[Headache as initial symptom of schizophrenic disease].
Initial schizophrenia was observed in 15 out of 93 out-patients being treated for cephalea in a Regional Neuropsychiatrical Department. Certain abnormal phenomena in the field of consciousness and body sensations are typical of coenasthetic schizophrenia, with vital asthenia and vegetative symptoms. Cephaleas and head dysaesthesias are reported. There is no doubt that coenaesthetic schizophrenia has many points in common with latent schizophrenia; on the other hand it is also closely linked to hypochondriac depression, the syndrome of endogenous juvenile failure, certain latent depressions, hypochondriac euphoria, vegetative and endoreactive dysthmia and pseudoneurotic schizophrenia. Personal studies of stress responses in schizophrenia, and pneumoencephalographic examinations and EEG data in the active stage suggest diencephalic alteration. For diagnostic and initially therapeutic purposes, every patient with cephalea should be examined thoroughly by the psychiatrist; in this way the number of schizophrenias identified and treated will be considerably increased.


Is Br2 hydration hydrophobic?
The spectroscopic properties of bromine in aqueous systems suggest it can behave as either hydrophilic or hydrophobic solute. In small water clusters, the halogen bond and the hydrogen-halogen interaction are responsible for its specific way of binding. In water hydrates, it is efficiently hosted by two different cages forming the crystal structure and it has been frequently assumed that there is little or no interaction between the guest and the host. Bromine in liquid solution poses a challenging question due to its non-negligible solubility and the large blue shift measured in its absorption spectra. Using a refined semi-empirical force field, PM3-PIF, we performed a Born-Oppenheimer molecular dynamics study of bromine in liquid water. Here we present a detailed study in which we retrieved the most representative hydration structures in terms of the most frequent positions around bromine and the most common water orientations. Albeit being an approximate description of the total hydration phenomenon, it captures the contribution of the leading molecular interactions in form of the recurrent structures. Our findings confirm that the spectroscopic signature is mainly caused by the closest neighbors. The dynamics of the whole first hydration shell strongly suggests that the external molecules in that structure effectively isolate the bulk from the presence of bromine. The solvation structure fluctuates from a hydrophilic to a hydrophobic-like environment along the studied trajectory.


The preparation of porcine (Tyr-A14-2H) insulin and its characterization by mass spectrometry.
The title compound was prepared by catalytic deiodination of (Tyr-A14-3-I) insulin with deuterium gas. Under special conditions (large excess of PdO in CH3OD/D2O at pH 9.2) developed to minimize problems due to poisoning of the catalyst, deuterated insulin was produced in yields of about 35% after purification by reversed phase HPLC. For analysis, the deuterated insulin was digested with V8 protease and was shown by mass spectrometry to have incorporated deuterium to an extent of 96.6 atom %, exclusively in a pentapeptide containing Tyr A14. The title compound should prove useful to those workers studying insulin by mass spectrometry, and use of the method with tritium gas in place of deuterium should permit the preparation of a specifically labelled radioactive insulin analogue which behaves identically to the natural hormone.


Composition, biophysical properties, and morphometry of plasma membranes in pulmonary interstitial edema.
We evaluated the changes in plasma membrane composition, biophysical properties, and morphology of pulmonary endothelial cells in anesthetized rabbits receiving 0.5 ml. kg(-1). min(-1) saline infusion for 180 min, causing mild interstitial edema. Plasma membrane fractions were obtained from lung homogenates with gradient centrifugation, allowing a sixfold enrichment in caveolin-1. In edematous lungs, cholesterol content and phospholipidic phosphorus increased by 15 and 40%, respectively. These data correlated with morphometric analysis of lungs fixed in situ by vascular perfusion with 2.5% glutaraldehyde, suggesting a relative increase in surface of luminal to interstitial front of the capillary endothelial cells, due to a convoluted luminal profile. In edematous lungs, the fraction of double-bound fatty acids increased in membrane lipids; moreover, the phosphatidylcholine/phosphatidylethanolamine and the cholesterol/phospholipid ratios decreased. These changes were consistent with the increase in fluorescence anisotropy of plasma membrane, indicating an increase in its fluidity. Data suggest that mechanical stimuli elicited by a modest (approximately 4%) increase in extravascular water cause marked changes in plasma membranes that may be of relevance in signal transduction and endothelial cell activation.


Intraoperative pulmonary oedema in a child following systemic absorption of phenylephrine eyedrops.
Ophthalmic surgeons often apply phenylephrine topically to effect pupillary dilatation. We describe a paediatric patient in whom cardiac arrhythmias, severe hypertension and pulmonary oedema occurred following intraoperative ocular phenylephrine administration. We believe that systemic absorption of the drug was responsible and discuss ways in which this might be reduced when ocular phenylephrine is used in this context.


Automated external defibrillators and the link to first responder systems.
Automated external defibrillators are a very effective treatment to convert ventricular fibrillation (VF) in out-of-hospital cardiac arrest. The purpose of this paper is to review recent publications related to automated external defibrillators (AEDs). Much of the recent research focus on ways to utilize publicly available AEDs included in different national/regional registers. More and more research present positive associations between engaging volunteers to increase the use of AEDs. There are only a few recent studies focusing on professional first responders such as fire fighters/police with mixed results. The use of unmanned aerial vehicles (drones) lacks clinical data and is therefore difficult to evaluate. On-site use of AED shows high survival rates but suffers from low incidence of out-of-hospital cardiac arrest (OHCA). The use of public AEDs in OHCA are still low. Systems focusing on engaging volunteers in the cardiac arrest response have shown to be associated with higher AED usage. Dispatching drones equipped with AEDs is promising, but research lacks clinical data. On-site defibrillation is associated with high survival rates but is not available for most cardiac arrests.


Glia as architects of central nervous system formation and function.
Glia constitute roughly half of the cells of the central nervous system (CNS) but were long-considered to be static bystanders to its formation and function. Here we provide an overview of how the diverse and dynamic functions of glial cells orchestrate essentially all aspects of nervous system formation and function. Radial glia, astrocytes, oligodendrocyte progenitor cells, oligodendrocytes, and microglia each influence nervous system development, from neuronal birth, migration, axon specification, and growth through circuit assembly and synaptogenesis. As neural circuits mature, distinct glia fulfill key roles in synaptic communication, plasticity, homeostasis, and network-level activity through dynamic monitoring and alteration of CNS structure and function. Continued elucidation of glial cell biology, and the dynamic interactions of neurons and glia, will enrich our understanding of nervous system formation, health, and function.


Relationship between the extent of lipid substitution on poly(L-lysine) and the DNA delivery efficiency.
Poly(L-lysine) (PLL) is a commonly used polymer for nonviral gene delivery. However, the polymer exhibits significant toxicity and is not very effective for transgene expression. To enhance the gene delivery efficiency of the polymer, we imparted an amphiphilic property to PLL by substituting approximately 10% of epsilon-NH2 with several endogenous lipids of variable chain lengths (lipid carbon chain ranging from 8 to 18). Lipid-modified PLL with high molecular weight (approximately 25 vs 4 kDa) was found to be more effective in delivering plasmid DNA intracellularly in clinically relevant bone marrow stromal cells (BMSC). For lipid-substituted 25 kDa PLL, a correlation between the extent of lipid substitution and the plasmid DNA delivery efficiency was obtained. Additionally, transgene expression by BMSC significantly increased (20-25%) when amphiphilic PLLs were used for plasmid delivery as compared to native PLL and the commercial transfection agent Lipofectamine-2000. The transfection efficiency of the polymers was positively correlated with the extent of lipid substitution. The amphiphilic polymers were able to modify the cells up to 7 days after transfection, after which the expression was decreased to background levels within 1 week. We conclude that lipid-substituted PLL can be used effectively as a nonviral carrier for DNA, and the extent of lipid substitution was an important determinant of gene delivery.


Investigation of major genetic polymorphisms in the Renin-Angiotensin-aldosterone system in subjects with young-onset hypertension selected by a targeted-screening system at university.
Although polymorphisms in renin-angiotensin-aldosterone (RAA) system genes for angiotensinogen (AGT M235T), angiotensin-converting enzyme (ACE I/D), angiotensin II type 1 receptor (AT1 A/C1166), and aldosterone synthase (CYP11B2-344T/C) have been major targets for genetic investigation in association with essential hypertension (EH), the influence of these genetic factors is still to be determined. Because patients with young-onset EH are thought to possess a stronger genetic background than EH patients who show elevated BP relatively late in life, the targeted screening of hypertensive students in Tohoku University was completed for the selection of subjects for genetic investigation. Out of 16,434 students (12,794 males and 3,670 females) younger than 30, 22 students showed a high blood pressure (BP) (systolic and diastolic BP of 140 and/or 90 mmHg or greater, respectively, on two occasions and more than 135 and/or 85 mmHg, respectively, at a third measurement during casual BP measurements at the Tohoku University Health Center. These 22 students were asked to measure their BP at home (HBP). Six of the students had a systolic HBP of more than 135 mmHg and/or a diastolic HBP of more than 85 mmHg, and these students subsequently received medical examinations at Tohoku University Hospital and were diagnosed with EH. Genotyping for the four major genetic polymorphisms mentioned above was performed on the six students with EH and on 12 of the remaining 16 students whose HBP was within the normal range (white coat hypertension: WCH). Neither the EH nor the WCH students showed a different distribution of genotypes and allelic frequencies, compared to those found in the general Japanese population. Hence, the present study suggests that none of the major genetic polymorphisms in the RAA system strongly influence the onset of EH.


[Diversity of oviposition containers and buildings where Aedes albopictus and Aedes aegypti can be found].
To assess the diversity of oviposition containers and buildings where females of Aedes albopictus and Aedes aegypti can be found. A study was carried out in the city of Rio de Janeiro, Southern Brazil, between 2002 and 2003. Larvae in different types of buildings were investigated, and immature forms found were then sent to the laboratory for identification. The larval frequency for both mosquitoes was estimated in the oviposition containers available. The Breteau index and the building infestation index were calculated and differences were tested using the Chi-square test. The types of buildings that were positive for Aedes albopictus and Aedes aegypti were: dwellings (83.9%); churches, schools, clubs (6.8%); vacant land (6.4%); and businesses (2.8%). Of 9,153 larvae collected, 12.0% were Aedes albopictus and 88.0% were Aedes aegypti. Aedes albopictus were mostly found in drains (25.4%); cans, bottles, empty bottles (23.9%); and plant vases (16.2%). Aedes aegypti was much more frequently found than Aedes albopictus (chi(2)=145.067; p<0.001). Both species were significantly more frequent in artificial than in natural oviposition containers (chi(2)=31.46; p<0.001). The building infestation index and Breteau index for Aedes albopictus were 0.3% and 0.28% in 2002 and 0.4% and 0.5 in 2003, respectively. For Aedes aegypti, they were 1.0%, 1.16 in 2002 and 3.5% and 4.35 in 2003, respectively. The present study assessed the frequencies of Aedes albopictus and Aedes aegypti females in various types of oviposition containers and types of buildings. The abundant availability of artificial containers in dwellings, associated with the capacity of Ae. albopictus to be also found in natural oviposition containers, has greatly contributed for their gradual adaptation to human environment.


Plasma immunoreactive beta-endorphin, ACTH and cortisol concentrations in mothers and their neonates immediately after delivery--their relationship to the duration of labor.
In 29 cases of vaginal delivery with normal outcome and 4 cases of cesarean section, the concentrations of beta-endorphin, ACTH and cortisol were determined in maternal venous and umbilical venous plasma immediately postpartum. According to duration of labor and mode of delivery the cases examined were classified into three groups: Group A (18 cases) = vaginal delivery of less than 10 hours' duration, Group B (11 cases) = vaginal delivery of more than 10 hours' duration of labor, Group C (4 cases) = cesarean section under general anesthesia. With the exception of one, the deliveries took place at term. The 33 neonates were in a very good clinical state 5 minutes after parturition (11 Saling points as median value). For measurement of the hormone concentrations radioimmunoassays were used. In Group a the mean beta-endorphin concentration in maternal plasma amounted to 150.9 +/- 16.3 pg/ml, that in neonatal plasma to 239.2 +/- 23.5 pg/ml (means +/- SEM). In Group B plasma beta-endorphin, both maternal and neonatal, was slightly higher than in Group A: 153.0 +/- 12.0 pg/ml (maternal) and 260.9 +/- 37.1 pg/ml (neonatal). The differences between maternal and neonatal beta-endorphin levels were statistically significant: Group A p less than 0.01, Group B p less than 0.05; chi 2-test. The mean ACTH concentrations in the plasma of the newborn infants were also found to be considerably higher compared with those in the plasma of their mothers: Group A 78.2 +/- 16.5 pg/ml (maternal) and 98.0 +/- 23.3 pg/ml (neonatal); Group B 98.0 +/- 20.1 pg/ml (maternal) and 165.8 +/- 39.6 pg/ml (neonatal).(ABSTRACT TRUNCATED AT 250 WORDS)


Voltammetric determination of homocysteine using multiwall carbon nanotube paste electrode in the presence of chlorpromazine as a mediator.
We propose chlorpromazine (CHP) as a new mediator for the rapid, sensitive, and highly selective voltammetric determination of homocysteine (Hcy) using multiwall carbon nanotube paste electrode (MWCNTPE). The experimental results showed that the carbon nanotube paste electrode has a highly electrocatalytic activity for the oxidation of Hcy in the presence of CHP as a mediator. Cyclic voltammetry, double potential step chronoamperometry, and square wave voltammetry (SWV) are used to investigate the suitability of CHP at the surface of MWCNTPE as a mediator for the electrocatalytic oxidation of Hcy in aqueous solutions. The kinetic parameters of the system, including electron transfer coefficient, and catalytic rate constant were also determined using the electrochemical approaches. In addition, SWV was used for quantitative analysis. SWV showed wide linear dynamic range (0.1-210.0 μM Hcy) with a detection limit of 0.08 μM Hcy. Finally, this method was also examined as a selective, simple, and precise electrochemical sensor for the determination of Hcy in real samples.


Integrated primary care behavioural health in a regional network of FQHC agencies during COVID-19.
(1) Examine the ability to sustain integrated primary care behavioural health (eg, colocation, communication and coordination) in 40 community health centres, during the COVID-19 pandemic and (2) review adaptations and challenges to provide integrated behavioural health via telehealth. This qualitative investigation assessed 55 behavioural health consultants (BHCs), via semistructured interviews, spanning 40 practice sites and 10 organisations, on their adjustment to telehealth delivery, modified practice workflows and challenges of maintaining integration while displaced by the pandemic. Assessment of the level of integrated care was also conducted with available semistructured tools. The results highlight rapid service adjustment, positive patient and provider satisfaction, increased but lowered ratings of remote BHC integration and collaboration with the primary care teams and reduced behavioural health screening, compared with prepandemic levels. This investigation also highlights the co-occurring importance of racial disparities and injustice in patient care. In several settings, BHCs had a significant support role for staff self-care. The COVID-19 pandemic, and its subsequent shelter-in-place mandates and telehealth care provision, has altered standard integrated behavioural health practice, yet harnessed the accessible, generalist and team-based spirit to meet the increasing behavioural health needs in this community.


Silencing of miR-19a-3p enhances osteosarcoma cells chemosensitivity by elevating the expression of tumor suppressor PTEN.
MicroRNAs (miRNAs/miRs) are small non-coding RNAs, which serve important roles in tumor progression. The present study analyzed the role of miR-19a-3p in the chemosensitivity of osteosarcoma (OS) cells. Overexpression of miR-19a-3p was observed in OS cells and a cisplatin-resistant MG63 cell line was subsequently constructed. It was observed that miR-19a-3p inhibitor transfection suppressed cell proliferation and decreased the expression of Ki67 and PCNA compared with the cisplatin treatment group. miR-19a-3p inhibitor transfection also promoted apoptotic rate, increased the expression of Bcl-2 associated X, apoptosis regulator (Bax) and markedly decreased the expression of Bcl-2 compared with the cisplatin treatment group. These results elucidated that silencing of miR-19a-3p enhanced chemosensitivity of OS cells to Cisplatin, through suppressing cell proliferation and promoting cell apoptosis during treatment with Cisplatin. Bioinformatics study and luciferase reporter assays indicated that PTEN was a target of miR-19a-3p, and western blotting demonstrated that PTEN expression was negatively regulated by miR-19a-3p in OS cells. In addition, overexpression of PTEN decreased cell proliferation, but increased apoptotic rate compared with the cisplatin treatment group. It was observed that inhibition of PTEN by BpV(HOpic) upregulated cell proliferation and downregulated apoptotic rate compared with the Cisplatin-treated miR-19a-3p inhibitor group, indicating that inhibition of PTEN expression counteracted the effect of the miR-19a-3p inhibitor on the regulation of chemosensitivity in OS cells. Taken together, overexpression of miR-19a-3p was observed in OS cell lines and that downregulation of miR-19a-3p enhanced the chemosensitivity of OS cells to Cisplatin, by elevating the expression of the tumor suppressor, PTEN.


Counselling a patient with chronic illness before pregnancy.
As the reproductive age of women increases, women of reproductive age are exposed to more diseases and medications that are potentially related to adverse pregnancy outcomes. The approach to primary prevention of such outcomes is discussed. By minimizing the risks related to the diseases and the medications before conception, the best control of the medical condition and optimized pharmacotherapy is achieved when conception eventually occurs.


[Distribution characteristics of soil organic carbon, nitrogen and phosphorus in densely populated village landscapes of different hilly regions of China].
Based on high spatial resolution remote sensing map (1 m) and sampling with a stratified design on different site types, the effects of fine-scale land use patterns in villages on top soil (0-30 cm) organic carbon (OC), total nitrogen (TN) and total phosphorus (TP) within and across the densely populated hilly landscapes, i. e., Sichuan Hilly Region (SIHR; Jintang County, Sichuan Province), Subtropical Hilly Region (SUHR; Yiyang County, Hunan Province), and Tropical Hilly Region (THR; Dianbai County, Guangdong Province), were investigated. The results showed that soil OC density was decreased in the order of SUHR (2.72 +/- 0.76 kg x m(-2)) > THR (2.65 +/- 0.73 kg x m(-2)) > SIHR (2.15 +/- 0.57 kg x m(-2)), TN density was in the order of SUHR (0.28 +/- 0.06 kg x m(-2)) > SIHR (0.27 +/- 0.06 kg x m(-2) > THR (0.21 +/- 0.06 kg x m(-2)), and TP density was in the order of SIHR (0.19 +/- 0.04 kg x m(-2)) > SUHR (0.11 +/- 0.03 kg x m(-2)) > THR (0.08 +/- 0.04 kg x m(-2)). The fine-scale landscape units (ecotopes) with the highest soil OC, TN and/or TP stocks were rainfed annual crops in SIHR, paddy rice in SUHR, and open canopy trees and brush in THR, respectively. In all hilly regions, paddy and forest land use classes had the highest soil OC and TN density, while mined areas had the lowest soil OC and TN density, with the distribution of TP density showing a more complicated pattern than that of OC and TN. Ecotope level analysis could reflect the soil organic carbon, nitrogen and phosphorus distribution in densely populated village landscape of hilly regions more comprehensively than land use or land cover analysis.


Oral health survey of the military personnel deployed to the southernmost provinces of Thailand.
Dental problems are some of the major health problems of deployed miilitaly personnel. There have been no systematically reports of oral health information survey among the deployed military personnel in Thailand. The present study was to determine the oral health problems of the deployed military personnel and effects on personnel fitness. A cross-sectional study and a cluster sampling were conducted during April 2011 and March 2013. The Royal Thai Army (RTA) personnel 12 out of21 task forces in southern most provinces were invited to participate in the study. A standardized questionnaire was used. In total, 2,884 RTA deployed personnel voluntarily participated and completed the questionnaire infonnrmation. Their mean age was 27.8 +/- 9.4 years old. Fifty percent admitted that they had oral problems during the past six months and the most common ones were toothache/hypersensitivity (32.4%), and dental caries (21.5%). The majority of the participants (60.7%) reported that they experienced oral health problems less than 3 times and 2.8% reported sick leave during deployment because of oral conditions. 64.4% reported that their oral problems affected their quality of life and disturbed their duties. A relatively high prevalence oforal health problems was reported by the deployed RTA personnel. The problems affected their quality of life and assigned duties. Most ofthe problems were neglected. In order to keep the RTApersonnel fit for deployment, an effective dental health program should be developed.


Insights from computational analysis: how does the SARS-CoV-2 Delta (B.1.617.2) variant hijack ACE2 more effectively?
The SARS-CoV-2 Delta (B.1.617.2) variant was identified in India in October 2020, and it has quickly become the mainstream strain with strong toxicity and spread, posing great challenges to epidemic control. However, the molecular mechanism of its powerful infectivity remains unclear. It is meaningful to investigate the process of Delta variant's receptor-binding domain (RBD) binding to angiotensin-converting enzyme 2 (ACE2). Here, we performed three repeated molecular dynamics simulations for each system to avoid accidents, and the alanine scanning combined with the interaction entropy (ASIE) method was utilized to evaluate the binding free energy. Through the detailed energy and conformational analysis, the binding mechanism of the Delta variant was illustrated. The results showed that the existence of L452R and T478K mutations can trigger the effective hijacking of ACE2 by the Delta variant through the following three ways: (i) these two mutations can significantly enhance the electrostatic energy of the system by the introduction of two positively charged amino acids (Arg and Lys), thereby increasing the binding affinity of RBD and ACE2, (ii) the Loops 1, 3, and 4 in the receptor-binding motif (RBM) of RBD form a tighter conformation under the dominance of the T478K mutation, allowing ACE2 to be captured more effectively than the wild-type system, and (iii) these conformational changes lead to a more stable hydrogen bond in the Delta variant, which further ensures the stability of the binding. In addition, to explore the effect of mutations on the antibody, the key residues contributing to the changes in the binding ability of RBD in the Delta variant with the existing 42 neutralizing monoclonal antibodies (mAbs) have been preliminarily evaluated. The present study reveals the molecular mechanism for the increased infectivity of SARS-CoV-2 caused by mutations, and the key sites that cause antigenic changes were screened. It provides important theoretical insights for the development of novel targeted RBD drugs and antibodies.


Observational study of therapeutic bronchoscopy in critical hypoxaemic ventilated patients with COVID-19 at Mediclinic Midstream Private Hospital in Pretoria, South Africa.
Flexible fibreoptic bronchoscopy (FFB) has been used for years as a diagnostic and therapeutic adjunct for the diagnosis of potential airway obstruction as a cause of acute respiratory failure or in the management of hypoxaemia ventilated patients. In these circumstances, it is useful to evaluate airway patency or airway damage and for the management of atelectasis. To evaluate the use of FFB as a rescue therapy in mechanically ventilated patients with severe hypoxaemic respiratory failure caused by COVID-19. We enrolled 14 patients with severe and laboratory confirmed COVID-19 who were admitted at Mediclinic Midstream Private Hospital intensive care unit in Pretoria, South Africa, in July 2020. FFB demonstrated the presence of extensive mucus plugging in 64% (n=9/14) of patients after an average of 7.7 days of mechanical ventilation. Oxygenation improved significantly in these patients following FFB despite profound procedural hypoxaemia. Patients with severe COVID-19 pneumonia who have persistent hypoxaemia despite the resolution of inflammatory parameters may respond to FFB with removal of mucus plugs. We propose consideration of an additional pathophysiological acute phenotype of respiratory failure, the mucus type (M-type).


Changes in hydraulic conductance of citrus trees following a reduction in wetted soil volume.
The effcct of the transition from fully to partially wetted soil voluine on transpiration rate and hydraulic conductance of mature citrus trees was examined in a 23-year-old, coninicrcial, sprinklerirrigated, Shanio u t i orange orchard. I rriga t i on frequency was determined by the rate of water loss from the soil, a s measured by neutron probes. The hydraulic conductance of tlic tree was coniputed from the rclationship between sap flow i n the trunk and leaf water potential. The diurnal valucs of leaf water potential and sap flow shifted towards lower levels as tlie water stored in the root zone was depleted. In the fully wetted soil volume the tree hydraulic conductance remained constant throughout the irrigation period, from June to Novcniber. However, partial wetting of the soil volume (40%) caused a reduction in the hydraulic conductance of the tree. Tlie decreased hydraulic conductance is attributed to tlie permanent interruption of water transport in part of tlie root system. Tlie rcsults of tlie experiment suggest that despite tlie increase of irrigation frequency, partial wetting intensifies water stress in tlie trees.


Aortic valve replacement with combined myocardial revascularisation.
Early and late outcome was studied in 630 patients who underwent aortic valve replacement between 1974 and 1982. Group 1 (506 patients) did not have important coronary artery disease, group 2 (69 patients) had coronary artery disease and underwent coronary artery bypass grafting, and group 3 (55 patients) had coronary artery disease but did not undergo myocardial revascularisation. Early mortality (within 30 days of operation) was significantly lower for group 1 (6%) than for group 2 (13%) and for group 3 (16%). Operative mortality in all three groups was lower in patients operated on more recently. The three year survival of patients in group 1 (83%) was significantly higher than that of patients in group 3 (62%) but not than that of patients in group 2 (76%). The findings of this study suggest that the presence of coronary artery disease increases the risk of aortic valve replacement whether or not coronary artery grafting is performed. Myocardial revascularisation, however, seems to return patients with aortic valve and coronary artery disease to a survival curve similar to that of patients with isolated aortic valve disease.


Spinal stenosis.
Degenerative spinal stenosis is the most common type of stenosis encountered, often presenting with neurogenic claudication. History and physical examination indicate its presence and radiologic imaging is used to demonstrate the spatial reduction in the lumbar canals. Nonoperative therapy can be effective while surgical decompression offers the most reliable and definitive therapeutic intervention.


Slug inhibition increases radiosensitivity of oral squamous cell carcinoma cells by upregulating PUMA.
As a new strategy, radio-gene therapy was widely used for the treatment of cancer patients in recent few years. Slug was involved in the radioresistance of various cancers and has been found to have an anti-apoptotic effect. This study aims to investigate whether the modulation of Slug expression by siRNA affects oral squamous cell carcinoma sensitivity to X-ray irradiation through upregulating PUMA. Two oral squamous cell carcinoma cell lines (HSC3 and HSC6) were transfected with small interfering RNA (siRNA) targeting Slug and subjected to radiotherapy in vitro. After transfection with Slug siRNA, both HSC3 and HSC6 cells showed relatively lower expression of Slug and higher expression of PUMA. The Slug siRNA transfected cells showed decreased survival and proliferation rates, an increased apoptosis rate and enhanced radiosensitivity to X-ray irradiation. Our results revealed that Slug siRNA transfection in combination with radiation increased the expression of PUMA, which contributed to radiosensitivity of oral squamous cell carcinoma cells. Thus, controlling the expression of Slug might contribute to enhance sensitivity of HSC3 and HSC6 cells toward X-ray irradiation in vitro by upregulating PUMA.


An Astrocytic Influence on Impaired Tonic Inhibition in Hippocampal CA1 Pyramidal Neurons in a Mouse Model of Rett Syndrome.
Rett syndrome (RTT) is a severe neurodevelopmental disease caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. Although altered interneuron development and function are clearly demonstrated in RTT mice, a particular mode of inhibition, tonic inhibition, has not been carefully examined. We report here that tonic inhibition is significantly reduced in pyramidal neurons in the CA1 region of the hippocampus in mice where Mecp2 is deleted either in all cells or specifically in astrocytes. Since no change is detected in the level of GABA receptors, such a reduction in tonic inhibition is likely a result of decreased ambient GABA level in the extracellular space. Consistent with this explanation, we observed increased expression of a GABA transporter, GABA transporter 3 (GAT3), in the hippocampus of the Mecp2 KO mice, as well as a corresponding increase of GAT3 current in hippocampal astrocytes. These phenotypes are relevant to RTT because pharmacological blockage of GAT3 can normalize tonic inhibition and intrinsic excitability in CA1 pyramidal neurons, and rescue the phenotype of increased network excitability in acute hippocampal slices from the Mecp2 KO mice. Finally, chronic administration of a GAT3 antagonist improved a composite symptom score and extended lifespan in the Mecp2 KO mice. Only male mice were used in this study. These results not only advance our understanding of RTT etiology by defining a new neuronal phenotype and revealing how it can be influenced by astrocytic alterations, but also reveal potential targets for intervention.SIGNIFICANCE STATEMENT Our study reports a novel phenotype of reduced tonic inhibition in hippocampal CA1 pyramidal neurons in the Rett syndrome mice, reveal a potential mechanism of increased GABA transporter expression/activity in the neighboring astrocytes, describe a disease-relevant consequence in hyperexcitability, and provide preliminary evidence that targeting this phenotype may slow down disease progression in Rett syndrome mice. These results help our understanding of the disease etiology and identify a new therapeutic target for treating Rett syndrome.


Investigation of cell wall proteins of C. sinensis leaves by combining cell wall proteomics and N-glycoproteomics.
C. sinensis is an important economic crop with fluoride over-accumulation in its leaves, which poses a serious threat to human health due to its leaf consumption as tea. Recently, our study has indicated that cell wall proteins (CWPs) probably play a vital role in fluoride accumulation/detoxification in C. sinensis. However, there has been a lack in CWP identification and characterization up to now. This study is aimed to characterize cell wall proteome of C. sinensis leaves and to develop more CWPs related to stress response. A strategy of combined cell wall proteomics and N-glycoproteomics was employed to investigate CWPs. CWPs were extracted by sequential salt buffers, while N-glycoproteins were enriched by hydrophilic interaction chromatography method using C. sinensis leaves as a material. Afterwards all the proteins were subjected to UPLC-MS/MS analysis. A total of 501 CWPs and 195 CWPs were identified respectively by cell wall proteomics and N-glycoproteomics profiling with 118 CWPs in common. Notably, N-glycoproteomics is a feasible method for CWP identification, and it can enhance CWP coverage. Among identified CWPs, proteins acting on cell wall polysaccharides constitute the largest functional class, most of which might be involved in cell wall structure remodeling. The second largest functional class mainly encompass various proteases related to CWP turnover and maturation. Oxidoreductases represent the third largest functional class, most of which (especially Class III peroxidases) participate in defense response. As expected, identified CWPs are mainly related to plant cell wall formation and defense response. This was the first large-scale investigation of CWPs in C. sinensis through cell wall proteomics and N-glycoproteomics. Our results not only provide a database for further research on CWPs, but also an insight into cell wall formation and defense response in C. sinensis.


Concise Review: MSC-Derived Exosomes for Cell-Free Therapy.
Mesenchymal stem cell transplantation is undergoing extensive evaluation as a cellular therapy in human clinical trials. Because MSCs are easily isolated and amenable to culture expansion in vitro there is a natural desire to test MSCs in many diverse clinical indications. This is exemplified by the rapidly expanding literature base that includes many in vivo animal models. More recently, MSC-derived extracellular vesicles (EVs), which include exosomes and microvesicles (MV), are being examined for their role in MSC-based cellular therapy. These vesicles are involved in cell-to-cell communication, cell signaling, and altering cell or tissue metabolism at short or long distances in the body. The exosomes and MVs can influence tissue responses to injury, infection, and disease. MSC-derived exosomes have a content that includes cytokines and growth factors, signaling lipids, mRNAs, and regulatory miRNAs. To the extent that MSC exosomes can be used for cell-free regenerative medicine, much will depend on the quality, reproducibility, and potency of their production, in the same manner that these parameters dictate the development of cell-based MSC therapies. However, the MSC exosome's contents are not static, but rather a product of the MSC tissue origin, its activities and the immediate intercellular neighbors of the MSCs. As such, the exosome content produced by MSCs appears to be altered when MSCs are cultured with tumor cells or in the in vivo tumor microenvironment. Therefore, careful attention to detail in producing MSC exosomes may provide a new therapeutic paradigm for cell-free MSC-based therapies with decreased risk. Stem Cells 2017;35:851-858.


Comparison of capillary zone electrophoresis and isotachophoresis determination of dimethindene enantiomers in pharmaceuticals using charged carboxyethyl-beta-cyclodextrin as a chiral selector.
Charged cyclodextrin-mediated capillary electrophoretic methods (capillary zone electrophoresis [CZE] and isotachophoresis [ITP]) in a hydrodynamically closed separation system with suppressed electroosmotic flow and UV absorbance photometric detection (for CZE) or conductivity detection (for ITP) were developed for a highly effective separation and quantitation of dimethindene enantiomers in various pharmaceutical formulations (solution, gel, capsules). Optimized electrolyte systems were based on low-mobility buffer constituents (epsilon-aminocaproic acid, beta-alanine, potassium acetate, acetic acid), negatively charged (at pH > 4.5) carboxyethyl-beta-cyclodextrin (CE-beta-CD), serving as chiral selector, and methylhydroxyethylcellulose, serving as an electroosmotic flow suppressor. Complete enantioseparations of dimethindene in the presence of low concentrations of CE-beta-CD (2.5 mg/ml in CZE, 6.0 mg/ml in ITP) clearly indicated a role of charge of this chiral selector in enantioresolution. It also outlined the potential of charged CD-derivatives as chiral selectors for various CE techniques. The proposed methods were successfully validated, appraising parameters of sensitivity, linearity, precision, accuracy/recovery, and robustness, and then, they were applied to pharmaceutical samples. Consistent results obtained by both CE methods indicate their usefulness for routine use.


The rotational axis of the tibia and relationship to the tibial torsion in varus osteoarthritic knee.
A transepicondylar axis is a useful reference for femoral component rotation and is demonstrated as a functional flexion-extension axis of a knee. Conversely, a rotational orientation of the tibial component was less clearly demonstrated and many anatomical landmarks were proposed. It has been reported that Asian people had more medial torsion of the tibia particularly with an osteoarthritic knee. The present study aims to address the relationship between the torsion variation of the tibia and the rotational axis of the tibia. Forty knees of 32 women (mean age of 73.3) with varus osteoarthritis underwent a preoperative CT images to identify a surgical epicondylar axis, an axis perpendicular to this line (femoral reference line), lines connecting between the PCL insertion and 3 reference point on the patellar tendon, an AP axis of the ankle and a tibial torsion angle. The mean value of the angle between the line connecting the PCL insertion and 3 different point of the patellar tendon including the medial border medial one-third and middle of the patellar tendon and the femoral reference line was -4.22, +4.37 and +8.47 degree, respectively. The mean of a tibial torsion angle was +16.51 degree. There were 6 cases having the femoral reference line rotated internally to the medial border of the patellar tendon and having less torsion angle (medial tibial torsion) with a mean of +13.78 degree. The femoral reference line in the Thai osteoarthritic knee is passed between medial edge of patellar tendon and medial 1/3 of patellar tendon. This line rotates more internally compared with the patellar tendon if the degree of medial tibial torsion is more severe. An excessive externally rotated tibial component when using the patellar tendon as guidance should be avoided in the knee presenting with medial tibial torsion.


Extracting forces from noisy dynamics in dusty plasmas.
Extracting environmental forces from noisy data is a common yet challenging task in complex physical systems. Machine learning (ML) represents a robust approach to this problem, yet is mostly tested on simulated data with known parameters. Here we use supervised ML to extract the electrostatic, dissipative, and stochastic forces acting on micron-sized charged particles levitated in an argon plasma (dusty plasma). By tracking the subpixel motion of particles in subsequent images, we successfully estimated these forces from their random motion. The experiments contained important sources of non-Gaussian noise, such as drift and pixel locking, representing a data mismatch from methods used to analyze simulated data with purely Gaussian noise. Our model was trained on simulated particle trajectories that included all of these artifacts, and used more than 100 dynamical and statistical features, resulting in a prediction with 50% better accuracy than conventional methods. Finally, in systems with two interacting particles, the model provided noncontact measurements of the particle charge and Debye length in the plasma environment.


Subclinical thyroid dysfunction and blood pressure: a community-based study.
Overt hypothyroidism and hyperthyroidism are associated with hypertension, but it is uncertain whether the same is true of subclinical hypothyroidism and hyperthyroidism. Cross-sectional study of 2033 participants (aged 17-89 years) in the Busselton Thyroid Study who did not have a history of thyroid disease. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and the prevalence of hypertension (defined as SBP >or=140 mmHg, DBP >or=90 mmHg or on treatment for hypertension) in subjects with thyroid dysfunction and euthyroid subjects were compared using linear regression models. Subjects with treated hypertension (N = 299) were excluded from analyses of SBP and DBP but included in analyses of hypertension prevalence. Mean SBP, DBP and the prevalence of hypertension did not differ significantly between subjects with subclinical hypothyroidism (N = 105) and euthyroid subjects (N = 1859), nor did they differ between subjects with serum TSH concentrations in the upper reference range (2.0-4.0 mU/l; N = 418) and those with TSH concentrations in the lower reference range (0.4-2.0 mU/l; N = 1441). The prevalence of hypertension was higher in subjects with subclinical hyperthyroidism than euthyroid subjects (prevalence odds ratio 2.8, 95% confidence interval 1.3-6.0 adjusted for age, age(2) and sex), but this was based on a small number of subjects with subclinical hyperthyroidism (N = 35). Subclinical hypothyroidism is not associated with hypertension. The observed association between subclinical hyperthyroidism and hypertension requires confirmation in a larger sample.


Wire fixation techniques of the cervical facets.
The changes in the biomechanical responses of the cervical spine altered by multilevel laminectomy to various facet wiring techniques were evaluated. To determine the effectiveness of various proposed techniques of cervical facet wiring used to offer rigid internal fixation after multilevel laminectomy. Eight human cadaveric spine segments from C2-11 underwent combined flexion-compression loading. After testing intact and three-level laminectomy (C4-C6) preparations, two techniques of facet wiring fixation were evaluated in an identical manner. Force, displacement, and kinematics data at every level of the column were obtained. The mean stiffness of the intact column was significantly greater than the mean stiffness for laminectomized specimens. Individual facet wiring to the bone graft and through the spinous process below the laminectomy failed to restore stiffness to the laminectomized preparations, whereas the Luque rectangle method restored the stiffness to that found in the intact column. The increases in segmental and overall sagittal rotations resulting from multilevel laminectomy were not decreased significantly by the individual facet wiring technique, but the Luque rectangle technique demonstrated a reduction of sagittal rotations compared with laminectomy without fixation. The significant increases in total column flexibility and segmental flexural rotations after multilevel laminectomy were not corrected by techniques that depend on individual facet wires secured to an overlying strut, including wiring to the inferior intact segment. Crosslinking of the facet wire fixation above and below the laminectomized segments, as exemplified by the Luque rectangle technique, restored column stiffness and reduced segmental sagittal rotations.


Contrasting roles of IFN-gamma in murine models of autoimmune thyroid diseases.
Interferon-gamma (IFN-gamma), a prototypic proinflammatory cytokine produced by several different cell types, including the Th1 subset of CD4(+) T cells, plays an important role in inflammation and autoimmune diseases. This review focuses on the varied and often contrasting roles of IFN-gamma in three murine models of autoimmune thyroid disease, experimentally induced autoimmune thyroiditis, the model of iodine-induced spontaneous autoimmune thyroiditis in NOD.H-2h4 mice and several different murine models of Graves' disease.


Insulin modulation of Na/H antiport in rat red blood cells.
Red blood cells have been shown to possess specific insulin receptors, with characteristics similar to the receptors of typical target cells. The present work was carried out to study the modulation of amiloride sensitive Na/H antiport by insulin on rat red blood cells. The activity of the Na/H antiport was determined by a new technique which involves the measurement of the fluorescence of 2',7'-bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF) loaded rbc's as function of their intracellular pH (pHi). Our results show that the antiport in red blood cells displays the same behaviour as in other cells and it is inhibited by amiloride. Insulin stimulates the antiport with a dose-dependence similar to other typical insulin effects: a maximum at 10 nM and a smaller effect at higher and lower hormone concentrations. Insulin effect on the antiport was completely abolished by amiloride (0.1 mM) and significantly inhibited by ouabain (1 mM) showing, also in red blood cells, the strict dependence of the Na/H antiport on the functioning of the Na pump.


Emergent Properties of an Organic Semiconductor Driven by its Molecular Chirality.
Chiral molecules exist as pairs of nonsuperimposable mirror images; a fundamental symmetry property vastly underexplored in organic electronic devices. Here, we show that organic field-effect transistors (OFETs) made from the helically chiral molecule 1-aza[6]helicene can display up to an 80-fold difference in hole mobility, together with differences in thin-film photophysics and morphology, solely depending on whether a single handedness or a 1:1 mixture of left- and right-handed molecules is employed under analogous fabrication conditions. As the molecular properties of either mirror image isomer are identical, these changes must be a result of the different bulk packing induced by chiral composition. Such underlying structures are investigated using crystal structure prediction, a computational methodology rarely applied to molecular materials, and linked to the difference in charge transport. These results illustrate that chirality may be used as a key tuning parameter in future device applications.


Impact of body mass index on ovarian cancer survival varies by stage.
Research on the effect of body mass index (BMI) on ovarian cancer survival is inconsistent, but previous studies did not consider the possible impact of ascites, bowel obstruction, or cachexia, which commonly occur in late-stage disease. We evaluated the association of BMI, before and around the time of diagnosis, with overall and disease-specific survival in a cohort study of primary invasive epithelial ovarian cancers diagnosed from 2000 to 2013 in Kaiser Permanente Northern California (KPNC) (n=1184). Deaths were identified through December 2014, with a median follow-up of 37 months. Proportional hazards regression was used to estimate overall and ovarian cancer-specific mortality, accounting for prognostic variables including age at diagnosis, race, stage, grade, histology, comorbidities, treatment, post-treatment CA125 levels, ascites, and bowel obstruction. There was no evidence of an association between BMI and overall or ovarian cancer-specific survival. However, we found strong effect modification by stage (Pinteraction<0.01). Compared with normal prediagnosis BMI (18.5-24.9 kg m-2), for women who were obese before diagnosis (BMI⩾35 kg m-2) ovarian cancer-specific survival was lower among those diagnosed at stages I/II (hazard ratio (HR): 3.40; 95% confidence interval (CI): 1.16-9.99), but increased among those diagnosed with stage IV disease (HR: 0.58; 95% CI: 0.35-0.96). Associations were attenuated after excluding those diagnosed with cachexia (n=82) and further adjustment for ascites and bowel obstruction, with no evidence of effect modification by these factors. Associations of obesity with ovarian cancer survival may differ by stage, with decreased survival among those with localised disease and increased survival among those with late-stage disease. Stage-specific effects of obesity on survival suggest a tailored approach to improve prognosis may be appropriate.


The nature and extent of non-suicidal self-injury in a non-clinical sample of young adults.
This study aimed to examine the nature, extent and correlates of non-suicidal self injury (NSSI) in a non-clinical sample of young adults. Two hundred and eleven participants (18-30 years) completed self-report questionnaires assessing history of NSSI, emotional regulation, coping strategies, symptoms of psychopathology, and alcohol use. Of the sample, 43.6% reported engaging in NSSI; approximately 10% engaged in moderate/severe NSSI. Those that reported NSSI reported greater psychopathology, avoidant coping and alcohol use than those who did not self-injure. The extent of these differences was magnified as the severity of NSSI increased. These findings highlight the need to consider any form of NSSI, no matter how mild, as an indication of distress and ineffective coping.


Standard of Competence for Internists.
The ratification of law No. 29 regarding medical practices required the college to compile the standard of education and standard of competence for specialists.Recently, the College of Internal Medicine have compile the standard of competence for internal medicine specialists/internists, which will be the reference for all Educational Institution in compiling the Education Curriculum for Internal Medicine.The standard of competence for Internal Medicine Specialists/Internists is the minimum standard of competence that must be fulfilled by an internists. Therefore, with its presence, it is expected that participants of Program for Education and Professional Training of Internal Medicine Specialist/Internists who have already completed his/her education and training will have the equal quality of competence.Competence is a group of complex behavior, based on the components of knowledge, skill, and attitude that becomes the ability of a person in upholding his/her duty. In the Standard of Competence for Internal Medicine/Internists book, it is expected that an internist will acquire several competence, including integrated competence and clinical competence, in which clinical competence is further divided in to clinical competence of organ and system, special population, and special condition.


Pharmacokinetics and plasma protein binding of a single dose of clodronate disodium are similar for juvenile sheep and horses.
To determine the single-dose pharmacokinetics of clodronate disodium (CLO) in juvenile sheep and the plasma protein binding (PPB) of CLO in juvenile sheep and horses. 11 juvenile crossbred sheep (252 ± 6 days) for the pharmacokinetic study. Three juvenile crossbred sheep (281 ± 4 days) and 3 juvenile Quarter Horses (599 ± 25 days) for PPB analysis. CLO concentrations were determined using liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental analysis from plasma samples obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, and 72 hours after CLO administered IM at 0.6 mg/kg. PPB was determined using equine and ovine plasma in a single-use rapid equilibrium dialysis system. The mean and range for maximum plasma concentration (Cmax: 5,596; 2,396-8,613 ng/mL), time of maximal concentration (Tmax: 0.5; 0.5-1.0 h), and area under the curve (AUCall: 12,831; 7,590-17,593 h X ng/mL) were similar to those previously reported in horses. PPB in sheep and horses was moderate to high, with unbound fractions of 26.1 ± 5.1% in sheep and 18.7 ± 7.5% in horses, showing less than a 1.4-fold difference. The pharmacokinetic parameters and PPB of CLO in juvenile sheep were similar to those previously reported in horses. The results suggest that juvenile sheep can be utilized as an animal model for studying the potential risks and/or benefits of bisphosphonate use in juvenile horses.


Computational Model Based on Neural Network of Visual Cortex for Human Action Recognition.
In this paper, we propose a bioinspired model for human action recognition through modeling neural mechanisms of information processing in two visual cortical areas: the primary visual cortex (V1) and the middle temporal cortex (MT) dedicated to motion. This model, named V1-MT, is composed of V1 and MT models (layers) corresponding to their cortical areas, which are built with layered spiking neural networks (SNNs). Some neuron properties in V1 and MT, such as direction and speed selectivity, spatiotemporal inseparability, and center surround suppression, are integrated into SNNs. Based on speed and direction selectivity, V1 and MT models contain multiple SNN channels, each of which processes motion information in sequences with spatiotemporal tunings of neurons at a certain speed and different directions. Therefore, we propose two operations, input signal perceiving with 3-D Gabor filters and surround inhibition processing with 3-D differences of Gaussian functions, to perform this task according to the spatiotemporal inseparability and center surround suppression of neurons. Then, neurons are modeled with our simplified integrate-and-fire model and motion information is transformed into spike trains. Afterward, we define a new feature vector: a mean motion map computed from spike trains in all channels to represent human actions. Finally, a support vector machine is trained to classify actions represented by the feature vectors. We conducted extensive experiments on public action databases, and the results show that our model outperforms other bioinspired models and rivals the state-of-the-art approaches.


The Many Faces of Histidine Triad Nucleotide Binding Protein 1 (HINT1).
The histidine triad nucleotide binding protein 1 (HINT1) is a nucleoside phosphoramidase that has garnered interest due to its widespread expression and participation in a broad range of biological processes. Herein, we discuss the role of HINT1 as a regulator of several CNS functions, tumor suppressor, and mast cell activator via its interactions with multiple G-protein-coupled receptors and transcription factors. Importantly, altered HINT1 expression and mutation are connected to the progression of multiple disease states, including several neuropsychiatric disorders, peripheral neuropathy, and tumorigenesis. Additionally, due to its involvement in the activation of several clinically used phosphoramidate prodrugs, tremendous efforts have been made to better understand the interactions behind nucleoside binding and phosphoramidate hydrolysis by HINT1. We detail the substrate specificity and catalytic mechanism of HINT1 hydrolysis, while highlighting the structural biology behind these efforts. The aim of this review is to summarize the multitude of biological and pharmacological functions in which HINT1 participates while addressing the areas of need for future research.


Comparison of Caffeine and d-amphetamine in Cocaine-Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary Paraxanthine.
Due to indirect modulation of dopamine transmission, adenosine receptor antagonists may be useful in either treating cocaine use or improving disrupted cognitive-behavioral functions associated with chronic cocaine use. To compare and contrast the stimulant effects of adenosine antagonism to direct dopamine stimulation, we administered 150 mg and 300 mg caffeine, 20 mg amphetamine, and placebo to cocaine-dependent vs. healthy control subjects, matched on moderate caffeine use. Data were obtained on measures of cardiovascular effects, subjective drug effects (ARCI, VAS, DEQ), and a probabilistic reward-learning task sensitive to dopamine modulation. Levels of salivary caffeine and the primary caffeine metabolite paraxanthine were obtained on placebo and caffeine dosing days. Cardiovascular results revealed main effects of dose for diastolic blood pressure and heart rate; follow up tests showed that controls were most sensitive to 300 mg caffeine and 20 mg amphetamine; cocaine-dependent subjects were sensitive only to 300 mg caffeine. Subjective effects results revealed dose × time and dose × group interactions on the ARCI A, ARCI LSD, and VAS 'elated' scales; follow up tests did not show systematic differences between groups with regard to caffeine or d-amphetamine. Large between-group differences in salivary paraxanthine (but not salivary caffeine) levels were obtained under both caffeine doses. The cocaine-dependent group expressed significantly higher paraxanthine levels than controls under 150 mg and 3-4 fold greater levels under 300 mg at 90 min and 150 min post caffeine dose. However, these differences also covaried with cigarette smoking status (not balanced between groups), and nicotine smoking is known to alter caffeine/paraxanthine metabolism via cytochrome P450 enzymes. These preliminary data raise the possibility that adenosine antagonists may affect cocaine-dependent and non-dependent subjects differently. In conjunction with previous preclinical and human studies, the data suggest that adenosine modulating drugs may have value in the treatment of stimulant use disorders.


Long-term follow-up of newborns with persistent pulmonary hypertension.
Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome associated with high morbidity and mortality. Mechanical ventilation attempts to maintain a PaCO2 less than 30 torr and a pH greater than 7.5 until pulmonary hypertension resolves. To assess whether the disease or its therapy adversely affects neurodevelopmental or cardiorespiratory outcome, 11 infants diagnosed and treated for PPHN were evaluated at a mean age of 31 months. Nine had normal developmental quotients (DQs) and 2 had mildly delayed DQs. Eight children were entirely normal neurologically, 2 had slightly increased lower-extremity tone, and 1 had unilateral hypertonia. All cardiac exams, echocardiograms, and ECGs were normal. Four children had chronic lung disease requiring either daily or intermittent bronchodilator therapy; however, their activity levels were unaffected. These results suggest that subsequent normal development with little significant medical compromise may be expected in this group of critically ill infants.


An Effective Method of Continuous Production of Erythritol from Glycerol by Yarrowia lipolytica MK1.
This study demonstrates the potential applicability of the UV mutant Yarrowia lipolytica MK1 for the valorisation of glycerol and erythritol production in a chemostat culture. The aim of this research is to investigate the optimal C:N ratio in the feeding medium in order to enhance erythritol production. The highest erythritol concentration, at 113.1 g/L with a volumetric erythritol production rate of 1.1 g/(L·h) and a yield of 0.57 g/g, was obtained in the feeding medium with a C:N ratio of 80:1. Moreover, no residual glycerol was observed in the culture broth during cultivation. The chemical composition of the biomass was analysed. The contents of lysine and threonine in the biomass protein amino acid profile were higher than those required by the FAO/WHO for fodder yeast.


Changing epidemiology and management of deliberate self poisoning in Christchurch.
To review the epidemiology and emergency management of deliberate self poisoning by substance ingestion in Christchurch for 1992, with comparison to 1989. A retrospective analysis of case records was conducted for the year 1992, and compared with published data from 1989. There were 622 presentations (compared to 531 in 1989) of deliberate self poisoning by substance ingestion, representing 1.2% (cf 0.96%) of the total emergency department consultations. The female to male ratio was 1.5:1.0 (cf 2.1:1), with three quarters of patients being under the age of 35. The principle drugs ingested were antidepressants (24.4% cf 15.7%), hypnotic/anxiolytics 23.6% (benzodiazepines 18% cf 22.8% in 1989), paracetamol (16.9% cf 10.6%) and antipsychotics (16.1%, not reported 1989). Stomach emptying procedures were used in 27% of patients (cf 78%). Ipecacuanha was administered in 1% (cf 25%). Activated charcoal alone was used as the method of gastrointestinal decontamination in 46% (cf 0.4%). No attempt at decontamination was made for 27% of patients. Fifty nine percent (cf 66%) were admitted, 11% (cf 18%) to the intensive care unit. There were two inpatient deaths in both 1992 and 1989. Antidepressants have become the most frequently misused medication, and misuse of paracetamol has increased. However, self poisoning remains a phenomenon of low morbidity and mortality. Stomach emptying procedures are used much less frequently, making for substantial savings of time, resources and patient discomfort.


Certification program in antineoplastic drug preparation for pharmacy technicians and pharmacists.
A formal training program for technicians who prepare cytotoxic agents and pharmacists who check the doses is described. To handle an overwhelming workload in an oncology satellite pharmacy and to enable the pharmacists there to increase their clinical involvement, a program was developed to train technicians to prepare antineoplastic doses and pharmacists to check the technicians' work. The program consists of two days of classroom instruction, three weeks of hands-on training, and a written examination. In addition to handling and preparation of antineoplastic drugs, other topics related to oncology are covered to give the participants a better understanding of cancer and its treatment. The technicians must complete a refresher program annually. From 1991 to 1993, 15 pharmacists and 14 technicians and pharmacy students completed the program. The technicians have taken on additional responsibilities in the satellite pharmacy, including managing the inventory of oncology drugs. Implementation of a comprehensive cancer chemotherapy training class for technicians and pharmacists has benefited the pharmacy in terms of labor and inventory control.


Collision-induced dissociation of polyprotonated oligonucleotides produced by electrospray ionization.
The efficient production of polyprotonated oligonucleotides, studied at n < or = 19, occurs from water/propan-2-ol solutions over an ammonium acetate concentration range between 2.5 and 40 mm and a pH range from 5 to 11. Average charge-state levels observed were approximately half of those found in mass spectra of polyanionic oligonucleotides, reflecting differences in sites of ionization: heterocyclic bases for protonation and phosphodiester backbone for deprotonation. Collision-induced dissociation mass spectra show three principal reaction paths: (1) release of protonated bases, with abundances dictated largely by base proton affinity; (2) phosphodiester chain cleavage at C3'-O3' indicative of sequence in the 3'-->5' direction; and (3) chain cleavage concomitant with base loss giving furan-type ions indicative of sequence in the 5'-->3' direction, analogous to reactions of polyanionic oligonucleotides. Thymine residues undergo very little protonation, resulting in characteristic absence of phosphodiester cleavage on the 3' side of T sites, producing mass-ladder gaps representing dinucleotides.


Rising surface temperatures lead to more frequent and longer burrow retreats in males of the fiddler crab, Minuca pugnax.
The fiddler crab Minuca pugnax occupies thermally unstable mudflat habitats along the eastern United States coastline, where it uses behavioral thermoregulation, including burrow retreats, to manage body temperature (Tb). We explored the relationship between frequency of burrow use and environmental conditions, including burrow and surface temperatures, relative tidal height, and time of day, by twenty male M. pugnax in breeding areas around Flax Pond, New York, USA. We found a highly significant positive correlation between burrow use and surface temperature, with a clear shift to longer times underground above 32 °C degrees. We also experimentally heated live crabs in the laboratory and allowed them to retreat into cooled artificial burrows while continuously measuring Tb. Laboratory data on cooling times were compared to field observations of burrow retreat durations. The median burrow duration in the field of 2.74 min was enough time for our laboratory crabs to capture over 70% of the cooling potential of artificial burrows 10 or 15 °C below Tb. Because crab bodies in burrows experience exponential declines in Tb due to Newton's law of cooling, there are diminishing returns to remaining in a burrow, and many crabs probably leave before coming to equilibrium. For M. pugnax, burrow retreats reduce time spent feeding and courting, activities that only occur on the surface. Current concerns about the impacts of climate change on animals include whether compensatory mechanisms, like more frequent and longer burrow retreats, will come at the cost of other behaviors necessary for survival and reproduction.


Graves' disease in childhood: new epidemiological, pathophysiological and therapeutic insights.
In this review, the authors analyze the main epidemiological, pathophysiological, clinical and prognostic features of Graves' disease in childhood and provide some therapeutic insights.


To Systematically Evaluate and Analyze the Efficacy and Safety of Transcatheter Arterial Chemoembolization (TACE) in the Treatment of Primary Liver Cancer.
The efficacy and safety of transcatheter arterial chemoembolization (TACE) are systematically evaluated in the treatment of primary liver cancer, which provides a reference for clinical practice and more in-depth research. Cochrane Library, PubMed, EMbase, CBM, CNKI, VIP, and WanFang Data, supplemented by other searches, collected all randomized controlled trials (RCT) comparing TACE combined with TACE alone for HCC. The meta-analysis, after selecting the literature, extracting data, and evaluating the methodological quality of the included studies following the inclusion criteria, was performed using RevMan 5.1 software. There was statistical difference in 3-year survival rate of TACE combined with heat treatment for advanced hepatocellular carcinoma (OR = 1.72,95%CI (1.22,2.41), P=0.002, I2 = 0%, and Z = 3.12), total effective rate (OR = 1.91,95%CI (1.31,2.78), P=0.0008, I2 = 0%, and Z = 3.37), quality-of-life improvement rate (OR = 2.29,95%CI (1.62,3.23), P < 0.00001, I2 = 83%, and Z = 3.37), and complication rate (OR = 2.29,95%CI (1.62,3.23), P < 0.00001, I2 = 83%, and Z = 3.37). Compared with TACE alone, TACE combined with hyperthermia can significantly improve the survival rate and recent efficacy of patients, improve the quality of life, and have a trend to reduce the incidence of toxicity. However, its long-term efficacy and more comprehensive safety need to be verified by more sample and high-quality RCT.


Comparison of predicted with observed biokinetics of inhaled plutonium nitrate and gadolinium oxide in humans.
The absorption kinetics to blood of plutonium and gadolinium after inhalation as nitrate and oxide in humans and animals has been studied. For each material, values describing the time dependence of absorption were derived from the studies in animals and used with the ICRP human respiratory tract model to predict lung retention and cumulative amounts to blood for the volunteers inhaling the same materials. Comparison with the observed behaviour in the volunteers suggests that absorption of plutonium and gadolinium is reasonably species independent, and that data obtained from animal studies can be used to assess their biokinetic behaviour in humans.


Adaptive Neural Output Feedback Control for Nonstrict-Feedback Stochastic Nonlinear Systems With Unknown Backlash-Like Hysteresis and Unknown Control Directions.
This paper investigates the problem of output feedback adaptive stabilization for a class of nonstrict-feedback stochastic nonlinear systems with both unknown backlashlike hysteresis and unknown control directions. A new linear state transformation is applied to the original system, and then, control design for the new system becomes feasible. By combining the neural network's (NN's) parameterization, variable separation technique, and Nussbaum gain function method, an input-driven observer-based adaptive NN control scheme, which involves only one parameter to be updated, is developed for such systems. All closed-loop signals are bounded in probability and the error signals remain semiglobally bounded in the fourth moment (or mean square). Finally, the effectiveness and the applicability of the proposed control design are verified by two simulation examples.


Long noncoding antisense RNA FAM83A-AS1 promotes lung cancer cell progression by increasing FAM83A.
The abnormal expression of long noncoding RNAs (lncRNAs) is closely associated with human cancers. As one special group of lncRNAs, natural antisense transcripts (NATs) can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Their expression levels are altered in many cancers, but their roles are poorly understood. We strove to find NATs involved in human non-small-cell lung cancer (NSCLC) and to reveal their mechanism of action in cancer. We analysed the NATs in NSCLC from the TCGA database by circlncRNAnet. One NAT, family with sequence similarity 83 member A antisense RNA 1 (FAM83A-AS1), was found to be markedly upregulated and positively correlated with its cognate sense counterpart, FAM83A, in NSCLC. Moreover, overexpression of FAM83A-AS1 increased FAM38A protein levels and induced ERK1/2 phosphorylation downstream of FAM83A in cells. Finally, overexpression of FAM83A-AS1 promoted LUAD cell proliferation and invasion. In summary, lncRNA FAM83A-AS1 promotes LUAD by increasing FAM83A expression.


Autoantibodies in idiopathic inflammatory myopathy: an update on clinical and pathophysiological significance.
Idiopathic inflammatory myopathy is characterized by the production of autoantibodies to various cellular constituents. These autoantibodies closely correlate with certain clinical conditions and prognosis of disease. This review examines recent progress in myositis-specific autoantibodies, particularly in their clinical significance and pathophysiological roles. During the 1-year review period, novel myositis-specific autoantibodies were identified in clinically amyopathic dermatomyositis (anti-CADM-140 antibody) and malignancy-associated myositis (anti-p155 and anti-p155/p140 antibodies). These new autoantibodies are extremely important because it is thought that myositis-specific autoantibodies are negative in these subgroups, and may enable a new classification of idiopathic inflammatory myopathy. New clinical aspects of other myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetases, anti-signal recognition particles and anti-Mi-2) are also described. The possibility was raised that the high expression of myositis-specific autoantigens in regenerating muscle cells and certain cancers may be involved in initiating and perpetuating the autoimmune response in myositis. Myositis-specific autoantibodies are useful markers for clinical diagnosis, classification and predicting prognosis of idiopathic inflammatory myopathy. To understand the etiopathogenic mechanisms of the disease it is particularly important to elucidate the nature of target autoantigens recognized by these myositis-specific autoantibodies.


Student supervision: myth or reality?
This paper is based on the early findings of a qualitative longitudinal study using a grounded theory approach to analysis. A cohort of Project 2000 students and their clinical supervisors were observed in 10 different ward settings and interviewed prior to leaving the setting. A non-participant observation technique was utilized, noting the students' interactions with their deemed supervisors. The students and the supervisors were then interviewed using a semi-structured question format to explore supervision issues. The findings suggest that both students and supervisors in the study believe that supervision is an important learning strategy. However, what is believed in theory would not always appear to hold true in practice. The study identifies a limited knowledge by the supervisors of the skills and models of supervision, indicating the need for greater role preparation and a more clearly defined role specification. Supervision tended to focus upon tasks rather than issues. Furthermore, the role conflicts experienced by the supervisors was perceived as inhibiting facilitation of student learning. It is recommended that, for supervision to be more effective within the present operational constraints, it should utilize a more problem-solving approach, thus encouraging critical reflection on practice.


Outpatient Worsening Heart Failure as a Target for Therapy: A Review.
Hospitalizations for worsening heart failure (WHF) represent an enormous public health and financial burden, with physicians, health systems, and payers placing increasing emphasis on hospitalization prevention. In addition, maximizing time out of the hospital is an important patient-centered outcome. In this review, we discuss the concept of outpatient WHF, highlight the rationale and data for the outpatient treatment of WHF as an alternative to hospitalization, and examine opportunities and strategies for developing outpatient "interceptive" therapies for treatment of worsening symptoms and prevention of hospitalization. Worsening heart failure has traditionally been synonymous with an episode of in-hospital care for worsening symptoms. While WHF often leads to hospitalization, many patients experience WHF in the outpatient setting and carry a similarly poor prognosis. These findings support WHF as a distinct condition, independent of location of care. For those that are hospitalized, most patients have an uncomplicated clinical course, with diuretics as the only intravenous therapy. Although complicated scenarios exist, it is conceivable that improved tools for outpatient management of clinical congestion would allow a greater proportion of hospitalized patients to receive comparable care outside the hospital. Most patients with WHF have a gradual onset of congestive signs and symptoms, offering a potential window in which effective therapy may abort continued worsening and obviate the need for hospitalization. To date, outpatient WHF has received minimal attention in randomized clinical trials, but this high-risk group possesses key features that favor effective clinical trial investigation. As the public health and economic burdens of heart failure continue to grow, recognizing the entity of outpatient WHF is critical. Efforts to reduce heart failure hospitalization should include developing effective therapies and care strategies for outpatient WHF. The outpatient WHF population represents a major opportunity for therapeutic advancements that could fundamentally change heart failure care delivery.


Clinical presentation of patients with aseptic meningitis, factors influencing treatment and hospitalization, and consequences of enterovirus cerebrospinal fluid polymerase chain reaction testing.
Clinical and laboratory features of enteroviral meningitis may overlap with those of bacterial meningitis. In the present retrospective review, we compared features of enteroviral (EV)-positive and -negative patients to determine those that were most influential in admission, discharge and in anti-infective administration. Data were analyzed from the records of 117 pediatric and adult patients who underwent cerebrospinal fluid (CSF) EV testing over a three-year period. The oldest EV-positive patient was 34 years of age and the occurrence of the disease was highly seasonal. EV-positive patients were more likely to report fever, rash, photophobia, short onset and exposure to an ill contact. A positive polymerase chain reaction (PCR) result was associated with relatively short hospitalization. Seizure and neurological symptoms were more strongly associated with a negative PCR test result. CSF characteristics did not discriminate well between patients with positive and negative PCR tests. Patients with imperfect Glasgow Coma Scores or with neurological symptoms were more likely to be admitted to hospital than those without. Fever and recent onset predicted determinants of anti-infective use. The present retrospective study confirms previous reports regarding seasonality and the young age of positive patients. Factors that indicate nonenteroviral etiology were appropriately also those that influenced hospitalization. Patients with EV meningitis were likely to be treated with empirical anti-infectives, and a substantial proportion continued to take antibiotics for more than 24 h after receiving the positive EV PCR test result. Clinical and laboratory features of enteroviral meningitis may overlap with those of bacterial meningitis. In the present retrospective review, we compared features of enteroviral (EV)-positive and -negative patients to determine those that were most influential in admission, discharge and in anti-infective administration. Data were analyzed from the records of 117 pediatric and adult patients who underwent cerebrospinal fluid (CSF) EV testing over a three-year period. The oldest EV-positive patient was 34 years of age and the occurrence of the disease was highly seasonal. EV-positive patients were more likely to report fever, rash, photophobia, short onset and exposure to an ill contact. A positive polymerase chain reaction (PCR) result was associated with relatively short hospitalization. Seizure and neurological symptoms were more strongly associated with a negative PCR test result. CSF characteristics did not discriminate well between patients with positive and negative PCR tests. Patients with imperfect Glasgow Coma Scores or with neurological symptoms were more likely to be admitted to hospital than those without. Fever and recent onset predicted determinants of anti-infective use. The present retrospective study confirms previous reports regarding seasonality and the young age of positive patients. Factors that indicate nonenteroviral etiology were appropriately also those that influenced hospitalization. Patients with EV meningitis were likely to be treated with empirical anti-infectives, and a substantial proportion continued to take antibiotics for more than 24 h after receiving the positive EV PCR test result.


Control methods for mineral oil mists.
Effective mist collection is important, but it is not the only determinant of mist concentration in plant air. Oil-based metalworking fluids such as straight and soluble oils contain semivolatile hydrocarbons. When these fluids form a mist, their semivolatile components partition between the vapor and mist phases depending on the makeup of the mist and on local conditions. This article addresses the relationship between the concentrations of semivolatile hydrocarbons in the vapor and mist phases using theory for partitioning developed in the field of atmospheric chemistry. Mist can be removed effectively in a collector that uses a HEPA filter as its final collection stage. Acceptable HEPA lifetime requires effective upstream stages that reduce mist loading to the HEPA; furthermore, acceptable HEPA performance requires that it be installed and maintained properly. Collectors designed to remove mist do not remove vapor, and as collector exhaust mixes into cooler plant air that already contains some mist, vapor from the collector can repartition to increase the mist concentration in the plant. Assessing the effect of vapor-to-mist repartitioning is complicated; however, repartitioning may be important for many of the compounds contained in oil-based metalworking fluids. Conditions that minimize vapor-to-mist repartitioning, such as ventilating the plant with clean outdoor air, increasing plant temperature, or controlling the release of vapor, may also be expensive, uncomfortable to plant occupants, or impractical from an engineering standpoint. As a result, very low mist concentrations in plant air may be difficult to attain.


Enhanced circulating levels of CD3 cells-derived extracellular vesicles in different forms of pulmonary hypertension.
It has been shown previously that increased circulating endothelial cells-derived extracellular vesicles represent an important pathological attribute of pulmonary hypertension. Although it is a well-known fact that inflammatory cells may also release extracellular vesicles, and pulmonary hypertension is a disease associated with abnormal inflammation, there is no profound knowledge with regard to the role of inflammatory cells-derived extracellular vesicles. Therefore, our study demonstrated that circulating levels of extracellular vesicles derived from T-cells are enhanced in various pulmonary hypertension forms and that endothelial cells-derived extracellular vesicles may have distinctive profiles in different clinical subgroups of pulmonary hypertension, which still remains as a poorly treatable and life-threatening disorder.


Challenges in ethanol production with Fusarium oxysporum through consolidated bioprocessing.
Fusarium oxysporum has been reported as being able to both produce the enzymes necessary to degrade lignocellulosic biomass to sugars and also ferment the monosaccharides to ethanol under anaerobic or microaerobic conditions. However, in order to become an economically feasible alternative to other ethanol-producing microorganisms, a better understanding of its physiology, metabolic pathways, and bottlenecks is required, together with an improvement in its efficiency and robustness. In this report, we describe the challenges for the future and give additional justification for our recent publication.


Outer membrane protein mediating iron uptake via pyoverdinpss, the fluorescent siderophore produced by Pseudomonas syringae pv. syringae.
In an iron-limited environment Pseudomonas syringae pv. syringae B301D produces a yellow-green fluorescent siderophore called pyoverdinpss which functions in high-affinity iron transport. Two-dimensional electrophoretic comparisons of the outer membrane proteins of strain B301D identified nine proteins which were expressed at low (50 nM) but not at high (10 microM) iron concentrations. Except for the minor protein 8e, the iron-regulated proteins exhibited high molecular weights ranging from approximately 74,000 to 80,000. A mutant of strain B301D incapable of iron uptake (Iu-) from ferric pyoverdinpss lacked the 74,000-molecular-weight protein 4a, which was the major iron-regulated outer membrane protein. In contrast, a nonfluorescent mutant (Flu-) unable to synthesize pyoverdinpss showed no quantitative or qualitative difference in its outer membrane profile from that of the wild-type strain. In plant pathogenicity tests the Iu- and Flu- strains caused typical brown necrotic and sunken lesions in immature sweet cherry fruit which were indistinguishable from those of the wild-type strain. Thus, excretion of pyoverdinpss and subsequent Fe(III) uptake do not have a determinative role in the pathogenicity or virulence of P. syringae pv. syringae.


Aflatoxins in liver biopsies from Sudanese children.
Aflatoxin analysis of 40 percutaneous needle liver biopsies in 27 children with protein-energy malnutrition and 13 children with miscellaneous liver disease in The Sudan is reported. Aflatoxins B1, B2 and aflatoxicol were detected in 5 of the 16 biopsies from kwashiorkor but in none of 11 biopsies from marasmus or marasmic kwashiorkor. Aflatoxins G1, G2 and M2 were detected in 5 of 12 children with chronic liver disease. A very high concentration of aflatoxicol was found in a breast-fed infant with neonatal hepatitis of unknown etiology.


Comparing Unicompartmental Knee Arthroplasty and High Tibial Osteotomy for Isolated Medial Compartment Knee Osteoarthritis.
Both unicompartmental knee arthroplasty (UKA) and high tibial osteotomy (HTO) allow for compartment-specific intervention on an arthritic knee joint that preserves bone stock and native soft tissue compared to a total knee arthroplasty (TKA). Both operations give a more natural feeling with native proprioception compared with a TKA. HTO is better suited in patients who are younger (<55 years-of-age), have a body mass index (BMI) <30 kg/m2, high activity requirements, mechanical malalignment, asymmetric varus, isolated anterior cruciate ligament insufficiency, need for multiplanar correction, and a preference for joint preserving interventions. Recent data suggest that age (>55 years-of-age) should not solely contraindicate a HTO. UKA may be chosen in patients who are older (>55 years-of-age), low activity requirements, have a BMI <40 kg/m2, severe osteoarthritis with significant joint space narrowing, acceptable coronal alignment, symmetric varus, and patient preference for arthroplasty.


Unleashing the horizons of labor quality, digitalization on upgradation of industrial structure in Asian economies.
A country's industrial structure plays a pivotal role in determining its competitiveness, growth, and sustainability. Recently, many Asian countries have experienced significant economic upgradation and transformation and have emerged as major players in global trade. It is crucial to understand the factors contributing in upgradation of industrial structure of Asian economies for their continuous progress and it is little focused in literature. This study explores the effect of labor quality and digitalization on the upgradation of the industrial structure in 32 Asian countries covering the time period from 2010-2021. Multiple econometric techniques are applied for a comprehensive analysis of data, and the findings show that high-quality labor has a positive contribution to upgrading the industrial structure. Moreover, digitalization upgrades the industrial structure by improving connectivity, fostering collaboration, and enhancing productivity. Based on the findings of this study, Asian countries should prioritize investments in education and skill development to enhance human capital quality. Additionally, they should promote policies that facilitate digitalization, including investments in digital infrastructure, the development of digital skills, and the creation of a supportive regulatory environment. Thus, Asian countries can accelerate the upgradation of their industrial structure, leading to sustainable economic growth, increased competitiveness, and improved living standards.


Streptozotocin-induced non-insulin-dependent diabetes protects the heart from infarction.
The vulnerability of the myocardium of a diabetic animal to an ischemic insult is controversial. To address this issue, streptozotocin-induced non-insulin-dependent diabetes (NIDD) was induced in rats, and the effects of regional myocardial ischemia were assessed by measuring infarct size. Open-chest rats with NIDD and age-matched control rats underwent 30 or 45 minutes of regional ischemia and 2-hour reperfusion. Infarct size was measured by tetrazolium. Control rats had 32.0 +/- 3.3% infarction of the risk zone after a 30-minute coronary occlusion, whereas NIDD rats had significantly smaller infarcts (11.5 +/- 3.1% of the risk area, P < .005). When ischemic time was extended to 45 minutes, infarct size in control animals averaged 57.9 +/- 6.2%, whereas only 37.3 +/- 5.6% of ischemic myocardium was infarcted in NIDD rats (P < .05). In a subset NIDD group, rats experienced a period of ischemic preconditioning (three cycles of 5-minute ischemia/5-minute reperfusion) before 45-minute ischemia. Infarct size in these rats averaged only 6.9 +/- 3.0% (P < .01 vs nonpreconditioned NIDD rats with 45-minute coronary occlusions). Collateral flow was measured in NIDD rat hearts with radioactive microspheres. Collateral flow was < 1% of normal myocardial blood flow. We conclude that NIDD protects the heart from infarction and that this protection is not related to the development of coronary collaterals. Furthermore, preconditioning can further protect the NIDD heart.


Posterior polymorphous dystrophy--a histopathologic presentation.
The corneal button from a 34-year-old woman with posterior polymorphous dystrophy was studied by light and electron microscopy. Ultrastructural findings showed coexistence of epithelial-like cells and abnormal endothelial cells, and Descemet's membrane composed of a normal anterior banded layer, and an irregular posterior homogeneous and collagenous layer. We suggest that these abnormal endothelial cells are in the process of transforming into epithelial-like cells.


[Acute lumbar disk displacement with nerve root compression. Indications for peridural steroid injection].
The rationale and indication, but also the efficacy and limitation of lumbar epidural corticosteroid injection in patients suffering from acute lumbosacral radicular pain are explained. Epidural administration of corticosteroids with longterm effect and bupivacaine by a translumbar approach in patients suffering from acute low back pain and sciatica causes an immediate, persistent pain relief and a more prompt regression of nerve root compression compared to patients just treated by bed rest and analgesics. The state of the art is based on recent meta-analyses and the understanding of the pathophysiology of discal hernia which includes inflammation. Contemporary concepts and data from recent reviews are summarized to elucidate current recommendations and suggestions for the management of patients with acute sciatica. The postulate of an application performed by an experienced anaesthesiologist is stressed. Advantages of this invasive form of therapy include reduction of addictive analgesic drugs, decreased time of absolute immobilisation, respectively strict bed rest, and of hospitalisation.


Nearest-neighbor nonparametric method for estimating the configurational entropy of complex molecules.
A method for estimating the configurational (i.e., non-kinetic) part of the entropy of internal motion in complex molecules is introduced that does not assume any particular parametric form for the underlying probability density function. It is based on the nearest-neighbor (NN) distances of the points of a sample of internal molecular coordinates obtained by a computer simulation of a given molecule. As the method does not make any assumptions about the underlying potential energy function, it accounts fully for any anharmonicity of internal molecular motion. It provides an asymptotically unbiased and consistent estimate of the configurational part of the entropy of the internal degrees of freedom of the molecule. The NN method is illustrated by estimating the configurational entropy of internal rotation of capsaicin and two stereoisomers of tartaric acid, and by providing a much closer upper bound on the configurational entropy of internal rotation of a pentapeptide molecule than that obtained by the standard quasi-harmonic method. As a measure of dependence between any two internal molecular coordinates, a general coefficient of association based on the information-theoretic quantity of mutual information is proposed. Using NN estimates of this measure, statistical clustering procedures can be employed to group the coordinates into clusters of manageable dimensions and characterized by minimal dependence between coordinates belonging to different clusters.


[Communicative function of dreams in the therapeutic process].
Sleep is not a loss of consciousness, but an altered state of consciousness. What appears in the dream is preconscious and ready to move into consciousness. This material may be manifested also during free association. The difference between free association and REM dreaming is that the preconscious material is presented in response to internal and/or external stimuli in a more coherent form during free associations, whereas during a REM dream, the material of daily experiences and perceptions that are fragmented in the preconscious are recombined in a less coherent form. The material that cannot be easily expressed during free association in the wakeful state, due to inner or external inhibition, appear in dreams and thus, find an easier way of expression. The dreams of patients who have difficulty directly expressing their thoughts, feelings, and experiences serve as a useful means of communication during the initial stage of therapy and provide valuable analytic material to help the progress of the psychoanalytic treatment. This phenomenon is described with a case presentation. The very inhibited patient who could not openly express her life experiences, emotions, and conflicts found it easier to report her dreams at the beginning of the therapeutic process. Through the material presented from these dreams, it became possible to open the path to direct verbal communication, to work through her problems, and to monitor the progress of the therapeutic process.


Core-shell nanoparticles based on pullulan and poly(β-amino) ester for hepatoma-targeted codelivery of gene and chemotherapy agent.
This study designs a novel nanoparticle system with core-shell structure based on pullulan and poly(β-amino) ester (PBAE) for the hepatoma-targeted codelivery of gene and chemotherapy agent. Plasmid DNA expressing green fluorescent protein (pEGFP), as a model gene, was fully condensed with cationic PBAE to form the inner core of PBAE/pEGFP polycomplex. Methotrexate (MTX), as a model chemotherapy agent, was conjugated to pullulan by ester bond to synthesize polymeric prodrug of MTX-PL. MTX-PL was then adsorbed on the surface of PBAE/pEGFP polycomplex to form MTX-PL/PBAE/pEGFP nanoparticles with a classic core-shell structure. MTX-PL was also used as a hepatoma targeting moiety, because of its specific binding affinity for asialoglycoprotein receptor (ASGPR) overexpressed by human hepatoma HepG2 cells. MTX-PL/PBAE/pEGFP nanoparticles realized the efficient transfection of pEGFP in HepG2 cells and exhibited significant inhibitory effect on the cell proliferation. In HepG2 tumor-bearing nude mice, MTX-PL/PBAE/pEGFP nanoparticles were mainly distributed in the tumor after 24 h postintravenous injection. Altogether, this novel codelivery system with a strong hepatoma-targeting property achieved simultaneous delivery of gene and chemotherapy agent into tumor at both cellular and animal levels.


Dialysis dementia.
Dialysis dementia is a unique neurologic complication of renal failure associated with chronic dialysis. While many questions remain about the pathophysiology of the disease, aluminum toxicity is probably the major factor in the pathogenesis of the dementia. Reducing dialysate aluminum levels and minimizing oral aluminum intake has markedly decreased the incidence of the disease. Deferoxamine, a chelating agent, is effective if it is given early; however, chronic use may lead to serious complications, although they are rare.


The Ex Situ Comparison of Two Improved St. John's wort (Hypericum perforatum) Cultivars with an Iranian Wild Population.
This research is part of an ongoing selection and breeding effort to target Iranian genotypes of Hypericum perforatum with the potential to produce higher amounts of desired secondary metabolites and greater resistance to fungal pathogens. There is a significant interest in the development of such cultivars to supply materials to the local pharmaceutical industries. For this reason, two improved cultivars of H. perforatum ("Gold" and "Veperikon") were compared with a wild Iranian population (Ardabile population) under common garden conditions in Iran. Plants were cultivated from seed in a greenhouse and seedlings were transplanted after one month to the field plots. The statistical design of this study was a Randomized Complete Block Design with three replications. During the period of full flowering, selected phenological (number of days to flowering), morphological (plant height, mean leaf area, number of black glands/leaf) and chemical (hypericin and pseudohypericin content) characteristics were assessed. Our observations were that the "Veperikon" cultivar is very sensitive to soil-borne diseases. All transplanted seedlings were infected by the plant pathogenic fungus Colletotrichum gloeosporioides, which caused necrosis of the whole plant. Both the "Gold" cultivar and plants from the wild population persisted despite mild infections with C. gloeosporioides and produced flowering shoots at both the first and second years after cultivation. The "Gold" cultivar was superior to the Ardabile population in terms of phenological and morphological characteristics. The average naphthodianthrone content (% dry weight of tissue) for the wild Iranian population was 0.04(±0.01)%, but for the "Gold" cultivar, 0.33(±0.43)%. These data indicate that selection and directed cultivation of Iranian H. perforatum plants can result in plants with improved morphological, phenological and chemical characteristics.