39 patients undergoing surgical removal of impacted third molar teeth received either temazepam 40 mg by mouth (as soft gelatin capsules) followed at 35 min by i.v. saline, or oral placebo followed at 35 min by i.v. diazepam 10 mg (Diazemuls). Rapid onset of significant anxiolytic activity and psychomotor depression was seen following temazepam, while the pattern and duration of postoperative sedation measured with standard psychometric tests, were similar for both treatments. Ratings by the surgeon and by the patients indicated that sedation following the two treatments was comparable. No significant cardiovascular complications were found with either treatment. The findings indicate that rapidly acting oral benzodiazepines such as temazepam provide safe, effective alternatives to i.v. diazepam for sedation in outpatients undergoing minor surgical procedures.


A CYC-RAD-DIV-DRIF interaction likely pre-dates the origin of floral monosymmetry in Lamiales.
An outstanding question in evolutionary biology is how genetic interactions defining novel traits evolve. They may evolve either by de novo assembly of previously non-interacting genes or by en bloc co-option of interactions from other functions. We tested these hypotheses in the context of a novel phenotype-Lamiales flower monosymmetry-defined by a developmental program that relies on regulatory interaction among CYCLOIDEA, RADIALIS, DIVARICATA, and DRIF gene products. In Antirrhinum majus (snapdragon), representing Lamiales, we tested whether components of this program likely function beyond their previously known role in petal and stamen development. In Solanum lycopersicum (tomato), representing Solanales which diverged from Lamiales before the origin of Lamiales floral monosymmetry, we additionally tested for regulatory interactions in this program. We found that RADIALIS, DIVARICATA, and DRIF are expressed in snapdragon ovaries and developing fruit, similar to their homologs during tomato fruit development. In addition, we found that a tomato CYCLOIDEA ortholog positively regulates a tomato RADIALIS ortholog. Our results provide preliminary support to the hypothesis that the developmental program defining floral monosymmetry in Lamiales was co-opted en bloc from a function in carpel development. This expands our understanding of novel trait evolution facilitated by co-option of existing regulatory interactions.


Sleep, memory, and plasticity.
Although the functions of sleep remain largely unknown, one of the most exciting hypotheses is that sleep contributes importantly to processes of memory and brain plasticity. Over the past decade, a large body of work, spanning most of the neurosciences, has provided a substantive body of evidence supporting this role of sleep in what is becoming known as sleep-dependent memory processing. We review these findings, focusing specifically on the role of sleep in (a) memory encoding, (b) memory consolidation, (c) brain plasticity, and (d) memory reconsolidation; we finish with a summary of the field and its potential future directions.


The interaction between lining materials and composite resin restorative materials.
The effects of four lining materials, Dycal, Procal, Cavitec and Poly F cement on Adaptic and Concise have been investigated in vitro. The parameters studied were surface roughness, hardness and colour both with and without an intermediate (or bonding) resin being present between the restorative material and the liner. The effects of the four liners on the composites varied both between the lining materials themselves and with the composite resin. Two materials, Procal and Dycal, had little interaction with the composites, provided an intermediate resin was used with the latter. Cavitec appeared to have an adverse reaction with the composites and Poly F, whilst having no effect on the colour of the composites, did increase surface roughness. The adverse effects of linig materials were ascribed to minor constituents, particularly methyl salicylate, present in the formulation.