Impact of GLI-2012 Spirometric References and Lower Limit of Normal on Prevalence of COPD in Older Urban Thai Persons.
Previous analysis of survey data from a study in older urban Thai persons reported prevalence of chronic obstructive pulmonary disease (COPD) of 7.11% according to formerly recommended criteria that used fixed ratio (70%) of pre-bronchodilator FEV1/FVC as the cut-off value. In 2012, the Global Lung Initiative (GLI)-2012 equations for spirometric reference were established and the diagnostic criteria for COPD were changed. To reanalyze the data collected during the 2002 respiratory health survey to determine prevalence of COPD in older urban Thai persons according to the new GLI-2012 equations. Demographic and clinical data of 3,094 subjects aged ≥ 60 years from 124 urban communities were re-analyzed. Prevalence of COPD determined by post-bronchodilator FEV1/FVC and GLI-2012 equations using lower limit of normal by the Lambda-Mu-Sigma method (LMS-LLN) was compared to COPD prevalence findings based on criteria used in previous analysis. Prevalence of COPD in the study population using post-bronchodilator FEV1/FVC and LMS-LLN was 6.50% (95% CI: 5.63-7.3 7), compared with 7.82% (95% CI: 6.87-8.77) when fixed ratio (70%) of FEV1/FVC was used as cut-off. Diagnostic agreement of COPD between LMS-LLN and fixed ratio was high (kappa 0.88, p < 0.0001). However 45/242 (18.6%) subjects diagnosed as COPD by fixed ratio criteria were considered as "over-diagnosed" when LMS-LLN was used as the standard cut-off The same comparison applied to subjects aged 80 years revealed an increased rate of over-diagnosis to 7/22 (31.8%) subjects. Higher agreement was observed (kappa 0.95, p < 0.0001) when comparing between cut-offs for diagnosis of "at least GOLD stage II" COPD. Prevalence of COPD in older urban Thai persons was lower when LMS-LLN was substituted for fixed ratio (70%) of FEV1/FVC. Agreement in COPD diagnosis between both criteria was high, but a substantial proportion of subjects may be over-diagnosed


Effects of orthographic and phonological word length on memory for lists shown at RSVP and STM rates.
This article reports 3 experiments in which effects of orthographic and phonological word length on memory were examined for short lists shown at rapid serial visual presentation (RSVP) and short-term memory (STM) rates. Only visual-orthographic length reduced RSVP serial recall, whereas both orthographic and phonological length lowered recall for STM lists in Experiment 1. Word-length effects may arise from output processes or from the temporal duration of output in recall. In 2 further experiments, output demands were reduced through the use of a recognition test. Recognition accuracy was impaired only by orthographic length for RSVP lists and by phonological length for STM lists in both experiments. The results demonstrate 2 item length effects not simply attributable to increased output time in recall, and implications for theories of STM are considered.


Genetic manipulation of stromal cell-derived factor-1 attests the pivotal role of the autocrine SDF-1-CXCR4 pathway in the aggressiveness of breast cancer cells.
Stromal cell-derived factor-1 (SDF-1), via its receptor CXCR4, has been implicated in metastasis of cancer, including breast cancer. Exogenous SDF-1 is known to regulate locomotion, chemotaxis and adhesion. The knowledge regarding the effect of autocrine SDF-1 on breast cancer cells is not available. The current study evaluated the effects of SDF-1 on the biological behaviour of breast cancer cells by genetically modifying the expression of SDF-1 in breast cancer cells. Two human breast cancer cell lines (MDA-MB-231 and MDA-MB-435s) and a human fetal lung fibroblast cell line (MRC5) were used. The expression of SDF-1 and the SDF-1 receptor, CXCR4 in the cell lines were studied. Expression cassettes of human SDF-1 and hammerhead ribozyme transgenes specifically targeting human SDF-1 were constructed and used to over-express SDF-1 or to knockout the expression of SDF-1 in cancer cells, respectively. Invasiveness, migration and growth of the genetically modified cells were assessed. SDF-1 was expressed in wild-type human breast cancer cell line MDA-MB-435s and fibroblast cell line MRC5, but not in MDA-MB-231 cell line. In contrast, CXCR4 expression was observed in all three cell lines tested. The ability of invasion and migration was significantly reduced in SDF-1 knockout MDA-MB-435s cells, compared with wild-type and vector control cells (p<0.01). On the other hand, SDF-1 transfected MDA-MB-231epsilonSDF1+/+ cells that stably expressed SDF-1 showed a different behaviour from MDA-MB-231SDF1+/- (plasmid control) and wild-type MDA-MB-231 cells, both being SDF-1 negative. MDA-MB-231epsilonSDF1+/+ cells displayed a higher degree of invasiveness and migration, compared with wild-type and MDA-MB-231SDF+/- cells (p<0.01). Furthermore, SDF1-knockout MDA-MB-435s cells showed a slower growth rate over a 7-day period compared with the respective control and wild-type MDA-MB-435s cells. In contrast, the growth of the SDF-1 transfected MDA-MB-231SDF1+/+ cells was markedly enhanced when compared with wild-type and vector control cells. Breast cancer cell lines, when equipped with the autocrine SDF-1-CXCR4 signal pathway, display aggressive behaviour, including an increase in invasiveness, migration together with faster growth. SDF-1, together with its receptor CXCR4 may provide important information for predicting the aggressive nature and constitute important therapeutic targets in human breast cancer.


Isolation and characterization of mutants of the Bacillus subtilis oligopeptide permease with altered specificity of oligopeptide transport.
Bacterial oligopeptide permeases are members of the large family of ATP binding cassette transporters and typically import peptides of 3 to 5 amino acids, apparently independently of sequence. Oligopeptide permeases are needed for bacteria to utilize peptides as nutrient sources and are sometimes involved in signal transduction pathways. The Bacillus subtilis oligopeptide permease stimulates competence development and the initiation of sporulation, at least in part, by importing specific signaling peptides. We isolated rare, partly functional mutations in B. subtilis opp. The mutants were resistant to a toxic tripeptide but still retained the ability to sporulate and/or become competent. The mutations, mostly in the oligopeptide binding protein located on the cell surface, affected residues whose alteration appears to change the specificity of oligopeptide transport.


A Pilot Study of the Effect of Outsole Hardness on Lower Limb Kinematics and Kinetics during Soccer Related Movements.
The purpose of this study was to investigate the effect of different outsole hardness of turf cleats shoes on the lower limb kinematics and kinetics of soccer players playing on artificial turf. The participants were required to complete tasks of straight running and 45° left sidestep cutting movements, respectively, at the speed of 4.5 ± 0.2 m/s on artificial turf. They were asked to randomly select turf cleats shoes with a soft outsole (SO), medium hardness outsole (MO) and hard outsole (HO). During the stance phase of straight running, peak pressure and force-time integral in medial forefoot (MFF) of players wearing cleats shoes with MO were significantly higher than those wearing cleats shoes with SO. During the stance phase of a 45° cutting maneuver, players wearing cleats shoes with SO showed significantly higher peak knee flexion and abduction angles than the HO group. Players wearing cleats shoes with SO also showed higher ankle dorsiflexion and inversion angles compared with those wearing cleats shoes with HO. The vertical average loading rate (VALR) as well as peak pressure and force-time integral in the heel (H) and lateral forefoot (LFF) regions of players wearing cleats shoes with HO were significantly higher than those wearing shoes with SO. On the contrary, peak pressure and force-time integral of players wearing shoes with SO were significantly higher than those wearing shoes with HO in MFF. A higher vertical loading rate and plantar pressure of some areas may increase the potential risk of metatarsal stress fractures and plantar fasciitis. Therefore, this finding about turf cleats shoes could give some theoretic support for the design of turf cleats shoes and material optimization in the future.


Milestones in beef cattle genetic evaluation.
National beef cattle genetic evaluation programs have evolved in the United States over the last 35 yr to create important tools that are part of sustainable breeding programs. The history of national beef cattle genetic evaluation programs has lessons to offer the next generation of researchers as new approaches in molecular genetics and decision support are developed. Through a series of complex and intricate pressures from technology and organizational challenges, national cattle evaluation programs continue to grow in importance and impact. Development of enabling technologies and the interface of the disciplines of computer science, numerical methods, statistics, and quantitative genetics have created an example of how academics, government, and industry can work together to create more effective solutions to technical problems. The advent of mixed model procedures was complemented by a series of breakthrough discoveries that made what was previously considered intractable a reality. The creation of modern genetic evaluation procedures has followed a path characterized by a steady and constant approach to identification and solution for each technical problem encountered. At its core, the driving force for the evolution has been the need to constantly improve the accuracy of the predictions of genetic merit for breeding stock, especially young animals. Sensible approaches, such as the principle of economically relevant traits, were developed that created the rules to be followed as the programs grew. However, the current systems are far from complete or perfect. Modern genetic evaluation programs have a long way to go, and a great deal of improvement in the accuracy of prediction is still possible. But the greatest challenge remains: the need to understand that genetic predictions are only parameters for decision support procedures and not an end in themselves.


Glutathione reductase and nitroblue tetrazolium reduction deficiencies in neutrophils of patients with primary idiopathic myelofibrosis.
Latex ingestion and nitroblue tetrazolium reduction were measured in neutrophils of 40 patients with primary idiopathic myelofibrosis. The percentage of neutrophils that ingested latex, in the presence of either autologous or control sera, was lower (P less than 0.001) than that of the controls. The percentage of the ingesting neutrophils that reduced nitroblue tetrazolium was also lower (P less than 0.001) in the patients than in the controls. Activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione peroxidase and NAD(P)H oxidases were not different from those of the controls. In contrast, glutathione reductase activity was significantly lower (P less than 0.001) in the patients than in the controls either with or without the addition of flavin adenine dinucleotide. Glutathione reductase and nitroblue tetrazolium reduction activities were correlated (r = 0.913). These results are discussed within the framework of the acquired enzymopathies and the increased susceptibility to infection observed in these patients.


Psychometric analysis of the Broome Pelvic Muscle Self-Efficacy Scale in African-American women with incontinence.
There is a paucity of research on African-American women and incontinence. Previous research has demonstrated that pelvic muscle exercises can reduce or eliminate incontinence in women. This methodological study reports findings about incontinence, self-efficacy, depression, and quality of life in African-American women with incontinence. This study further reports the psychometric analysis of the Broome Pelvic Muscle Self-Efficacy Scale in this population.


Experiential Learning for Psychomotor Skills Development of Emergency Medical Services (EMS) Students: An Action Research.
Experiential learning is useful for fostering the development of a wide range of clinical and practical skills. This study aimed to determine the usefulness of experiential learning for psychomotor skills development of emergency medical services (EMS) students. An action research approach was used because it is useful for linking theory with action and practice. The Field Internship Student Data Acquisition Project (FISDAP) tool was used to assess and monitor students' performance and competencies achievement in psychomotor skills. The study was conducted at Prince Sultan College for Emergency Medical Services (PSCEMS), King Saud University (KSU). Skills performance of 71 EMS students were analysed in the experiential learning implemented throughout the curriculum over 3 years. The finding indicates that the students' skills performance falls below the minimum requirement during the clinical practicum and significantly improves during the time of internship period. The overall success rate ranges between 26.58% and 35.74% across all the psychomotor skills, whereas during the internship year student's success rate ranges between 85.49% and 99.4% across all the psychomotor skills. The findings of this study are promising and show that experiential learning is a useful and effective way to develop psychomotor skills and competencies in EMS students. Educators and policymakers can use the findings for strategizing policies for curriculum planning and development.


The cost effectiveness of orlistat in a 1-year weight-management programme for treating overweight and obese patients in Sweden : a treatment responder approach.
To calculate the cost effectiveness (from the Swedish healthcare perspective) of orlistat plus diet for an obese and overweight population in a 1-year weight-management responder programme versus a 1-year weight-management programme based on diet only. As a reference, orlistat plus diet and diet only were also compared with a no-diet alternative. Costs and effectiveness were calculated in a decision-tree model by means of Monte Carlo simulation. Efficacy was derived from a pooled analysis of the orlistat clinical trial programme. Acquisition costs for orlistat (euro, 2003 prices), healthcare costs for visits to doctors and dieticians related to weight management, and costs related to the difference in diabetes mellitus incidence between treatment arms were included in the analysis. The health benefit of temporary weight loss was measured in the number of quality-adjusted life-years (QALYs) gained. The number of responding (those with >5% weight loss) patients at month 3 was almost twice as high with orlistat compared with diet only: 48.9% versus 26.3%. Responding orlistat patients had a weight loss of 15.5% at month 12 compared with 7.9% for all patients on diet only. The incremental cost-effectiveness ratio (ICER) per QALY gained versus diet only was estimated to be 13,125 euro for the average patient starting on orlistat. When orlistat was compared with no diet, the cost effectiveness was improved. However, comparing diet only with no diet gave a slightly higher ICER, indicating that orlistat had an extended dominance over the diet-only alternative. Our estimates indicated that orlistat in a 12-month dietary responder programme increased the number of QALYs and reduced the cumulative incidence of diabetes compared with diet only. Patients starting on orlistat in addition to a dietary programme achieved an ICER that was similar to many other well accepted healthcare treatment programmes. In order to improve the precision of our calculations, we need to confirm the key assumptions regarding temporary weight loss and utility gains, and the relationship between temporary weight loss and diabetes, as well as other co-morbidities, and to have better knowledge of the long-term impact of weight-management programmes in clinical practice, such as changes in weight-controlling behaviours and sustainability of weight loss.


Domain architecture and activity of human Pex19p, a chaperone-like protein for intracellular trafficking of peroxisomal membrane proteins.
Pex19p is a peroxin involved in peroxisomal membrane biogenesis and probably functions as a chaperone and/or soluble receptor specific for cargo peroxisomal membrane proteins (PMPs). To elucidate the functional constituents of Pex19p in terms of the protein structure, we investigated its domain architecture and binding affinity toward various PMPs and peroxins. The human Pex19p cDNA was overexpressed in Escherichia coli, and a highly purified sample of the Pex19p protein was prepared. When PMP22 was synthesized by cell-free translation in the presence of Pex19p, the PMP22 bound to Pex19p was soluble, whereas PMP22 alone was insoluble. This observation shows that Pex19p plays a role in capturing PMP and maintaining its solubility. In a similar manner, Pex19p was bound to PMP70 and Pex16p as well as the Pex3p soluble fragment. Limited proteolysis analyses revealed that Pex19p consists of the C-terminal core domain flanking the flexible N-terminal region. Separation of Pex19p into its N- and C-terminal halves abolished interactions with PMP22, PMP70, and Pex16p. In contrast, the flexible N-terminal half of Pex19p was bound to the Pex3p soluble fragment, suggesting that the binding mode of Pex3p toward Pex19p differs from that of other PMPs. This idea is supported by our detection of the Pex19p-Pex3p-PMP22 ternary complex.


Cardiovascular effects of total intravenous anesthesia using ketamine-medetomidine-propofol (KMP-TIVA) in horses undergoing surgery.
Cardiovascular effects of total intravenous anesthesia using ketamine-medetomidine-propofol drug combination (KMP-TIVA) were determined in 5 Thoroughbred horses undergoing surgery. The horses were anesthetized with intravenous administration (IV) of ketamine (2.5 mg/kg) and midazolam (0.04 mg/kg) following premedication with medetomidne (5 µg/kg, IV) and artificially ventilated. Surgical anesthesia was maintained by controlling propofol infusion rate (initially 0.20 mg/kg/min following an IV loading dose of 0.5 mg/kg) and constant rate infusions of ketamine (1 mg/kg/hr) and medetomidine (1.25 µg/kg/hr). The horses were anesthetized for 175 ± 14 min (range from 160 to 197 min). Propofol infusion rates ranged from 0.13 to 0.17 mg/kg/min, and plasma concentration (Cpl) of propofol ranged from 11.4 to 13.3 µg/ml during surgery. Cardiovascular measurements during surgery remained within clinically acceptable ranges in the horses (heart rate: 33 to 37 beats/min, mean arterial blood pressure: 111 to 119 mmHg, cardiac index: 48 to 53 ml/kg/min, stroke volume: 650 to 800 ml/beat and systemic vascular resistance: 311 to 398 dynes/sec/cm(5)). The propofol Cpl declined rapidly after the cessation of propofol infusion and was significantly lower at 10 min (4.5 ± 1.5 µg/ml), extubation (4.0 ± 1.2 µg/ml) and standing (2.4 ± 0.9 µg/ml) compared with the Cpl at the end of propofol administration (11.4 ± 2.7 µg/ml). All the horses recovered uneventfully and stood at 74 ± 28 min after the cessation of anesthesia. KMP-TIVA provided satisfactory quality and control of anesthesia with minimum cardiovascular depression in horses undergoing surgery.


Protein structure validation and refinement using amide proton chemical shifts derived from quantum mechanics.
We present the ProCS method for the rapid and accurate prediction of protein backbone amide proton chemical shifts--sensitive probes of the geometry of key hydrogen bonds that determine protein structure. ProCS is parameterized against quantum mechanical (QM) calculations and reproduces high level QM results obtained for a small protein with an RMSD of 0.25 ppm (r = 0.94). ProCS is interfaced with the PHAISTOS protein simulation program and is used to infer statistical protein ensembles that reflect experimentally measured amide proton chemical shift values. Such chemical shift-based structural refinements, starting from high-resolution X-ray structures of Protein G, ubiquitin, and SMN Tudor Domain, result in average chemical shifts, hydrogen bond geometries, and trans-hydrogen bond ((h3)J(NC')) spin-spin coupling constants that are in excellent agreement with experiment. We show that the structural sensitivity of the QM-based amide proton chemical shift predictions is needed to obtain this agreement. The ProCS method thus offers a powerful new tool for refining the structures of hydrogen bonding networks to high accuracy with many potential applications such as protein flexibility in ligand binding.


Changing caring behaviours in rehabilitation after a hip fracture - A tool for empowerment?
Different rehabilitation programs after surgery have been presented to improve the outcome for patients with a hip fracture. Empowerment has been suggested as useful, but requires a change in the caring behaviours of health professionals. The aim with this study was to evaluate if training and supervision of the nursing staff could alter caring behaviours. A case-control study of nursing staff treating hip fracture patients was performed at a hospital with two sites. Training and supervision was given to the nursing staff at the intervention site. The intervention focused on creating positive care interaction by using eight guidelines. The evaluation was performed with recordings of a constructed caring situation before training, and observations of care situations at the ward before and after intervention. The results showed no differences at baseline between the two sites in the caring behaviours. After intervention, significant effects of caring behaviours were seen in seven out of eight guidelines, the effect sizes ranged from medium to large. The findings indicate that the nursing staff can change caring behaviours and facilitate the empowerment of patients with a hip fracture.


Prevention of canine leishmaniosis in a hyper-endemic area using a combination of 10% imidacloprid/4.5% flumethrin.
Dogs are the main reservoir hosts of Leishmania infantum, the agent of human zoonotic visceral leishmaniosis. This study investigated the efficacy of a polymer matrix collar containing a combination of 10% imidacloprid and 4.5% flumethrin as a novel prophylactic measure to prevent L. infantum infections in young dogs from a hyper-endemic area of southern Italy, with a view towards enhancing current control strategies against both human and canine leishmaniosis. The study was carried out on 124 young dogs, of which 63 were collared (Group A) while 61 were left untreated (Group B), from March-April 2011 until March 2012. Blood and skin samples were collected at baseline (April 2011) and at the first, second, third and fourth follow-up time points (July, September 2011 and November 2011, and March 2012, respectively). Bone marrow and conjunctiva were sampled at baseline and at the fourth follow-up. Serological, cytological and molecular tests were performed to detect the presence of L. infantum in the different tissues collected. At the end of the trial, no dog from Group A proved positive for L. infantum at any follow-up, whereas 22 dogs from Group B were infected (incidence density rate = 45.1%); therefore, the combination of 10% imidacloprid and 4.5% flumethrin was 100% efficacious for the prevention of L. infantum infection in young dogs prior to their first exposure to the parasite in a hyper-endemic area for CanL. The use of collars containing 10% imidacloprid and 4.5% flumethrin conferred long-term protection against infection by L. infantum to dogs located in a hyper-endemic area, thus representing a reliable and sustainable strategy to decrease the frequency and spread of this disease among the canine population which will ultimately result in the reduction of associated risks to human health.


In Vivo Hypolipidemic, Hypoglycemic, Antihyperglycemic, and In Vitro Antioxidant Effects of Podocarpus gracilis Leaf Extract and Fractions in Diabetic Mice.
Podocarpus gracilis is an evergreen, dioecious tree found in Ethiopia and other African nations. It can reach a height of 60 meters. Without any scientific validation, ethnobotanical studies conducted in Ethiopia revealed that the Podocarpus gracilis plant's leaf is consumed orally to treat diabetes mellitus. Hence, this study aims to evaluate the in vivo blood glucose level lowering, lipid-lowering, and in vitro-free radical scavenging responses of Podocarpus gracilis leaf extract and fractions on experimental mice induced with diabetes. The in vitro antioxidant activity of PGC (Podocarpus gracilis) leaf extract was assessed by using a diphenyl-2-picrylhydrazyl (DPPH) assay. The oral glucose-loaded, normoglycemic, and streptozotocin- (STZ-) induced diabetic mouse models were employed. In the STZ-induced mice model, the leaf extract and solvent fractions activity on serum lipid and weight were also measured. The extract and fractions were tested at 100, 200, and 400 mg/kg dosages. One-way ANOVA was used to determine the statistical significance of BGL (blood glucose level) changes within and between groups, and Tukey's post hoc multiple comparisons were then performed. In the acute toxicity study of Podocarpus gracilis leaf extract and fractions, there was no evidence of animal mortality at the maximum dose of 2 g/kg during the observation period. The extract-treated group with normoglycemia revealed a significant lowering in BGL at the 4-hour mark of 27.4% (p < 0.001) and 25.2% (p < 0.01) at doses of 200 mg/kg and 400 mg/kg, respectively, compared to that in negative control. In the oral glucose tolerance test (OGTT) model, only 400 mg/kg treated groups at 120 min after exposure showed a BGL reduction of 31.17% which was statistically significant (p < 0.05) in comparison to the negative control. In the single-dose STZ-induced model, eighth-hour BGL measurements from CE 100, CE 200, CE 400, and GLC5 showed drops in BGL of 43.1%, 44.1%, 45%, and 47.3% from baseline fasting BGL values. In the repeated streptozotocin (STZ)-induced model, at all doses of leaf extract and fractions, the fasting BGL was significantly (p < 0.001) reduced. Moreover, the leaf extract and solvent fractions have shown a significant (p < 0.001) reduction of serum lipids such as LDL, TC, and VLDL, and at the same time, it increases HDL at 14 days with body weight gained. In the test for antioxidant activity, the half-maximal inhibitory concentrations (IC50) for leaf extract and the standard medication (ascorbic acid) were 8.2 μg/ml and 3.3 μg/ml, respectively. The IC50 value denotes the concentration of the sample required to scavenge 50% DPPH radicals. The 80% hydromethanolic leaf extract and fractions of Podocarpus gracilis exhibited blood glucose lowering, lipid-lowering activity in normoglycemic, oral glucose tolerance test (OGTT) mode, and STZ-induced diabetic mice with weight gains. There is scientific support for the alleged traditional use as an antidiabetic, lipid-lowering, and antioxidant activity. The results need to be confirmed by future studies.


Aprotinin-Drug against Respiratory Diseases.
Aprotinin (APR) was discovered in 1930. APR is an effective pan-protease inhibitor, a typical "magic shotgun". Until 2007, APR was widely used as an antithrombotic and anti-inflammatory drug in cardiac and noncardiac surgeries for reduction of bleeding and thus limiting the need for blood transfusion. The ability of APR to inhibit proteolytic activation of some viruses leads to its use as an antiviral drug for the prevention and treatment of acute respiratory virus infections. However, due to incompetent interpretation of several clinical trials followed by incredible controversy in the literature, the usage of APR was nearly stopped for a decade worldwide. In 2015-2020, after re-analysis of these clinical trials' data the restrictions in APR usage were lifted worldwide. This review discusses antiviral mechanisms of APR action and summarizes current knowledge and prospective regarding the use of APR treatment for diseases caused by RNA-containing viruses, including influenza and SARS-CoV-2 viruses, or as a part of combination antiviral treatment.


Stimulation of calbindin-D9K (CaBP9K) gene expression by calcium and 1,25-dihydroxycholecalciferol in fetal rat duodenal organ culture.
We have used organ cultures of 18-day fetal rat duodena to study the regulation of calbindin-D9K (CaBP9K) gene expression by 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and calcium. The epithelium of the fetal rat duodena maintained in culture for 10 days in a defined serum-free medium with no exogenous 1,25(OH)2D3 contains differentiated enterocytes. Treatment with 10(-8) M 1,25(OH)2D3 resulted in a 2-fold increase in CaBP9K messenger RNA (mRNA) after 1 h; CaBP9K content was increased 2.5-fold in 24 h. Simultaneous treatment of cultures with 1,25(OH)2D3 and 1 microM actinomycin D selectively blocked 1,25(OH)2D3-stimulated CaBP9K mRNA and protein synthesis. Fifty micromolars of cycloheximide significantly decreased CaBP9K protein accumulation but not mRNA. These findings indicate that 1,25(OH)2D3 controls CaBP9K gene transcription. Enterocytes exhibit some CaBP9K gene expression after 10 days under basal culture conditions, suggesting that CaBP9K synthesis is not dependent on 1,25(OH)2D3 alone. This basal expression drops after 24 h in a calcium free medium with 1 mM EGTA, suggesting that extracellular calcium is involved in the control of this gene. Increasing the calcium concentration to 1.2 mM resulted in a 6-fold increase in CaBP9K mRNA after 3 h and a 10-fold increase in CaBP9K protein content after 24 h. Calcium may increase CaBP9K gene transcription, since simultaneous addition of 1 microM actinomycin D and calcium blocked the calcium effect on CaBP9K mRNA. Therefore, this in vitro study demonstrates that both calcium and 1,25(OH)2D3 stimulate CaBP9K gene expression in the rat duodenum.


Southern Peru desert shattered by the great 2001 earthquake: implications for paleoseismic and paleo-El Nino-Southern Oscillation records.
In the desert region around the coastal city of Ilo, the great southern Peru earthquake of June 23, 2001 (8.2-8.4 moment magnitude), produced intense and widespread ground-failure effects. These effects included abundant landslides, pervasive ground cracking, microfracturing of surficial hillslope materials, collapse of drainage banks over long stretches, widening of hillside rills, and lengthening of first-order tributary channels. We have coined the term "shattered landscape" to describe the severity of these effects. Long-term consequences of this landscape shattering are inferred to include increased runoff and sediment transport during postearthquake rainstorms. This inference was confirmed during the first minor postearthquake rainstorm there, which occurred in June and July of 2002. Greater amounts of rainfall in this desert region have historically been associated with El Niño events. Previous studies of an unusual paleoflood deposit in this region have concluded that it is the product of El Niño-generated precipitation falling on seismically disturbed landscapes. The effects of the 2001 earthquake and 2002 rainstorm support that conclusion.


End-evaporation dynamics revisited.
We present analytical results on the so-called end-evaporation kinetics in equilibrium polymeric systems following a temperature jump (T jump). A T jump prepares the system with a nonequilibrium length distribution, after which it relaxes back to its equilibrium state. Starting from a master equation, we develop a mean-field analytical theory based on a generating function approach, which allows explicit approximate expressions for the monomer and dimer concentrations to be derived in a discrete setting; the concentrations of the other chains as well as the average chain length were shown to be entirely expressible in terms of the monomer and dimer concentrations. We find that the calculated monomer and dimer concentrations as well as the average chain length are in good agreement with numerical simulation results and do not suffer from some of the defects of earlier continuum theories. Furthermore, the relaxation was shown to take place in three different stages. The first stage comprises the very fast relaxation of the monomers to almost their equilibrium concentration; the other polymer chains have hardly relaxed. During the second stage, which is highly nonlinear, a redistribution of material at practically constant monomer density takes place. Only in the final stage of the relaxation process the chain concentrations approach their true equilibrium values. In this stage there are only very small shifts in the concentrations of chains, which are governed by extremely slow "indirect" monomer-mediated processes.


Treatment of anxiety in patients with coronary heart disease: Rationale and design of the UNderstanding the benefits of exercise and escitalopram in anxious patients WIth coroNary heart Disease (UNWIND) randomized clinical trial.
Anxiety is highly prevalent among patients with coronary heart disease (CHD), and there is growing evidence that high levels of anxiety are associated with worse prognosis. However, few studies have evaluated the efficacy of treating anxiety in CHD patients for reducing symptoms and improving clinical outcomes. Exercise and selective serotonin reuptake inhibitors have been shown to be effective in treating patients with depression, but have not been studied in cardiac patients with high anxiety. The UNWIND trial is a randomized clinical trial of patients with CHD who are at increased risk for adverse events because of comorbid anxiety. One hundred fifty participants with CHD and elevated anxiety symptoms and/or with a diagnosed anxiety disorder will be randomly assigned to 12 weeks of aerobic exercise (3×/wk, 35 min, 70%-85% VO2peak), escitalopram (5-20 mg qd), or placebo. Before and after 12 weeks of treatment, participants will undergo assessments of anxiety symptoms and CHD biomarkers of risk, including measures of inflammation, lipids, hemoglobin A1c, heart rate variability, and vascular endothelial function. Primary outcomes include post-intervention effects on symptoms of anxiety and CHD biomarkers. Secondary outcomes include clinical outcomes (cardiovascular hospitalizations and all-cause death) and measures of quality of life. The UNWIND trial (ClinicalTrials.gov NCT02516332) will evaluate the efficacy of aerobic exercise and escitalopram for improving anxiety symptoms and reducing risk for adverse clinical events in anxious CHD patients.


Clinical Study of Bone Regeneration by Conditioned Medium From Mesenchymal Stem Cells After Maxillary Sinus Floor Elevation.
This clinical study was undertaken to evaluate the safety of use of the secretome of bone marrow-derived mesenchymal stem cells (MSC-CM) for maxillary sinus floor elevation (SFE). MSC-CM was prepared from conditioned medium from human bone marrow-derived MSCs. Six partially edentulous patients were enrolled in the study. MSC-CM was mixed with porous beta-tricalcium phosphate (β-TCP) and implanted in 4 patients (experimental group), whereas only β-TCP was implanted in the other 2 patients (control group). Six months after SFE, bone biopsies and histological assessments were performed. Bone formation was clinically confirmed in all cases. Although Hounsfield units in computed tomography images were not significantly different between the groups, histological analysis revealed a significant difference in newly formed bone area between the groups. In particular, bone volume in the center of the augmented area was significantly greater in the MSC-CM group. Newly formed bone consisted of lamellar bone in the MSC-CM group but woven bone in the β-TCP group. The secretome of bone marrow-derived mesenchymal stem cells (MSC-CM) was used safely and has great osteogenic potential for regenerative medicine of bone.


Pentamidine-induced acute pancreatitis in a patient with AIDS.
We report pentamidine-induced acute pancreatitis in a patient with the acquired immunodeficiency syndrome (AIDS). The course of this pancreatitis was prolonged but favorable. Pentamidine was detected in serum as late as one month after discontinuation of therapy. The special pharmacokinetics of this drug may account for the potential severity of pentamidine-induced acute pancreatitis.


Tailored HCCH-TOCSY experiment for resonance assignment in the proximity of a paramagnetic center.
The presence of a paramagnetic center may disturb both coherent and incoherent communication between nuclear spins that are affected, to some extent, by the hyperfine interaction. This is a limiting factor to an extensive use of paramagnetic probes in NMR spectroscopy to enhance partial alignment and to exploit cross correlation effects and pseudocontact shifts. We propose here an HCCH-TOCSY experiment tailored to identify spin systems involving resonances that are partly or completely affected by hyperfine interaction. The efficiency of polarization transfer steps when fast relaxing nuclei are involved is discussed. The sequence is tested for the protein Calbindin D(9k), in which one of the two native Ca2+ ions is replaced by the paramagnetic Ce3+ ion as well as for the oxidized form of cytochrome b(562).


[Standardization of diagnosis and therapy in whiplash injuries of the cervical vertebrae].
In this work it is shown a standard diagnostic and therapeutic approach with the patient with stinging neck injury with goal to achieve a protocol for grouping injuries in those categories according to which we will proceed in further diagnostic and treatment, and letting out diagnoses as soon as possible in time period within the rational apply of available diagnostic procedures. The result of installing standardized protocol is the connection of the standard in diagnostic and therapy with safer triage of injured, standard therapy and getting precious time which we could use in treating a patient which will be helped with the treatment itself. In further diagnostic search it is out of most important question to define biomechanical limit of non dangerous in the stinging neck injury which will help to make a line between real injuries and renthal demands. In the therapeutic meaning, the injured patient is to be returned into the activity as soon as possible and certainly not after all the results have been back to normal.


Escape of metastasizing clonal tumor cell variants from tumor-specific cytolytic T lymphocytes.
A metastasizing variant of a chemically induced lymphoma from a DBA/2 mouse is shown to carry a distinct tumor-associated transplantation antigen (TATA), which can be recognized by syngeneic secondary anti-tumor cytolytic T lymphocytes (CTL). During metastasis of twice-cloned cell lines of this tumor, variants develop that are specifically immunoresistant to lysis by anti-tumor CTL. The variants are detected in the spleen of normal syngeneic mice. They remain stable over long-term passage in tissue culture. The high frequency with which these immunoresistant metastatic variants develop was found to explain the relative ineffectiveness of specific immunization against this metastatic tumor. Compared with organ-selective metastatic variants, the immunoresistant tumor variants seem to arise with a much higher frequency. The change in TATA expression described here differs from antibody-induced antigenic modulation in that it is more stable and genetically transmitted.


Effects of hCG administration on corpus luteum development and plasma sex steroid hormone concentration in beef heifers differ according to the locational relationships of the original corpus luteum and the first-wave dominant follicle.
The aims of this study were to compare the effects of an intramuscular human chorionic gonadotropin (hCG) administration on corpus luteum (CL) development, plasma progesterone (P4) and estradiol (E2) concentration in ipsilateral (first-wave dominant follicle [W1DF] in the same ovary as the CL) and contralateral (W1DF and CL in opposite ovaries) cattle. Cross-bred beef heifers (Holstein × Japanese black, n=83) with synchronized ovulation were randomly assigned to either treatment with 1,500 IU hCG or no treatment on day 5 post-ovulation and were subdivided into ipsilateral (hCG treatment, n=21; no treatment, n=23) or contralateral (hCG treatment, n=17; no treatment, n=17) groups. Five heifers were excluded from the study, as they presented with double ovulation in response to hCG treatment. The effects of hCG treatment, location (ipsilateral and contralateral), and the number of days post-ovulation (days 5, 7, and 14) were analyzed using three-way ANOVA. hCG treatment significantly increased CL diameter on day 7 and plasma P4 concentration on days 7 and 14 in the contralateral group, but not the ipsilateral group. In contrast, hCG treatment decreased plasma E2 concentration on days 7 and 14 in both groups. In summary, our results indicate that the hCG treatment more significantly promoted CL development and increased plasma P4 concentration in the contralateral than in the ipsilateral group.


Carbohydrate-deficient transferrin, a marker for chronic alcohol consumption in different ethnic populations.
Serum levels of carbohydrate-deficient transferrin (CDT) were determined in a racially mixed population of 107 alcoholics, 18 healthy, nonalcoholic control subjects, 62 abstinent alcoholics, and in 64 Caucasian patients with various nonalcoholic liver diseases. The upper limit of normal CDT levels was 80 mg/liter (2 SD above the mean). CDT values exceeding this level were found in more than 80% of Black, Puerto Rican, and Caucasian alcoholics who had consumed greater than or equal to 50 g of alcohol/day for 1 month or longer prior to testing. Puerto Rican alcoholics had higher CDT values than the Black and Caucasian ethnic groups; however, these differences were significant only when compared to the Black population. Of 64 patients with nonalcoholic liver diseases, one individual with chronic active hepatitis (CAH) with an alcohol consumption of 20 g/day, and 10 of 26 subjects with primary biliary cirrhoses (PBC), who claimed to consume either no or only occasional moderate amounts of alcohol, had CDT levels ranging from 81 to 144 mg/liter. Seven of these individuals were in advanced stages of PBC. Total transferrin levels were variable and not significantly different in all subject groups studied. CDT/total transferrin ratios were increased in most patients with abnormal amounts of CDT, and there was a significant correlation between these ratios and CDT levels in all study groups. Serum enzyme parameters as well as red blood cell mean corpuscular volumes did not correlate with CDT values.(ABSTRACT TRUNCATED AT 250 WORDS)


Pathology Residents Comprise Inspection Team for a CAP Self-Inspection.
We report our experience at the University of Florida in which residents and fellows served as the inspection team for a College of American Pathologists (CAP) self-inspection. We aimed to determine whether the CAP self-inspection could serve as a learning opportunity for pathology residents and fellows. To prepare for the inspection, we provided a series of 4 lunchtime seminars covering numerous laboratory management topics relating to inspections and laboratory quality. Preparation for the inspection began approximately 4 months prior to the date of the inspection. The intent was to simulate a CAP peer inspection, with the exception that the date was announced. The associate residency program director served as the team leader. All residents and fellows completed inspector training provided by CAP, and the team leader completed the team leader training. A 20 question pre- and posttest was administered; additionally, an anonymous survey was given after the inspection. The residents' and fellows' posttest scores were an average of 15% higher than on the pretest (P < .01). The surveys as well as subjective comments were overwhelmingly positive. In conclusion, the resident's and fellow's experience as an inspector during a CAP self-inspection was a useful tool to learn accreditation and laboratory management.


Assessing process of paediatric care in a resource-limited setting: a cross-sectional audit of district hospitals in Rwanda.
Routine assessment of quality of care helps identify deficiencies which need to be improved. While gaps in the emergency care of children have been documented across sub-Saharan Africa, data from Rwanda are lacking. To assess the care of sick infants and children admitted to Rwandan district hospitals and the extent to which it follows currently recommended clinical practice guidelines in Rwanda. Data were gathered during a retrospective cross-sectional audit of eight district hospitals across Rwanda in 2012/2013. Medical records were randomly selected from each hospital and were reviewed to assess the process of care, focusing on the leading causes of under-5 mortality, including neonatal conditions, pneumonia, malaria and dehydration/diarrhoea. Altogether, 522 medical records were reviewed. Overall completion of a structured neonatal admission record was above 85% (range 78.6-90.0%) and its use was associated with better documentation of key neonatal signs (median score 6/8 and 2/8 when used and not used, respectively). Deficiencies in the processes of care were identified across hospitals and there were rural/urban disparities for some indicators. For example, neonates admitted to urban district hospitals were more likely to receive treatment consistent with currently recommended guidelines [e.g. gentamicin (OR 2.52, 95% CI 1.03-6.43) and fluids (OR 2.69, 95% CI 1.2-6.2)] than those in rural hospitals. Likewise, children with pneumonia admitted to urban hospitals were more likely to receive the correct dosage of gentamicin (OR 4.47, 95% CI 1.21-25.1) and to have their treatment monitored (OR 3.75, 95% CI 1.57-8.3) than in rural hospitals. Furthermore, children diagnosed with malaria and admitted to urban hospitals were more likely to have their treatment (OR 2.7, 95% CI 1.15-6.41) monitored than those in rural hospitals. Substantial gaps were identified in the process of neonatal and paediatric care across district hospitals in Rwanda. There is a need to (i) train health care professionals in providing neonatal and paediatric care according to nationally adopted clinical practice guidelines (e.g. ETAT+); (ii) establish a supervision and mentoring programme to ensure that the guidelines are available and used appropriately in district hospitals; and (iii) use admission checklists (e.g. neonatal and paediatric admission records) in district hospitals.


The Potato Yam Phyllosphere Ectosymbiont Paraburkholderia sp. Msb3 Is a Potent Growth Promotor in Tomato.
The genus Paraburkholderia includes a variety of species with promising features for sustainable biotechnological solutions in agriculture through increasing crop productivity. Here, we present a novel Paraburkholderia isolate, a permanent and predominant member of the Dioscoreae bulbifera (yam family, Dioscoreaceae) phyllosphere, making up to 25% of the microbial community on leaf acumens. The 8.5 Mbp genome of isolate Msb3 encodes an unprecedented combination of features mediating a beneficial plant-associated lifestyle, including biological nitrogen fixation (BNF), plant hormone regulation, detoxification of various xenobiotics, degradation of aromatic compounds and multiple protein secretion systems including both T3SS and T6SS. The isolate exhibits significant growth promotion when applied to agriculturally important plants such as tomato, by increasing the total dry biomass by up to 40%. The open question about the "beneficial" nature of this strain led us to investigate ecological and generic boundaries in Burkholderia sensu lato. In a refined phylogeny including 279 Burkholderia sensu lato isolates strain Msb3 clusters within Clade I Paraburkholderia, which also includes few opportunistic strains that can potentially act as pathogens, as revealed by our ecological meta-data analysis. In fact, we demonstrate that all genera originating from the "plant beneficial and environmental" (PBE) Burkholderia species cluster include opportunists. This indicates that further functional examinations are needed before safe application of these strains in sustainable agricultural settings can be assured.


What Factors Influence States' Capacity to Report Children's Health Care Quality Measures? A Multiple-Case Study.
Objectives The objective of this study was to describe factors that influence the ability of state Medicaid agencies to report the Centers for Medicare & Medicaid Services' (CMS) core set of children's health care quality measures (Child Core Set). Methods We conducted a multiple-case study of four high-performing states participating in the Children's Health Insurance Program Reauthorization Act (CHIPRA) Quality Demonstration Grant Program: Illinois, Maine, Pennsylvania, and Oregon. Cases were purposively selected for their diverse measurement approaches and used data from 2010 to 2015, including 154 interviews, semiannual grant progress reports, and annual public reports on Child Core Set measures. We followed Yin's multiple-case study methodology to describe how and why each state increased the number of measures reported to CMS. Results All four states increased the number of Child Core Set measures reported to CMS during the grant period. Each took a different approach to reporting, depending on the available technical, organizational, and behavioral inputs in the state. Reporting capacity was influenced by a state's Medicaid data availability, ability to link to other state data systems, past experience with quality measurement, staff time and technical expertise, and demand for the measures. These factors were enhanced by CHIPRA Quality Demonstration grant funding and other federal capacity building activities, as hypothesized in our conceptual framework. These and other states have made progress reporting the Child Core Set since 2010. Conclusion With financial support and investment in state data systems and organizational factors, states can overcome challenges to reporting most of the Child Core Set measures.


[Surgical therapy of Crohn's disease: observations on 63 patients].
The purpose of our retrospective study is to evaluate the correct indications for the surgical therapy of Crohn's disease. Our case series consists of 63 patients admitted to our Surgery Department from January 1, 1973 to December 2002 with a diagnosis of Crohn's disease. Of the 56 operated patients, 43 patients were followed-up. For an objective evaluation of the Crohn's disease activity, the Crohn's Disease Activity Index (CDAI) was used. Surgical treatment has been carried out in 56 cases: in 29 cases of intestinal occlusion a minimal gut resection was performed; in the 26 cases of perforation a suture of the perforation was preferred, with a drainage of the peritoneal cavity and a toilette of abscess when it was present, and in 1 case an ileocolic resection was performed. Only 1 case showed a CDAI score >150 (153.63). This shows that in all the other cases the surgical and medical treatment has led to a satisfactory control of the disease. A relapse has been observed in 17 patients after an average period of 5 years without showing signs of disease. It is suggested that Crohn's disease therapy should be mainly of a medical nature and surgical treatment should be reserved for complicated cases.


Abnormal postexercise systolic blood pressure response is a good indicator of impaired left ventricular filling during supine cycle ergometer exercise in patients with coronary artery disease.
To determine whether the postexercise systolic blood pressure (SBP) response is a useful marker of left ventricular filling abnormalities, supine leg exercise testing was conducted in 14 control subjects and 70 patients with coronary artery disease (CAD). An abnormal postexercise SBP response (the ratio of SBP after 3 min of recovery to the peak exercise SBP) was defined as 0.85 or more, which represented the cutoff point with the highest sensitivity and specificity for prediction of pulmonary artery wedge pressure (PAWP) of at least 20 mmHg at peak exercise in CAD patients. There was a significant difference between the SBP ratios of the two groups (Control, 0.72 +/- 0.05; CAD, 0.86 +/- 0.13; p < 0.01). There was no significant difference between the PAWP of the two groups at rest, but the PAWP at peak exercise was significantly higher in the CAD group (20.2 +/- 8.9 mmHg) than in the control group (11.5 +/- 4.0 mmHg)(p < 0.01). PAWP at peak exercise was > or = 20 mmHg in 35 (50%) of the 70 CAD subjects. The SBP ratio was significantly correlated with PAWP at peak exercise (r = 0.67, p < 0.01) in the CAD group, but not in the control group. An SBP ratio of > or = 0.85 showed a sensitivity of 80% and a specificity of 80% for predicting a peak exercise PAWP of > or = 20 mmHg in CAD patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Gastroesophageal reflux disease presenting with intractable nausea.
Typical symptoms of gastroesophageal reflux disease are heartburn and regurgitation. A subset of patients present with atypical symptoms, such as chest pain, cough, wheezing, and hoarseness. To review the clinical presentation and treatment of patients who presented with nausea as the primary symptom of gastroesophageal reflux disease. Case series. Outpatient department of a university hospital. 10 outpatients who had chronic, intractable nausea and had not responded to empirical therapies. Patients were evaluated by esophagogastroduodenoscopy, 24-hour esophageal pH studies, gastric-emptying tests, electrogastrography, or a Bernstein test. Abnormal acid reflux was found to be the cause of intractable nausea in all 10 patients. In 5 of the 10 patients, esophagitis was documented by esophagogastroduodenoscopy. Six patients had abnormal results on the 24-hour esophageal pH study. In these 6 patients, 32 of 33 episodes of nausea were accompanied by an episode of acid reflux. One patient had positive results on the Bernstein test. Nausea resolved after treatment with omeprazole in 7 patients, after treatment with cisapride or ranitidine in 2 patients, and after Nissen fundoplication in 1 patient. Intractable nausea is an atypical symptom that can occur in a subset of patients with gastroesophageal reflux disease. A 24-hour esophageal pH study should be considered in patients who have unexplained nausea but normal findings on esophagogastroduodenoscopy, a gastric-emptying test, and electrogastrography. Nausea related to gastroesophageal reflux disease resolves or is markedly reduced with proton-pump inhibitors or promotility drugs.


Total Protein Profile and Drug Resistance in Candida albicans Isolated from Clinical Samples.
This study was done to assess the antifungal susceptibility of clinical isolates of Candida albicans and to evaluate its total protein profile based on morphological difference on drug resistance. Hundred and twenty clinical isolates of C. albicans from various clinical specimens were tested for susceptibility against four antifungal agents, namely, fluconazole, itraconazole, amphotericin B, and ketoconazole. A significant increase of drug resistance in clinical isolates of C. albicans was observed. The study showed 50% fluconazole and itraconazole resistance at 32 μg mL(-1) with a MIC50 and MIC90 values at 34 and 47 and 36 and 49 μg mL(-1), respectively. All isolates were sensitive to amphotericin B and ketoconazole. The SDS-PAGE protein profile showed a prevalent band of ~52.5 kDa, indicating overexpression of gene in 72% strains with fluconazole resistance. Since the opportunistic infections of Candida spp. are increasing along with drug resistance, the total protein profile will help in understanding the evolutionary changes in drug resistance and also to characterize them.


Construction of metal-ligand-coordinated multilayers and their selective separation behavior.
In this article, a layer-by-layer (LbL)-assembled coordination multilayer on planar and 3D substrates was explored by the alternate deposition of a transition-metal-containing polyelectrolyte and a ligand-containing polymer via the formation of complexes. The metal-ligand coordination between the building blocks of Co(2+)-exchanged poly(styrene sulfonate) (PSS) and poly(4-vinyl pyridine) (P4 VP) has been demonstrated using UV-vis, FTIR, and XPS. The film thickness, structure, and morphology as well as the wettability as a function of bilayer number have been systematically investigated by profilometry, SEM, AFM, and contact angle analyzers. For the purpose of separation applications, the metal-ligand-coordinated multilayer was assembled on both flat sheet and hollow fiber polymeric porous substrates using a dynamic pressure-driven LbL technique. It was demonstrated that the LbL-assembled PSS(Co)(1/2)/P4 VP multilayer membrane had high dehydration performance with respect to different solvent-water mixtures; it also had aromatic compound permselectivity from aromatic-aliphatic hydrocarbons and water-softening capacity. Meanwhile, the successful assembly of multilayers on hollow fibers indicates that the dynamic pressure-driven LbL technique is a unique approach to the construction of multilayers on porous 3-D substrates. Therefore, the metal-ligand-coordinated self-assembly could emerge as a powerful technique for the preparation of a range of separation membranes in different types of modules.


Pediatric endoscopy training across Europe: a survey of the ESPGHAN National Societies Network 2016-2019.
Background and study aims The ability to perform endoscopy procedures safely and effectively is a key aspect of quality clinical care in Pediatric Gastroenterology, Hepatology and Nutrition (PGHN). The aim of this survey, which was part of a global survey on PGHN training in Europe, was to assess endoscopy training opportunities provided across Europe. Methods Responses to standardized questions related to endoscopy training were collected from training centers across Europe through the presidents/representatives of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition National Societies from June 2016 to December 2019. Results A total of 100 training centers from 19 countries participated in the survey. In 57 centers, the endoscopy suit was attached to the PGHN center, while in 23, pediatric endoscopies were performed in adult endoscopy facilities. Ninety percent of centers reported the availability of specialized endoscopy nurses and 96 % of pediatric anesthetists. Pediatric endoscopies were performed by PGHN specialists in 55 centers, while 31 centers reported the involvement of an adult endoscopist and 14 of a pediatric surgeon. Dividing the number of procedures performed at the training center by the number of trainees, ≤ 20 upper, lower, or therapeutic endoscopies per trainee per year were reported by 0 %, 23 %, and 56 % of centers, respectively, whereas ≤ 5 wireless capsule endoscopies per trainee per year by 75 %. Only one country (United Kingdom) required separate certification of competency in endoscopy. Conclusions Differences and deficiencies in infrastructure, staffing, and procedural volume, as well as in endoscopy competency assessment and certification, were identified among European PGHN training centers limiting training opportunities in pediatric endoscopy.


Historical spatial reconstruction of a spawning-aggregation fishery.
Aggregations of individual animals that form for breeding purposes are a critical ecological process for many species, yet these aggregations are inherently vulnerable to exploitation. Studies of the decline of exploited populations that form breeding aggregations tend to focus on catch rate and thus often overlook reductions in geographic range. We tested the hypothesis that catch rate and site occupancy of exploited fish-spawning aggregations (FSAs) decline in synchrony over time. We used the Spanish mackerel (Scomberomorus commerson) spawning-aggregation fishery in the Great Barrier Reef as a case study. Data were compiled from historical newspaper archives, fisher knowledge, and contemporary fishery logbooks to reconstruct catch rates and exploitation trends from the inception of the fishery. Our fine-scale analysis of catch and effort data spanned 103 years (1911-2013) and revealed a spatial expansion of fishing effort. Effort shifted offshore at a rate of 9.4 nm/decade, and 2.9 newly targeted FSAs were reported/decade. Spatial expansion of effort masked the sequential exploitation, commercial extinction, and loss of 70% of exploited FSAs. After standardizing for improvements in technological innovations, average catch rates declined by 90.5% from 1934 to 2011 (from 119.4 to 11.41 fish/vessel/trip). Mean catch rate of Spanish mackerel and occupancy of exploited mackerel FSAs were not significantly related. Our study revealed a special kind of shifting spatial baseline in which a contraction in exploited FSAs occurred undetected. Knowledge of temporally and spatially explicit information on FSAs can be relevant for the conservation and management of FSA species.


Phosphorylation of mitogen-activated protein kinase by one-trial and multi-trial classical conditioning.
The pathway supporting the conditioned stimulus (CS) is one site of plasticity that has been studied extensively in conditioned Hermissenda. Several signal transduction pathways have been implicated in classical conditioning of this preparation, although the major emphasis has been on protein kinase C. Here we provide evidence for the activation and phosphorylation of a mitogen-activated protein kinase (MAPK) pathway by one-trial and multi-trial conditioning. A one-trial in vitro conditioning procedure consisting of light (CS) paired with the application of 5-HT results in the increased incorporation of 32PO4 into proteins detected with two-dimensional gel electrophoresis. Two of the phosphoproteins have molecular weights of 44 and 42 kDa, consistent with extracellular signal-regulated protein kinases (ERK1 and ERK2). Phosphorylation of the 44 and 42 kDa proteins by one-trial conditioning was inhibited by pretreatment with PD098059, A MEK1 (ERK-Activating kinase) inhibitor. Assays of ERK activity with brain myelin basic protein as a substrate revealed greater ERK activity for the group that received one-trial conditioning compared with an unpaired control group. Western blot analysis of phosphorylated ERK using antibodies recognizing the dually phosphorylated forms of ERK1 and ERK2 showed an increase in phosphorylation after one-trial conditioning compared with unpaired controls. The increased phosphorylation of ERK after one-trial conditioning was blocked by pretreatment with PD098059. Hermissenda that received 10 or 15 conditioning trials showed significant behavioral suppression compared with pseudo-random controls. After conditioning and behavioral testing, the conditioned animals showed significantly greater phosphorylation of ERK compared with the pseudo-random controls. These results show that the ERK-MAPK signaling pathway is activated in Pavlovian conditioning of Hermissenda.


[Clothing and heat disorder].
The influence of the clothing material properties(like water absorbency and rapid dryness, water vapor absorption, water vapor permeability and air permeability) and the design factor of the clothing(like opening condition and fitting of clothing), which contributed to prevent heat disorder, was outlined. WBGT(wet-bulb globe temperature) is used to show a guideline for environmental limitation of activities to prevent heat disorder. As the safety function is more important than thermal comfort for some sportswear and protective clothing with high cover area, clothing itself increases the risk of heat disorder. WBGT is corrected by CAF (clothing adjustment factor) in wearing such kind of protective clothing.


Relationship of mannitol challenge to methacholine challenge and inflammatory markers in persistent asthmatics receiving inhaled corticosteroids.
Mannitol is a novel osmotic indirect bronchial challenge agent used to aid asthma diagnosis and management and is thought to reflect underlying inflammatory processes in asthma. Our objective was to evaluate relationships between mannitol airway hyperresponsiveness (AHR) and other measures of airway inflammation as well as direct-acting methacholine challenge in persistent asthmatics receiving inhaled corticosteroids. We analysed screening data of mild to moderate persistent asthmatics, all receiving inhaled corticosteroids (ICS), who had mannitol and/or methacholine challenges, fractional exhaled nitric oxide (FeNO), and salivary eosinophilic cationic protein (ECP) performed as part of the same screen. Mannitol AHR was grouped by PD(10) (cumulative provocative dose required to produce a 10 % fall in FEV(1)): mild (315-635 mg), moderate (75-315 mg), and severe (0-75 mg). FeNO groups were low (<25 ppb), medium (25-50 ppb), and high (> 50 ppb) and methacholine PC(20) (provocative concentration of methacholine required to cause a 20 % fall in FEV(1)) groups were mild (2-8 mg/ml), moderate (0.5-2 mg/ml), and severe (0-0.5 mg/ml). Mannitol PD(10) groups were significantly different overall for FeNO (p = 0.023): 43 % higher in the severe vs. the mild group. There was a significant overall difference for methacholine PC(20) (p = 0.006): a 2.1 doubling dilution difference between severe vs. mild mannitol groups. FeNO groups were significantly different overall for mannitol PD(10) (p = 0.01) and methacholine PC(20) (p = 0.029). Methacholine PC(20) groups were significantly different overall for mannitol PD(10) (p < 0.001) and FeNO (p = 0.005). No significant differences were found across any groups for salivary ECP, FEV(1) % predicted, or ICS dose. Mannitol PD(10), methacholine PC(20), and FeNO as continuous variables all correlated with each other. Mannitol challenge reflects underlying inflammation using FeNO and direct AHR using methacholine. Thus, mannitol may be a useful screening tool for the assessment of asthmatic patients receiving inhaled corticosteroids.


Cuprous Oxide Catalyzed Oxidative C-C Bond Cleavage for C-N Bond Formation: Synthesis of Cyclic Imides from Ketones and Amines.
Selective oxidative cleavage of a C-C bond offers a straightforward method to functionalize organic skeletons. Reported herein is the oxidative C-C bond cleavage of ketone for C-N bond formation over a cuprous oxide catalyst with molecular oxygen as the oxidant. A wide range of ketones and amines are converted into cyclic imides with moderate to excellent yields. In-depth studies show that both α-C-H and β-C-H bonds adjacent to the carbonyl groups are indispensable for the C-C bond cleavage. DFT calculations indicate the reaction is initiated with the oxidation of the α-C-H bond. Amines lower the activation energy of the C-C bond cleavage, and thus promote the reaction. New insight into the C-C bond cleavage mechanism is presented.


Community psychiatry and the population explosion.
Although excessive population has long been a dilemma in certain areas of the world, current rates of growth present a global threat to all nations. Arguments based on economics, world peace, individual freedom, humanism and the preservation of life's amenities all point to the urgent need for programs to control birth rates. This applies to the United States also, although we have the advantage of a relatively high cultural and economic level from which to attack the problem. Modern psychiatry is increasingly committed to the Community Mental Health concept, which in part implies greater involvement with the element of the population that is socially and economically at a disadvantage. Effective treatment cannot ignore the effects on the patient of intolerable reality situations, often produced by successive unwanted pregnancies. In addition, a positive approach to family planning by psychiatrists and social workers will provide the structure needed for truly preventive psychiatry; as our knowledge of the determinants of psychosis, delinquency and mental retardation expands, selective counseling can do much to prevent these family and social tragedies. Both as world citizens and as practitioners of a profession, psychiatrists cannot afford to delay pledging their resources to the solution of so compelling a problem.


De-regulation of gene expression and alternative splicing affects distinct cellular pathways in the aging hippocampus.
Aging is accompanied by gradually increasing impairment of cognitive abilities and constitutes the main risk factor of neurodegenerative conditions like Alzheimer's disease (AD). The underlying mechanisms are however not well understood. Here we analyze the hippocampal transcriptome of young adult mice and two groups of mice at advanced age using RNA sequencing. This approach enabled us to test differential expression of coding and non-coding transcripts, as well as differential splicing and RNA editing. We report a specific age-associated gene expression signature that is associated with major genetic risk factors for late-onset AD (LOAD). This signature is dominated by neuroinflammatory processes, specifically activation of the complement system at the level of increased gene expression, while de-regulation of neuronal plasticity appears to be mediated by compromised RNA splicing.


Aberrant DNA methylation but not mutation of CITED4 is associated with alteration of HIF-regulated genes in breast cancer.
CBP/p300-interacting transactivator with ED-rich carboxy-terminal domain 4 (CITED4) inhibits HIF-1α transactivation by binding to CBP/p300. We hypothesised that either somatic mutation or hypermethylation of the CITED4 gene underlies CITED4 down-regulation and thus enhanced HIF-1α expression in some breast tumours. DNA sequencing was used to screen for somatic mutations. Methylation-sensitive high resolution melting was performed to identify CITED4 methylation. RT-qPCR was carried out to measure the expression of CITED4 and selected HIF downstream targets. HIF-1α and downstream gene expression was assessed with immunohistochemistry. No somatic mutations of CITED4 were identified in 10 tumour cell lines and 100 breast carcinomas. However, CITED4 promoter methylation was identified in 5/168 breast carcinomas (four infiltrating ductal carcinomas and one infiltrating lobular carcinoma) and in 3/10 breast cancer cell lines (MDA-MB-453, MDA-MB-231 and Hs578T). CITED4 mRNA expression in cell lines was inversely correlated with DNA methylation. CITED4 mRNA expression was significantly increased in all three cell lines after 5-aza-2-deoxycytidine (DAC) treatment. Treatment of the MDA-MB-231 cell line with DAC followed by hypoxia (0.1% O²) resulted in down-regulation of expression of the HIF-1α downstream genes VEGFA and SLC2A1 (P = 0.0029). HIF-1α downstream SLC2A1 was decreased (P = 0.021) after CITED4 was re-expressed under hypoxia. Loss of expression of CITED4 in breast cancer may be due to DNA methylation but is unlikely to be due to mutation. Demethylation and histone modification can potentially reactivate CITED4 gene expression in some breast cancers and lead to changes in tumour behaviour. Strategies such as HDAC inhibitors may overcome this effect.


Atheroma: links with antiphospholipid antibodies, Hughes syndrome and lupus.
Antiphospholipid antibodies (aPL) are found in a variety of autoimmune diseases, and are thought to predispose to arterial and venous thrombosis. These antibodies, when investigated in different assays in vitro, activate endothelial cells and promote uptake of modified LDL to macrophages. These observations suggest that aPL can contribute to atheroma development by targeting some of the sequential steps that constitute early atherogenesis. If substantiated by large-scale clinical trials, the pro-atherogenic properties of aPL may merit screening and intervention programs in selected populations.


Ce-Doped NiFe-Layered Double Hydroxide Ultrathin Nanosheets/Nanocarbon Hierarchical Nanocomposite as an Efficient Oxygen Evolution Catalyst.
Developing convenient doping to build highly active oxygen evolution reaction (OER) electrocatalysts is a practical process for solving the energy crisis. Herein, a facile and low-cost in situ self-assembly strategy for preparing a Ce-doped NiFe-LDH nanosheets/nanocarbon (denoted as NiFeCe-LDH/CNT, LDH = layered double hydroxide and CNT = carbon nanotube) hierarchical nanocomposite is established for enhanced OER, in which the novel material provides its overall advantageous structural features, including high intrinsic catalytic activity, rich redox properties, high, flexible coordination number of Ce3+, and strongly coupled interface. Further experimental results indicate that doped Ce into NiFe-LDH/CNT nanoarrays brings about the reinforced specific surface area, electrochemical surface area, lattice defects, and the electron transport between the LDH nanolayered structure and the framework of CNTs. The effective synergy prompts the NiFeCe-LDH/CNT nanocomposite to possess superior OER electrocatalytic activity with a low onset potential (227 mV) and Tafel slope (33 mV dec-1), better than the most non-noble metal-based OER electrocatalysts reported. Therefore, the combination of the remarkable catalytic ability and the facile normal temperature synthesis conditions endows the Ce-doped LDH nanocomposite as a promising catalyst to expand the field of lanthanide-doped layered materials for efficient water-splitting electrocatalysis with scale-up potential.


Primary open reduction and internal fixation with headless compression screws in the treatment of Chinese patients with acute Lisfranc joint injuries.
Although primary open anatomic reduction and stable internal fixation has become a standard treatment principle of Lisfranc joint injuries, there are still some debates existed among surgeons as to the most appropriate treatment of this injury. The aim of this cohort study was to analyze the early (mean, 3.2 years) clinical and radiographic outcomes of one surgeon's experience associated with a standardized protocol of open reduction and internal fixation using headless compression screws (HCS) in a consecutive series of Chinese patients with Lisfranc joint injuries. This study is to retrospectively evaluate the clinical and radiographic outcomes of a series of Chinese patients with Lisfranc joint injuries that underwent open reduction and internal fixation with HCS. There were 29 patients (30 feet) included in our study. The average score of American Orthopaedic Foot and Ankle Society Midfoot score and the Visual Analog Pain Scale were 80.6 and 2.4 points at the final follow-up point, respectively. Anatomic initial reduction was obtained in 26 patients (27 feet, 90%). At the last follow-up point, only one case had the loss of reduction. Posttraumatic osteoarthritis was observed in 10 patients (10 feet, 33%), and 2 of them (2 feet, 7%) were scheduled for arthrodesis because of persistent pain. Our results have shown that fixation of an unstable tarsometatarsal joint with AO 3.0 mm HCS can provide the firm stability, the precise reduction of the joint, and satisfactory short-term clinical and radiographic outcomes without any screw breakage, although posttraumatic osteoarthritis in the midfoot is still a significant challenge for orthopedic surgeons.


Short communication: Changes in micromineral, magnesium, cytokine, and cortisol concentrations in blood of dairy goats following intramammary inoculation with Staphylococcus aureus.
The aim of this study was to investigate mineral metabolism and immune response in dairy goats following intramammary inoculation with varying doses of Staphylococcus aureus. Blood samples were collected at 0, 2, 4, 8, 12, 24, 48, and 72 h after intramammary inoculation. Lowered plasma Fe concentrations were observed from 12 to 24 h postinoculation in groups SAA (Staph. aureus at 10(4) cfu, n = 5) and SAB (Staph. aureus at 10(8) cfu, n = 5). Plasma Cu concentrations increased in group SAB 2 h after inoculation and maintained greater concentrations until the end of the experiment compared with the control group (phosphate-buffered saline, n = 5). Increased plasma Zn concentrations in group SAB were observed 48 h after inoculation, and the concentration was still greater 72 h after inoculation compared with the control group. Greater plasma Mg concentrations were detected in groups SAA and SAB compared with the control group at all timepoints after inoculation. Plasma Mg concentrations were generally greater in group SAA than in group SAB through 72 h (except at 2 h). Plasma tumor necrosis factor-alpha concentrations were unchanged following intramammary inoculation with Staph. aureus throughout the study. Plasma IL-6 concentrations in groups SAA and SAB increased gradually compared with the control group and peaked at 48 h after inoculation. In group SAB, serum cortisol concentrations started to increase from 8 h postinoculation and peaked at 12 h postinoculation. In conclusion, increasing the inoculum dose does not induce more rapid proinflammatory cytokine responses, whereas the data indicate that mineral metabolic alterations occur during the course of Staph. aureus mastitis in the goat.


Characterization of age-related changes in bovine CD8+ T-cells.
Evaluation of the changes induced by immunological interventions requires a baseline against which to compare those changes. The age-related changes in the CD8(+) T-cell population of cattle were studied. The results indicate that CD8(+) T-cells could be divided into γ/δ TCR1(+) and γ/δ TCR1(-) according to their expression of the γ/δ T-cell receptor. As a proportion, the CD8(+) γ/δ TCR1(+) population appears to increase with age. Within the CD8(+)γ/δ TCR1(-) a population of cells expressing a profile of surface molecules previously associated with effector memory T cells (CD45RO(+), CD62L(-), CD27(-), CD45RA(-) and CD28(-)) increases with age. Furthermore, a parallel increase with age in the proportion of CD8(+)CD45RO(+) T cells that express the cytotoxic granule protein perforin was observed. In peripheral tissues, namely lungs, it was found that the majority of CD8(+) T cells present expressed a phenotype indicative of previously primed T cells (high expression of CD45RO and perforin). In contrast, only a small population of memory CD8(+) T cells was present in lymphoid tissue where most of the CD8(+) T cells expressed a naïve phenotype. In conclusion, in cattle, like in human, CD8(+) T cells that express a phenotype associated with antigen experience accumulate with age that may play a role in immunocompetence as the individual ages.


ReMiND: Recovery of Missing Neuroimaging using Diffusion Models with Application to Alzheimer's Disease.
Missing data is a significant challenge in medical research. In longitudinal studies of Alzheimer's disease (AD) where structural magnetic resonance imaging (MRI) is collected from individuals at multiple time points, participants may miss a study visit or drop out. Additionally, technical issues such as participant motion in the scanner may result in unusable imaging data at designated visits. Such missing data may hinder the development of high-quality imaging-based biomarkers. Furthermore, when imaging data are unavailable in clinical practice, patients may not benefit from effective application of biomarkers for disease diagnosis and monitoring. To address the problem of missing MRI data in studies of AD, we introduced a novel 3D diffusion model specifically designed for imputing missing structural MRI (Recovery of Missing Neuroimaging using Diffusion models (ReMiND)). The model generates a whole-brain image conditional on a single structural MRI observed at a past visit or conditional on one past and one future observed structural MRI relative to the missing observation. Experimental results show that our method can generate high-quality individual 3D structural MRI with high similarity to ground truth, observed images. Additionally, images generated using ReMiND exhibit relatively lower error rates and more accurately estimated rates of atrophy over time in important anatomical brain regions compared with two alternative imputation approaches: forward filling and image generation using variational autoencoders. Our 3D diffusion model can impute missing structural MRI data at a single designated visit and outperforms alternative methods for imputing whole-brain images that are missing from longitudinal trajectories.


Chemical and Bacterial Components in Sake and Sake Production Process.
Together with the worldwide Washoku (traditional Japanese foods and drinks) boom, interest in sake, a traditional Japanese alcoholic drink, is increasing around the world. There are few scientific analyses and studies on the production of sake or the final product itself. We show the diversity of bacterial contaminants during sake production and investigated the effects of different ingredients on sake (for example, amino acids). The koji mold Aspergillus oryzae converts rice starch into sugars, and then, the sake yeast Saccharomyces cerevisiae converts the sugars to ethanol. Comparative studies of the bacterial flora of different sakes have shown that various bacterial species are detected, but that there are few frequently detected bacteria. In addition, the bacterial flora does not vary much during the process of sake brewing, after the koji (steamed rice covered with koji mold) and moto (fermentation starter) are mixed, suggesting that most bacteria contaminate the sake during the process of koji and moto production. Thus, there is the possibility that the contaminating bacteria may grow due to a relationship with the koji mold and/or the sake yeast. The flavor, taste, and quality of sakes differ, even between the same brands of sakes, which may be attributed to variations in the contaminating bacteria during sake production.


Systemic Inflammation Impairs Proliferation of Hippocampal Type 2 Intermediate Precursor Cells.
Neurogenesis is a plastic event modulated by external cues. Systemic inflammation decreases neurogenesis in the dentate gyrus (DG) in part through the proliferative restrain of neural precursor cells (NPCs). To evaluate if inflammation affects the cell cycle progression of particular populations of NPCs, we treated young-adult mice with a single i.p. injection of saline or 1 mg/kg LPS. After 7 days, we analysed proliferation of new BrdU+/DCX+ cells through immunohistochemistry. We extracted the hippocampus and performed a neurosphere assay and a flow cytometric analysis to evaluate proliferation and to identify the phase of the cell cycle in specific populations of DG-derived NPCs. We show that the number of BrdU+/DCX+ cells diminishes in the LPS-treated group and that the number of primary neurospheres derived from LPS-injected animals is significantly reduced compared to the saline-injected group. Flow cytometry revealed that inflammation does not affect the total number of Type 1 BLBP+/TBR2- cells, while the total number of Type 2 intermediate precursor cells (IPCs) (TBR2+) from the LPS-treated group was increased. Cell cycle analysis shows a decrease in the total rate of NPCs in phases S, G2 and M in the LPS-treated group. The percentage of Type 1 BLBP+/TBR2- cells in each cell cycle phase was not different between groups, while there was a fewer number of Type 2 TBR2+ cells in S/G2/M phase. These results show that inflammation alters the appropriate cell cycle progression of Type 2 IPCs, which may contribute to the decrease in the birth rate of DG neurons.


Transport of lactate and other short-chain monocarboxylates in the yeast Saccharomyces cerevisiae.
Saccharomyces cerevisiae IGC4072 grown in lactic acid medium transported lactate by an accumulative electroneutral proton-lactate symport with a proton-lactate stoichiometry of 1:1. The accumulation ratio measured with propionate increased with decreasing pH from ca. 24-fold at pH 6.0 to ca. 1,400-fold at pH 3.0. The symport accepted the following monocarboxylates (Km values at 25 degrees C and pH 5.5): D-lactate (0.13 mM), L-lactate (0.13 mM), pyruvate (0.34 mM), propionate (0.09 mM), and acetate (0.05 mM), whereas apparently a different proton symport accepted formate (0.13 mM). The lactate system was inducible and was subject to glucose repression. Undissociated lactic acid entered the cells by simple diffusion. The permeability of the plasma membrane for undissociated lactic acid increased exponentially with pH, and the diffusion constant increased 40-fold when the pH was increased from 3.0 to 6.0.


d-Fructose Modification Enhanced Internalization of Mixed Micelles in Breast Cancer Cells via GLUT5 Transporters.
d-Fructose modified poly(ε-caprolactone)-polyethylene glycol (PCL-PEG-Fru) diblock amphiphile is synthesized via Cu(I)-catalyzed click chemistry, which self-assembles with D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) into PCL-PEG-Fru/TPGS mixed micelles (PPF MM). It has been proven that glucose transporter (GLUT)5 is overexpressed in MCF-7 cells other than L929 cells. In this study, PPF MM exhibit a significantly higher uptake efficiency than fructose-free PCL-PEG-N3 /TPGS mixed micelles in both 2D MCF-7 cells and 3D tumor spheroids. Also, the presence of free d-fructose competitively inhibits the internalization of PPF MM in MCF-7 cells other than L929 cells. PPF MM show selective tumor accumulation in MCF-7 breast tumor bearing mice xenografts. Taken together, PPF MM represent a promising nanoscale carrier system to achieve GLUT5-mediated cell specific delivery in cancer therapy.


Low-temperature electron paramagnetic resonance study of the ferricytochrome c-cardiolipin complex.
The electron paramagnetic resonance spectrum of the ferricytochrome c complex with cardiolipin was observed at temperatures below 20 K. For the low-spin iron(III) heme system complexed with the negatively charged lipid, the tetragonal and rhombic ligand field parameters (delta/lambda = 3.58, V/lambda = 1.82) differ significantly from those (delta/lambda = 2.53, V/lambda = 1.49) of the free ferricytochrome c sample. The g values of the complex (gx = 1.54 +/- 0.02, gy = 2.26 +/- 0.01, gz = 3.02 +/- 0.01) are compared to the values for free ferricytochrome c (gx = 1.25 +/- 0.02, gy = 2.25 +/- 0.01, gz = 3.04 +/- 0.01). Spectral alterations are interpreted in terms of the ligand field changes induced within the heme group by association with the negatively charged phosphoglyceride.


From monologue to dialogue: a transition in psychoanalytic practice.
During the latter part of the twentieth century, psychoanalysts of various stripes espoused the move from free association and neutrality to various forms of intersubjectivity and dialogue. This shift is studied from the vantage point of conversational rules in terms of the shift from monologue to dialogue, using the concepts of semantics, syntax, and pragmatics. Viewing the data of analysis in this manner offers a means of evaluating the contributions of both monologue and dialogue to our understanding of the conduct of an analysis and the kind of information that can be expected to emerge. Exclusive devotion to either stance, it is argued, renders less understanding than would emerge from a balanced use of both.


A protein encoded by din1, a dark-inducible and senescence-associated gene of radish, can be imported by isolated chloroplasts and has sequence similarity to sulfide dehydrogenase and other small stress proteins.
In an attempt to isolate cDNA clones for dark-inducible chloroplast proteins, we screened a cDNA library which was prepared from radish cotyledons by a two-step method. The source plants were grown under continuous light for 14 d and kept in darkness for 24 h. One of the selected clones, S2D12, corresponded to the din1 gene which we previously reported as a dark-inducible, senescence-associated gene [Azumi and Watanabe (1991) Plant Physiol. 95:577]. A 22 kDa polypeptide was produced from the cDNA in an in vitro expression system in the presence of [35S]methionine. This polypeptide was capable of being imported by isolated chloroplasts, processed to a smaller mature form and localized in the stromal fraction. As the amino acid sequence of the putative mature protein has no homology to any known chloroplast protein, din1 was suggested to be the first gene for a chloroplast protein which is negatively controlled by light. The putative mature protein has similarity to sulfide dehydrogenase from Wolinella succinogenes and other small stress proteins; glpE and pspE from Escherichia coli and hsp67B2 from Drosophila melanogaster.


Habit in Personality and Social Psychology.
Habits are largely absent from modern social and personality psychology. This is due to outdated perspectives that placed habits in conflict with goals. In modern theorizing, habits are represented in memory as implicit context-response associations, and they guide responding in conjunction with goals. Habits thus have important implications for our field. Emerging research shows that habits are an important mechanism by which people self-regulate and achieve long-term goals. Also, habits change through specific interventions, such as changes in context cues. I speculate that understanding of habits also holds promise for reducing intergroup discrimination and for understanding lay theories of the causes for action. In short, by recognizing habit, the field gains understanding of a central mechanism by which actions persist in daily life.


Effects of Land Cover on the Movement of Frugivorous Birds in a Heterogeneous Landscape.
Movement is a key spatiotemporal process that enables interactions between animals and other elements of nature. The understanding of animal trajectories and the mechanisms that influence them at the landscape level can yield insight into ecological processes and potential solutions to specific ecological problems. Based upon optimal foraging models and empirical evidence, we hypothesized that movement by thrushes is highly tortuous (low average movement speeds and homogeneous distribution of turning angles) inside forests, moderately tortuous in urban areas, which present intermediary levels of resources, and minimally tortuous (high movement speeds and turning angles next to 0 radians) in open matrix types (e.g., crops and pasture). We used data on the trajectories of two common thrush species (Turdus rufiventris and Turdus leucomelas) collected by radio telemetry in a fragmented region in Brazil. Using a maximum likelihood model selection approach we fit four probability distribution models to average speed data, considering short-tailed, long-tailed, and scale-free distributions (to represent different regimes of movement variation), and one distribution to relative angle data. Models included land cover type and distance from forest-matrix edges as explanatory variables. Speed was greater farther away from forest edges and increased faster inside forest habitat compared to urban and open matrices. However, turning angle was not influenced by land cover. Thrushes presented a very tortuous trajectory, with many displacements followed by turns near 180 degrees. Thrush trajectories resembled habitat and edge dependent, tortuous random walks, with a well-defined movement scale inside each land cover type. Although thrushes are habitat generalists, they showed a greater preference for forest edges, and thus may be considered edge specialists. Our results reinforce the importance of studying animal movement patterns in order to understand ecological processes such as seed dispersal in fragmented areas, where the percentage of remaining habitat is dwindling.


Cystic fibrosis mortality and survival in the UK: 1947-2003.
Data up to 1995 on the survival of 3-yr cohorts of patients with cystic fibrosis (CF) born in the UK in the period 1968-1992 have previously been published. The present study reports survival data up to the end of 2003 together with a 2003 population estimate. All subjects with CF born in the UK in the period 1968-1992 were identified up to 1997 by active enquiry through recognised CF clinics and other hospital consultants. Information from the death certification authorities up to the end of 2003 was added. Death certificates that could not be matched with UK Cystic Fibrosis Survey records were investigated and the data reconciled. The observed survival up to 2003 of CF patients born in 1978 was 55% for males and 49% for females. For 1988 and 1992 the data were 91 and 88%, and 97 and 96%, respectively. The estimated 2003 mid-year CF population was 8,284. The continuing improvement in survival of cystic fibrosis patients in successive cohorts means that the previous prediction of median survival of >50 yrs of age for individuals born in 2000 continues to look realistic, even in the absence of proven effective therapy aimed at correcting the basic cystic fibrosis defect.


Involving the cerebellum in cocaine-induced memory: pattern of cFos expression in mice trained to acquire conditioned preference for cocaine.
Because of its primary role in drug-seeking, consumption and addictive behaviour, there is a growing interest in identifying the neural circuits and molecular mechanisms underlying the formation, maintenance and retrieval of drug-related memories. Human studies, which focused on neuronal systems that store and control drug-conditioned memories, have found cerebellar activations during the retrieval of drug-associated cue memory. However, at the pre-clinical level, almost no attention has been paid to a possible role of the cerebellum in drug-related memories. In the present study, we ought to fill this gap by aiming to investigate the pattern of neuronal activation (as revealed by cFos expression) in different regions of the prefrontal cortex and cerebellum of mice trained to develop conditioned preference for an olfactory stimulus (CS+) paired with cocaine. Our results indicate that CS+ preference was directly associated with cFos expression in cells at the apical region of the granule cell layer of the cerebellar vermis; this relationship being more prominent in some specific lobules. Conversely, cFos+ immunostaining in other cerebellar regions seems to be unrelated to CS+ preference but to other aspects of the conditioning procedure. At the prefrontal cortex, cFos expression seemed to be related to cocaine administration rather than to its ability to establish conditioned preference. The present results suggest that as it has been observed in some clinical studies, the cerebellum might be an important and largely overlooked part of the neural circuits involved in generating, maintaining and/or retrieving drug memories.


Integration of genome-wide association studies (GWAS) and microbiome data highlights the impact of sulfate-reducing bacteria on Alzheimer's disease.
observational studies have indicated that gut microbiome dysbiosis was associated with Alzheimer's disease (ad). However, the results are largely inconsistent and it remains unknown whether the association is causal in nature. leveraging observational studies and genome-wide association studies (GWAS) on the gut microbiome in ad patients, we pooled the microbiome data (N = 1,109) to screen the microbiota significantly altered in ad patients and then conducted Mendelian randomisation (MR) study to determine the causal associations between altered microbiota (N = 18,340) and ad using two different ad GWAS datasets (N = 63,926 and N = 472,868) using the inverse variance-weighted (IVW) method. the combined effect sizes from observational studies showed that 8 phyla, 18 classes, 22 orders, 37 families, 78 genera and 109 species significantly changed in ad patients. Using the MR analysis, we found that two classes, one order, one family and one genus were suggestively associated with ad consistently in two different GWAS datasets. Both observational studies and MR analysis simultaneously showed that Desulfovibrionales (order) and Desulfovibrionaceae (family), which were mainly implicated in dissimilatory sulfate reduction, were significantly associated with an elevated risk of ad. our findings demonstrated that the abundance of sulfate-reducing bacteria was increased in ad patients, which was causally linked to an increased risk of ad. Further efforts are warranted to clarify the underlying mechanisms, which will provide new insight into the prevention and treatment of ad.


Azathioprine treatment of chronic pulmonary sarcoidosis.
The object of this study was to evaluate the effectiveness of the immuno-suppressor Azathioprine (AZ) on chronic and severe pulmonary sarcoidosis, with a persistent activity resistant to prolonged corticotherapy. The study was done on 10 patients (4 women, 6 men) afflicted by an histologically proven and chronic sarcoidosis, resistant to steroid treatment. The treatment consisted of a daily oral intake of 150 mg of AZ for six months. Its effectiveness was evaluated before and after treatment, in comparison with a control group and a steroid-treated group of sarcoid patients. Serologic and alveolar functional and immuno-biologic tests were performed in 8 cases according to the activity criteria defined at the IXth International Congress on sarcoidosis. No clinical or hematological side effects were observed; a clear and prolonged radiological and clinical amelioration was observed in 7 out of 10 cases and in 3 cases a restoration of sensibility to the tuberculin skin test; in the 8 cases a significant improvement (p less than 0.01) was noted after the sixth month of treatment only in the alveolar fluid in the following parameters: ACE, all the proteins studied and the percentage of lymphocytes.