The adenine nucleotide-binding site on yeast 3-phosphoglycerate kinase. Affinity labeling of Lys-131 by pyridoxal 5'-diphospho-5'-adenosine.
The adenine nucleotide analog [3H]pyridoxal 5'-diphospho-5'-adenosine (PLP-AMP) is a potent and highly specific inactivator of yeast 3-phosphoglycerate kinase. Supportive evidence includes the finding that 1) during a 10-min incubation, half-maximal inactivation is given by 10 microM PLP-AMP, 2) covalent incorporation of 1.2 mol of PLP-AMP/mol of enzyme is sufficient to give complete inactivation, and 3) MgATP gives near complete protection against modification and inactivation by PLP-AMP. Following reaction with PLP-AMP and reduction with NaBH4 to form a stable adduct, the enzyme was digested with endoproteinase Lys-C and peptides were separated by reversed-phase high-performance liquid chromatography. The single major labeled peptide was purified and sequenced, and the modified residue was identified as Lys-131. The crystal structure of enzyme in the open conformation shows Lys-131 to reside within a loop of flexible random coil positioned at the outer edge of the central binding cleft, approximately 2 nm from the surface of the cleft that comprises part of the MgATP-binding site (Watson, H. C., Walker, N. P. C., Shaw, P. J., Bryant, T. N., Wendell, P. L., Fothergill, L. A., Perkins, R. E., Conroy, S. C., Dobson, M. J., Tuite, M. F., Kingsman, A. J., and Kingsman, S. M. (1982) EMBO J. 1, 1635-1640). We conclude that the structural element containing Lys-131 undergoes substantial movement during the ligand-induced conformational change known to occur during formation of the ternary complex, resulting in the positioning of a basic residue near a negatively charged substrate. Since similar affinity-labeling results have been presented for hexokinase (Tamura, J. K., LaDine, J. R., and Cross, R. L. (1988) J. Biol. Chem. 263, 7907-7912), we further suggest that movement of positive charge into the central cleft may be a common step in the tight binding of nucleotides by bilobal kinases.


Seasonal variation in peritoneal dialysis-associated peritonitis: a multi-centre registry study.
The role of seasonal variation in peritoneal dialysis (PD)-related peritonitis has been limited to a few small single-centre studies. Using all 6610 Australian patients receiving PD between 1 October 2003 and 31 December 2008, we evaluated the influence of seasons on peritonitis rates (Poisson regression) and outcomes (multivariable logistic regression). The overall rate of peritonitis was 0.59 episodes per patient-year of treatment. Using winter as the reference season, the peritonitis incidence rate ratios (95% confidence interval) for summer, autumn and spring were 1.02 (0.95-1.09), 1.01 (0.94-1.08) and 0.99 (0.92-1.06), respectively. Significant seasonal variations were observed in the rates of peritonitis caused by coagulase-negative Staphylococci (spring and summer peaks), corynebacteria (winter peak) and Gram-negative organisms (summer and autumn peaks). There were trends to seasonal variations in fungal peritonitis (summer and autumn peaks) and pseudomonas peritonitis (summer peak). No significant seasonal variations were observed for other organisms. Peritonitis outcomes did not significantly vary according to season. Seasonal variation has no appreciable influence on overall PD peritonitis rates or clinical outcomes. Nevertheless, significant seasonal variations were observed in the rates of peritonitis due to specific microorganisms, which may allow institutions to more precisely target infection control strategies prior to higher risk seasons.


[Status of organ transplantation of the kidney, liver and small intestine: aspects of biological and artificial organ replacement].
Substitution of all functions of an organ failure is characteristic for organ transplantation, whilst artificial organ supply is confined to some essential functions. But technical organ substitution would be unlimited in performance, in contrast to organ transplantation, which depends on availability of human organs. Thus, according to the example in substitution of renal failure, those, organ transplantation and technical organ supply have to be worked out furthermore in other organ systems, thus in liver and small intestine substitution. In future, technical supply will change to biotechnical methods and organ grafting will develop to a long lasting therapeutic procedure.


Effects of alcohol-induced human peripheral blood mononuclear cell (PBMC) pretreated whey protein concentrate (WPC) on oxidative damage.
Excessive alcohol consumption can induce apoptosis in a variety of tissues and influence the antioxidant status in peripheral blood mononuclear cells (PBMC). This paper investigates the effects of whey protein concentrate (WPC) pretreated in PBMC on the apoptosis and antioxidant status after the treatment of alcohol. The results show that the percentages of apoptotic cells in the alcohol-treated group were higher than those in the group without alcohol treatment. Additionally, there was higher glutathione (GSH) peroxidase (GPx) activity when the PBMC were treated with 300 mg/dL of alcohol. With regard to the activity of GSH reductase (GRx), there was higher activity in the group pretreated with WPC than in the group with the treatment of alcohol only. On the contrary, the levels of GSH were reduced after the treatment of alcohol, but there was a higher level of GSH in the group pretreated with WPC. In this study, it was found that the increased level of GSH in PBMC might not be attributed to the effect of GRx because there was still a higher level of GSH in the group with the treatment of WPC and BCNU (a GRx inhibitor) in this study. The results indicated that PBMC pretreated with WPC might ameliorate alcohol-induced effects such as imbalance of the antioxidant status.


Lessons from export to New Zealand of the second opinion appointed doctor scheme.
Aims and method We compared findings of an audit of New Zealand's version of the second opinion appointed doctor (SOAD) scheme with published information on the equivalent scheme for England and Wales, to consider what might be learnt from the different jurisdictions' experience. Results Strong similarities exist between the two schemes in the demographic profile of individuals subject to the SOAD process and rates of approval of compulsory treatment. The clearer legal framework for the English scheme and its supervision by an independent national agency may offer significant advantages in terms of consistency and transparency, compared with the informal, decentralised structure of New Zealand's scheme. Clinical implications Clinicians may not always favour greater formality or elaborate national structures for administering the Mental Health Act, but there are advantages in promoting clarity and consistency in a mandatory statutory process designed to protect compulsory patients' rights.


HYALURONIC ACID IN ORTHOPEDICS.
Hyaluronic acid (HA) as a compound was discovered in 1934 by Karl Meyer and John Palmer as one of the glycosaminoglycans (GAG) in the vitreous body of the bovine eye. HA occurs naturally in many organs, tissues and body fluids, and especially is presented in large quantities in articular cartilage and synovial fluid. It is a non-protein, non-sulfate glycosaminoglycan which has an important role in the physiological biomechanics of synovial fluid, there is responsible for lubrication and drug-elasticity. In the musculoskeletal system, hyaluronic acid is produced by synoviocytes, fibroblasts and chondrocytes. The concentration of hyaluronic acid decreases not only with age, but also in connection with the progression of certain diseases, for example osteoarthritis (OA). For this reason, it has been used for almost 50 years to try to alleviate and treat symptoms of OA in humans and animals. Numerous studies confirmed the beneficial effect of hyaluronic acid supplementation in OA. Patients which has intraarticular viscosupplementation of HA experience less pain and have a reduced need to take nonsteroidal anti-inflammatory drugs. Intra articular HA administration shows a low risk of local and systemic side effects while maintaining proper administration under aseptic conditions. Nevertheless, local inflammatory reactions occur, but it are most often self-limiting or do not require invasive treatment. The issue of recommending hyaluronic acid in osteoarthritis is still ambiguous and controversial.


Explore the influence of BMI in the optimal time of weaning from sequential mechanical ventilation for severity chronic obstructive pulmonary disease.
To study the clinical effect of body mass index (BMI) in the optimal time of weaning from sequential invasive-noninvasive mechanical ventilation (MV) by treating severity chronic obstructive pulmonary disease (COPD) patients. 94 patients with severity COPD were divided into the control group (BMI<21) and the study group (BMI>21). These two groups were treated by similar symptomatic therapies such as mechanical ventilation, antibacterial, antispasmodic, relieving asthma, antitussive, expectorant, correction of electrolyte imbalance and acid-base balance disorders, strengthen nutritional support, etc. Compared with the control group, the study group had shorter duration of invasive mechanical ventilation, non-invasive mechanical ventilation time, total mechanical ventilation time, total hospital stay (P<0.01). There are significant differences between these two groups in re-intubation rate, VAP occurred in the number of case, hospital mortality rate in 28 days (P<0.05). It is difficult to wean successfully from sequential mechanical ventilation for severity COPD patients (BMI<21), so BMI as one of important reference index can be used to estimate the optimal time for weaning from sequential mechanical ventilation for severity COPD patients.


An examination of reforms on the social security system of retirement based on practices in Hainan province.
"The first task of this article is to analyze and dissect the seven major drawbacks of the current disjointed retirement system [in China] characterized by collection of pension for immediate distribution. This will be followed by an introduction of the reforms on the social security system of elderly support for enterprise retirees carried out in Hainan Province and specific social security and elderly support practices by private businesses in Haikou, capital city of Hainan Province....Special inquiries are made regarding the necessity and feasibility of establishing a national uniform social security system of elderly support covering civil servants, enterprise workers, private business owners, managers, and employees and farmers."


Long-Term Outcomes and Echocardiographic Data After Aortic Valve Replacement With a 17-mm Mechanical Valve.
We investigated the long-term clinical and hemodynamic outcomes after aortic valve replacement (AVR) with a 17-mm mechanical valve.Methods and Results:Between January 2005 and December 2011, 80 patients with aortic stenosis underwent AVR with the 17-mm St. Jude Medical Regent prosthetic valve. Echocardiography was performed preoperatively, at discharge, and at follow-up, which was performed at least 2 years postoperatively (median interval, 7.3 years). Prosthesis-patient mismatch (PPM) was defined as an indexed effective orifice area <0.85 cm2/m2at discharge and occurred in 25 patients (31%). The median follow-up period was 8.7 years (100% complete). Overall in-hospital mortality was 2.5% (2 patients) with 27 late deaths (34%). The 5- and 10-year survival rates were 78.7% and 63.0%, respectively. Peripheral arterial disease and concomitant mitral valve repair were independent predictors of late mortality. The 5- and 10-year freedom from major adverse valve-related events (MAVRE) rates were 91.6% and 83.5%, respectively. PPM at discharge did not affect long-term survival, freedom from MAVRE, or freedom from heart failure. Echocardiographic data at follow-up revealed a significant reduction in the mean left ventricular mass index (LVMI). LVMI reduction observed at follow-up was similar between patients with and without PPM. AVR with the 17-mm mechanical prosthesis had acceptable long-term clinical and hemodynamic outcomes. Significant reduction in LVMI was observed regardless of PPM.


Effect of the structure of lipids favoring disordered domain formation on the stability of cholesterol-containing ordered domains (lipid rafts): identification of multiple raft-stabilization mechanisms.
Despite the importance of lipid rafts, commonly defined as liquid-ordered domains rich in cholesterol and in lipids with high gel-to-fluid melting temperatures (T(m)), the rules for raft formation in membranes are not completely understood. Here, a fluorescence-quenching strategy was used to define how lipids with low T(m), which tend to form disordered fluid domains at physiological temperatures, can stabilize ordered domain formation by cholesterol and high-T(m) lipids (either sphingomyelin or dipalmitoylphosphatidylcholine). In bilayers containing mixtures of low-T(m) phosphatidylcholines, cholesterol, and high-T(m) lipid, the thermal stability of ordered domains decreased with the acyl-chain structure of low-T(m) lipids in the following order: diarachadonyl > diphytanoyl > 1-palmitoyl 2-docosahexenoyl = 1,2 dioleoyl = dimyristoleoyl = 1-palmitoyl, 2-oleoyl (PO). This shows that low-T(m) lipids with two acyl chains having very poor tight-packing propensities can stabilize ordered domain formation by high-T(m) lipids and cholesterol. The effect of headgroup structure was also studied. We found that even in the absence of high-T(m) lipids, mixtures of cholesterol with PO phosphatidylethanolamine (POPE) and PO phosphatidylserine (POPS) or with brain PE and brain PS showed a (borderline) tendency to form ordered domains. Because these lipids are abundant in the inner (cytofacial) leaflet of mammalian membranes, this raises the possibility that PE and PS could participate in inner-leaflet raft formation or stabilization. In bilayers containing ternary mixtures of PO lipids, cholesterol, and high-T(m) lipids, the thermal stability of ordered domains decreased with the polar headgroup structure of PO lipids in the order PE > PS > phosphatidylcholine (PC). Analogous experiments using diphytanoyl acyl chain lipids in place of PO acyl chain lipids showed that the stabilization of ordered lipid domains by acyl chain and headgroup structure was not additive. This implies that it is likely that there are two largely mutually exclusive mechanisms by which low-T(m) lipids can stabilize ordered domain formation by high-T(m) lipids and cholesterol: 1), by having structures resulting in immiscibility of low-T(m) and high-T(m) lipids, and 2), by having structures allowing them to pack tightly within ordered domains to a significant degree.


Transmission of mechanical stresses within the cytoskeleton of adherent cells: a theoretical analysis based on a multi-component cell model.
How environmental mechanical forces affect cellular functions is a central problem in cell biology. Theoretical models of cellular biomechanics provide relevant tools for understanding how the contributions of deformable intracellular components and specific adhesion conditions at the cell interface are integrated for determining the overall balance of mechanical forces within the cell. We investigate here the spatial distributions of intracellular stresses when adherent cells are probed by magnetic twisting cytometry. The influence of the cell nucleus stiffness on the simulated nonlinear torque-bead rotation response is analyzed by considering a finite element multi-component cell model in which the cell and its nucleus are considered as different hyperelastic materials. We additionally take into account the mechanical properties of the basal cell cortex, which can be affected by the interaction of the basal cell membrane with the extracellular substrate. In agreement with data obtained on epithelial cells, the simulated behaviour of the cell model relates the hyperelastic response observed at the entire cell scale to the distribution of stresses and strains within the nucleus and the cytoskeleton, up to cell adhesion areas. These results, which indicate how mechanical forces are transmitted at distant points through the cytoskeleton, are compared to recent data imaging the highly localized distribution of intracellular stresses.


Exercise-induced asthma. Diagnostic clues with recommendation for treatment.
Exercise-induced bronchospasm, a very common component of asthma, may be quite bothersome and interfere with activities. The etiology appears to be related to the degree of heat loss in the tracheobronchial tree and to release of mediators from the mast cells. Exercise-induced asthma can be effectively treated, preferably with preventive medications such as beta 2 agonists or cromolyn (Intal). In the future, drugs such as nifedipine (Procardia) may also be useful, but as yet no calcium channel blocker has been approved for this indication.


Preparation of Eu-Doped Y(2)O(3) Luminescent Nanoparticles in Nonionic Reverse Microemulsions.
In this study, Y(2)O(3):Eu luminescent nanoparticles were prepared by precipitation of aqueous yttrium nitrate/europium nitrate solution using ammonium hydroxide in the reverse microemulsions based on polyoxyethylene (5) nonylphenyl ether/polyoxyethylene (9) nonylphenyl ether, cyclohexane, and water. With Eu-doped Y(2)O(3) nanoparticles obtained, particle size, shape, chemical composition, crystalline formation rate, crystallinity, and photoluminescence were measured and compared with those of particles formed by a bulk precipitation method. The nanoparticles synthesized in microemulsion showed a narrow size distribution, spherical shape, fast crystalline formation rate, high crystallinity, and strong photoluminescence. This stronger photoluminescence of particles formed in a microemulsion might be attributed to more densely packed particles with very few voids and higher crystallinity at a relatively low temperature than those synthesized through a bulk precipitation method. Copyright 2000 Academic Press.


Retinal abnormalities in human albinism translate into a reduction of grey matter in the occipital cortex.
Albinism is a genetic condition associated with abnormalities of the visual system. Defects in melanin production cause underdevelopment of the fovea, reduced retinal cell numbers and abnormal routing of ganglion cell nerve fibres at the optic chiasm. We examined 19 subjects with albinism and 26 control subjects to determine whether retinal abnormalities affect the structure of the visual cortex. Whole-brain, high-resolution anatomical magnetic resonance imaging volumes from each subject were obtained on a 1.5-T scanner and segmented into grey and white matter. A voxel-wise statistical comparison of grey and white matter volumes in the occipital lobes between the two groups was performed using voxel-based morphometry. Our analysis revealed a regionally specific decrease in grey matter volume at the occipital poles in albinism. The location of the decrease in grey matter corresponds to the cortical representation of the central visual field. This reduction is likely to be a direct result of decreased ganglion cell numbers in central retina in albinism.


The offspring-size/clutch-size trade-off in mammals.
The Smith-Fretwell model for optimal offspring size assumes the existence of an inverse proportional relationship (i.e., trade-off) between the number of offspring and the amount of resources invested in an individual offspring; virtually all of the many models derived from theirs make the same trade-off assumption. Over the last 30 years it has become apparent that the predicted proportionality is often not observed when evaluated across species. We develop a general allometric approach to correct for size-related differences in the resources available for reproduction. Using data on mammals, we demonstrate that the predicted inverse proportional relationship between number of offspring and offspring size is closely approached after correcting for allocation, though there is a slight curvature in the relationship. We discuss applications for this approach to other organisms, possible causes for the curvature, and the usefulness of allometries for estimating life-history variables that are difficult to measure.


Morphology evolution of fcc Ru nanoparticles under hydrogen atmosphere.
Tuning the morphology and structural evolution of metal nanoparticles to expose specific crystal facets in a certain reaction atmosphere is conducive to designing catalysts with a high catalytic activity. Herein, coverage dependent hydrogen adsorption on seven fcc Ru surfaces was investigated using density functional theory (DFT) calculations. The morphology evolution of the fcc Ru nanoparticles under the reactive environment was further illustrated using the multiscale structure reconstruction (MSR) model, which combines the DFT results with the Fowler-Guggenheim (F-G) adsorption isotherm and the Wulff construction. At constant pressure, the shape of a fcc Ru nanoparticle changes from a rhombic dodecahedron to a truncated octahedron with an increase of the temperature. More importantly, the desired Ru morphology, with abundant open facets, was predicted to occur at a high temperature and low pressure. Our results provide an insightful understanding of the reshaping of Ru nanoparticles during real reactions, which is crucial for its rational design for use as a nanocatalyst.


Is primary aldosteronism associated with diabetes mellitus? Results of the German Conn's Registry.
Aldosterone excess in the context of primary aldosteronism (PA) has been associated with impaired glucose tolerance and diabetes mellitus. We retrospectively assessed the prevalence of diabetes mellitus in patients from the German Conn's Register and compared the data with those from hypertensive subjects of a population-based survey. In a case-control study, we have compared 638 patients with PA from the German Conn's registry who were treated in 6 German centers with 897 hypertensive control subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg (KORA). The samples were matched for age, sex, and blood pressure in a 1:1 ratio. Risk factors associated with the presence of diabetes mellitus were calculated in 638 patients with PA and 897 hypertensive controls. In the case control study, the diabetes prevalence was calculated in 338 cases and controls. In patients with primary aldosteronism, age, BMI, and a higher number of antihypertensive drugs (lowest tertile vs. highest tertile) were variables associated with diabetes mellitus. In contrast, serum potassium and plasma aldosterone concentrations were not associated with higher diabetes prevalence, whereas diastolic blood pressure was inversely associated with diabetes mellitus. Diabetes mellitus was more prevalent in patients with PA than in 338 matched controls (23 vs. 10% in controls). Our data for the German population show that diabetes mellitus is more prevalent in patients with primary aldosteronism than in hypertensive controls.


The Protective Effects of Water Extracts of Compound Turmeric Recipe on Acute Alcoholism: An Experimental Research Using a Mouse Model.
Acute alcoholism (AAI) is a common emergency. Currently, there is a lack of preventive and therapeutic drugs with superior safety and efficacy. Curcuma longa, Panax ginseng, Pueraria lobata, Pueraria flower, and Hovenia dulcis Thunb., which are the components of compound turmeric recipe (CTR), are, respectively, used in China as adjuvant therapeutic agents for AAI and alcoholic liver injury, respectively. The purpose of this research was to investigate the effect of traditional compound turmeric recipe in anti-inebriation treatment and to identify its underlying mechanisms. The mice were administered with CTR mixture, and ethanol was subsequently given to mice by gavage. The effects of CTR on the righting reflex, 24-hour survival, drunken behavior, blood ethanol concentration, and pathological changes of liver are depicted. The activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were detected. Besides, the activities of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), cytochrome P450 (P450), superoxide dismutase (SOD), and malondialdehyde (MDA) in the liver and the levels of β-endorphin (β-EP) and leucine enkephalin (LENK) in the brain were also measured. Our results demonstrated that CTR can increase the activities of ADH, ALDH, P450, and SOD and decrease the contents of TNF-α, IL-8, and MDA in the liver. In addition, it can decrease the activities of ALT, AST, and ALP in serum and β-EP and LENK activities in the brain. CTR showed effects on prevention of acute alcoholism, promoting wakefulness, and alleviating alcoholic liver injury, which were likely mediated by the above mechanisms.


Serum cartilage oligomeric matrix protein and other biomarker profiles in tibiofemoral and patellofemoral osteoarthritis of the knee.
There is some evidence that tibiofemoral osteoarthritis (TFJ OA) and patellofemoral osteoarthritis (PFJ OA) may have different risk factors. To investigate the possibility that these conditions are separate disease entities, we compared biomarker profiles of patients with each disease. Serum samples were taken from 222 patients who had knee pain and X-ray signs of knee OA. Eighty-two had only medial TFJ OA and 38 only PFJ OA in one or both knees. The remaining patients had either mixed disease or equivocal radiographic evidence of OA. The following biomarkers were measured in serum samples from baseline and follow-up visits: cartilage oligomeric matrix protein (COMP), glycosaminoglycan, keratan sulphate epitope 5D4, YKL-40, osteocalcin, C-telopeptide of type I collagen, hyaluronan and C-reactive protein. The two subsets of OA (TFJ and PFJ) had similar radiographic disease severity and there were no significant differences in the presence and patterns of pain scores (visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index). No difference was found for the biomarkers between the two groups, with one exception. Both baseline and area under the curve per month COMP concentrations were significantly higher in the TFJ than the PFJ group (P<0.01). The reduced serum COMP in PFJ disease compared with TFJ OA could be due to small articular cartilage volume in the latter or to a qualitative difference in cartilage metabolism.


Surveillance for outbreaks of influenza-like illness in the institutionalized elderly.
Respiratory outbreaks are common in aged-care facilities (ACFs), are both underreported and frequently identified late, and are often associated with considerable burden of illness and death. There is emerging evidence that active surveillance coupled with early and systematic intervention can reduce this burden. Active surveillance for influenza-like illness and rapid diagnosis of influenza were established in 16 ACFs in Sydney, Australia, prior to the winter of 2006. A point-of-care influenza test and laboratory direct immunofluorescence tests for common respiratory viruses were used for diagnosis. We achieved early identification of seven respiratory disease outbreaks, two of which were caused by influenza. For the influenza outbreaks, antiviral treatment and prophylaxis were initiated 4-6 days from symptom onset in the primary case. A simple active surveillance system for influenza was successfully implemented and resulted in early detection of influenza and other respiratory disease outbreaks. This enabled earlier implementation of prevention and control measures and increased the potential effectiveness of anti-influenza chemoprophylaxis.


Development of percutaneously insertable/removable interspinous process spacer for treatment of posture-dependent lumbar spinal-canal stenosis: preclinical feasibility study using porcine model.
A procedure using an interspinous process spacer (IPS) was recently developed for the treatment of posture-dependent lumbar spinal-canal stenosis (LSS) patients. We developed a novel IPS which can be inserted with simpler procedures and removed percutaneously. The objectives of this study were: (1) to evaluate the feasibility and safety of this novel technique, and (2) to assess the effectiveness of this spacer in terms of preventing an increase of epidural pressure in lumbar extension using a porcine model. Eight young pigs were used. Under general anesthesia and image guidance, the spacers were inserted. Three months after operation, MR images were taken and all spacers were removed. Blood samples were obtained before and 1, 3, 7 days after surgery. After killing the animals, the lumbar spines were observed macroscopically. Another six animals were used. Under general anesthesia and image guidance, a flexible pressure transducer was inserted into the epidural space and epidural pressure was measured in neutral and at maximum extension with and without spacer insertion. Percutaneous insertion and removal of the spacer was successful for all animals through small skin incisions. MR images showed minimal damage to the muscle. No significant up-regulation of Interleukin-6 (IL-6) and CRP was detected. Macroscopic observation of the lumbar spine 3 months after the operation revealed that the area of the interspinous process contacting with the inserted spacer showed some bone erosion/remodeling. Insertion of the spacer did not affect the epidural pressure in neutral but significantly prevented an increase of epidural pressure in lumber extension. This study demonstrated that the percutaneous insertion and removal of a novel IPS was feasible and safe using a simple technique. Furthermore, this procedure can be recognized as minimally invasive surgery from the viewpoint of skin incision, short insertion track, inflammatory mediators, and muscle damage. Improvements should be attempted in future studies using softer or more elastic materials for the spacer to lessen bone erosion/remodeling at contacting area of the inserted spacer.


Synthesis and characterization of rice husk biochar via hydrothermal carbonization for wastewater treatment and biofuel production.
The recent implication of circular economy in Australia spurred the demand for waste material utilization for value-added product generations on a commercial scale. Therefore, this experimental study emphasized on agricultural waste biomass, rice husk (RH) as potential feedstock to produce valuable products. Rice husk biochar (RB) was obtained at temperature: 180 °C, pressure: 70 bar, reaction time: 20 min with water via hydrothermal carbonization (HTC), and the obtained biochar yield was 57.9%. Enhancement of zeta potential value from - 30.1 to - 10.6 mV in RB presented the higher suspension stability, and improvement of surface area and porosity in RB demonstrated the wastewater adsorption capacity. Along with that, an increase of crystallinity in RB, 60.5%, also indicates the enhancement of the catalytic performance of the material significantly more favorable to improve the adsorption efficiency of transitional compounds. In contrast, an increase of the atomic O/C ratio in RB, 0.51 delineated high breakdown of the cellulosic component, which is favorable for biofuel purpose. 13.98% SiO2 reduction in RB confirmed ash content minimization and better quality of fuel properties. Therefore, the rice husk biochar through HTC can be considered a suitable material for further application to treat wastewater and generate bioenergy.


Genetic characterization of Listeria monocytogenes food isolates and pathogenic potential within serovars 1/2a and 1/2b.
A total of 39 Listeria monocytogenes strains isolated from raw milk, smoked meat, chicken carcass and reference strains, belonging to serovars 1/2a, 4a, 1/2b, 3b and 4b, were analysed by RAPD and by polymorphisms of the virulent genes inlAB and iap. Ten isolates, belonging to serovars 1/2a and 1/2b and, collected from raw milk and smoked meat, were further tested for pathogenicity by IP injection into mice. The clustering of the 39 L. monocytogenes strains in 3 groups at 0.45 similarity level, based on molecular typing, was observed. Distribution of serovars in these clusters was in agreement with the proposed three Listeria monocytogenes lineages. Within serovar 1/2b, the 50% lethal dose (LD50) ranged from 8.4 x 10(4) to 1.7 x 10(6) cfu.ml(-1). One of the serovar 1/2b strains, isolated from smoked meat, exhibited the lowest virulence potential evaluated by LD50 and by mean time to death (MTD) and, from this point of view, was completely different from the other strains. Our results suggest the existence of heterogeneity in virulence levels within serovars 1/2a and 1/2b. However, when comparing the isolates based on genotyping, virulence indicators and food origin, no relation could be assessed.


Effects of monovalent cations on the sodium-alanine interaction in rabbit ileum. Implication of anionic groups in sodium binding.
H, K, Rb, and Li inhibit Na-dependent alanine influx across the brush border of rabbit ileum. Kinetic analysis indicates that H and K behave as competitive inhibitors of influx so that increasing the concentration of H or K in the mucosal solution is kinetically indistinguishable from decreasing the Na concentration. In addition the coupling between alanine and Na influxes is markedly reduced at pH 2.5. With the exception of H and Li, none of these monovalent cations significantly affects carrier-mediated alanine influx in the absence of Na indicating that their inhibitory effects are largely restricted to the Na-dependent fraction of influx. Increasing H concentration from 0.03 to 3 mM does not affect influx in the absence of Na but markedly inhibits influx in the presence of Na. Li significantly enhances alanine influx in the absence of Na. Ag, UO(2), and La also inhibit the Na-dependent fraction of alanine influx. These findings suggest that anionic groups having a pK(a) of approximately 4 are involved in the interaction between Na and the alanine-carrier complex; present evidence implicates carboxylate groups however, phosphoryl residues cannot be ruled out. The previously proposed kinetic model for the Na-alanine interaction has been extended to accommodate these effects of H and other monovalent cations. The mechanistic and physiological implications of these findings are discussed.


Medication: reasons and interventions for noncompliance.
1. There is a strong correlation between medication noncompliance and higher rates of illness relapse. The causes of noncompliance include side effects, knowledge deficits, and patient/therapist relationships. 2. The nurse's ongoing assessment and understanding of the patients' reasons for treatment resistance is the key to promoting medication compliance. 3. Because compliance requires patients' complete understanding of their illness and their need for medication treatment, patient education is the initial intervention in promoting medication adherence. 4. The patient must no longer be viewed as the guilty party. The promotion of medication compliance must be the responsibility of both the health care professional and the patient.


Segmentally structured disk triboelectric nanogenerator for harvesting rotational mechanical energy.
We introduce an innovative design of a disk triboelectric nanogenerator (TENG) with segmental structures for harvesting rotational mechanical energy. Based on a cyclic in-plane charge separation between the segments that have distinct triboelectric polarities, the disk TENG generates electricity with unique characteristics, which have been studied by conjunction of experimental results with finite element calculations. The role played by the segmentation number is studied for maximizing output. A distinct relationship between the rotation speed and the electrical output has been thoroughly investigated, which not only shows power enhancement at high speed but also illuminates its potential application as a self-powered angular speed sensor. Owing to the nonintermittent and ultrafast rotation-induced charge transfer, the disk TENG has been demonstrated as an efficient power source for instantaneously or even continuously driving electronic devices and/or charging an energy storage unit. This work presents a novel working mode of TENGs and opens up many potential applications of nanogenerators for harvesting even large-scale energy.


Severe Agitation as an Unusual Presentation of Multisystem Inflammatory Syndrome in Children.
Multisystem inflammatory syndrome in children (MIS-C) is a rare hyperinflammatory syndrome that mainly affects children after a primary infection with coronavirus disease 2019 (COVID-19), with the possibility of severe and lethal complications. We report a case of a unique presentation of MIS-C in a four-year-old boy who presented with severe agitation, muscle spasms, and two days of fever. Other findings consistent with MIS-C were revealed later, and he was managed with intravenous immunoglobulin (IVIG) and steroids. He showed a dramatic response of improvement and was discharged. This case report aimed to raise health professionals' awareness about the atypical presentations of MIS-C and the importance of early diagnosis, treatment, and follow-up MIS-C cases to avoid complications affecting children's lives.


Association of HLA-DRB1 gene polymorphisms with hepatocellular carcinoma risk: a meta-analysis.
The study aimed to assess the association between human leukocyte antigen (HLA)-DRB1 allele polymorphisms and hepatocellular carcinoma (HCC) susceptibility. Relevant case-control studies on HLA-DRB1 allele correlation with HCC risk published between 2000 and 2015 were searched and retrieved in literature database. The odds ratio (OR) with its 95% confidence interval (CI) were employed to calculate the strength of association. Total 16 articles including 2208 HCC patients and 3028 relevant controls were finally screened out. A total of 12 case-control studies including 2030 HCC patients and 2817 relevant controls were screened out. Thirteen alleles (HLA-DRB1 *01, *03, *04, *07, *08, *09, *10, *11, *12, *13, *14, *15, and *16) were reported. Overall, we found that HLA-DRB1 *1 and *11 allele polymorphisms were significantly associated with decreased the HCC risk (*1: OR=0.53, 95% CI: 0.29-0.96, P=0.04; *11: OR=0.58, 95% CI: 0.38-0.88, P=0.010); while *12 and *14 allele polymorphisms were significantly associated with increased the HCC risk (*12: OR=1.49, 95% CI: 1.08-2.07, P=0.02; *14: OR=1.89, 95% CI: 1.27-2.82, P=0.002) in a fixed-effect model. However, other HLA-DRB1 allele polymorphisms were not associated with HCC susceptibility (P>0.05). HLA-DRB1 *1 and *11 allele polymorphisms were protective factors, *12 and *14 allele polymorphisms were risk factors for HCC development. Future large-scale studies with more ethnicities are still needed.


Stable Cu Catalysts Supported by Two-dimensional SiO2 with Strong Metal-Support Interaction.
Cu-based catalysts exhibit excellent performance in hydrogenation reactions. However, the poor stability of Cu catalysts under high temperatures has restricted their practical applications. The preparation of stable Cu catalysts supported by SiO2 with strong metal-support interaction (SMSI) has thus aroused great interest due to the high abundance, low toxicity, feasible processability, and low cost of SiO2 . The challenge in the construction of such SMSI remains to be the inertness of SiO2 . Herein, a simple and scalable method is developed to prepare 2D silica (2DSiO2 ) supported Cu catalysts with SMSI by carefully manipulating the topological exfoliation of CaSi2 with CuCl2 and thereafter calcination. The prepared Cu-2DSiO2 catalysts with the unique encapsulated Cu nanoparticles exhibit excellent activity and long-term stability in high-temperature CO2 hydrogenation reactions. This feasible and low-cost solution for stabilizing Cu catalysts might shed light on their realistic applications.


Concentration of antibodies against Porphyromonas gingivalis is increased before the onset of symptoms of rheumatoid arthritis.
The periodontal pathogen Porphyromonas gingivalis is hypothesized to be important in rheumatoid arthritis (RA) aetiology by inducing production of anti-citrullinated protein antibodies (ACPA). We have shown that ACPA precede RA onset by years, and that anti-P. gingivalis antibody levels are elevated in RA patients. The aim of this study was to investigate whether anti-P. gingivalis antibodies pre-date symptom onset and ACPA production. A case-control study (251 cases, 198 controls) was performed within the Biobank of Northern Sweden. Cases had donated blood samples (n = 422) before the onset of RA symptoms by 5.2 (6.2) years (median (interquartile range)). Blood was also collected from 192 RA patients following diagnosis. Antibodies against P. gingivalis virulence factor arginine gingipainB (RgpB), and a citrullinated peptide (CPP3) derived from the P. gingivalis peptidylarginine deiminase enzyme, were analysed by ELISA. Anti-RgpB IgG levels were significantly increased in pre-symptomatic individuals (mean ± SEM; 152.7 ± 14.8 AU/ml) and in RA patients (114.4 ± 16.9 AU/ml), compared with controls (p < 0.001). Anti-CPP3 antibodies were detected in 5 % of pre-symptomatic individuals and in 8 % of RA patients, with elevated levels in both subsets (4.33 ± 0.59 and 9.29 ± 1.81 AU/ml, respectively) compared with controls (p < 0.001). Anti-CPP3 antibodies followed the ACPA response, with increasing concentrations over time, whilst anti-RgpB antibodies were elevated and stable in the pre-symptomatic individuals with a trend towards lower levels after RA diagnosis. Anti-P. gingivalis antibody concentrations were significantly increased in RA patients compared with controls, and were detectable years before onset of symptoms of RA, supporting an aetiological role for P. gingivalis in the development of RA.


Patient satisfaction with primary care: are there differences between the approaches in family and general medicine?
To examine patients' satisfaction with health care services in primary care, and to determine a difference of attitudes towards the work of general and family medicine offices. This descriptive analytical study was conducted among patients of the Primary Health Care Zenica, who had had recent experience with the work of family or general medicine. The questionnaire for the evaluation of general and family medicine by patients was made on the basis of standardized European Project on Patient Evaluation of General Practice Care questionnaires (EUROPEP). Random sampling was used, and the patient population was divided into two clusters: patients treated in general and family practice. Respondents in the offices were selected by simple random sampling. The study included 100 subjects, 50 for general and 50 for family medicine. There were 56 (56.0%) males, and the most common age group was 41-60 years with 42 (42.0%) subjects. Differences in patient satisfaction in favor of family medicine were statistically most significant when it came to scheduling examinations at times convenient to the patient (p=16.28), the possibility of telephone links with the office (p=32.55) and long waiting in waiting room (p=30.42). Collected data confirm the high level of patients' satisfaction with the family medicine units of primary health care. Elaborated EUROPEP questionnaire seems to be a useful tool for the study Key words: satisfaction, health care quality, EUROPEP questionnaire.


Endotoxin tolerance enhances interleukin-10 renal expression and decreases ischemia-reperfusion renal injury in rats.
The potential implication of interleukin (IL) 6, tumor necrosis factor alpha (TNF-alpha), and IL-10 in the protective effect of low-dose lipopolysaccharide (LPS) administration against renal ischemia-reperfusion injury was evaluated in a rat model. Eighteen male Sprague-Dawley rats were injected intravenously with either 0.5 mg/kg of LPS (tolerant group) or saline (control group) 2 days before surgery. Ischemic renal injury was induced by clamping the left renal artery for 60 min on rats immediately after right-side nephrectomy. Reperfusion was obtained by clamp removal and was studied at R0 (no reperfusion), 2H (R2), and 24H (R24) by renal tubular disorder characterization and by plasma creatinine as well as renal cytokine (IL-6, IL-10, and TNF-alpha) studies. No differences were observed between the two groups as concerns the period immediately after renal ischemia (R0). The endotoxin-tolerant group was associated with a significantly lower creatinine level at R24 (231 +/- 28 vs 315 +/- 36 micromol/L; P = 0.007). Pretreatment with LPS significantly reduced the degree of proximal tubule necrosis and outer medulla congestion. In such tolerant animals, renal IL-6 production was decreased, whereas IL-10 production was significantly increased at R2 and R24. There were no differences in TNF-alpha renal production. In this study, we demonstrated that administration of low doses of LPS to rats had a protective effect from renal reperfusion injury, and our data suggest that IL-10 might play a role in this phenomenon.


Detection of Clostridium difficile infection: a suggested laboratory diagnostic algorithm.
Currently, the diagnosis of Clostridium difficile infection (CDI) relies on the detection of toxins A and B in faeces but the sensitivity of these tests has been questioned, particularly in advanced disease. In this context, additional methods to enhance the diagnosis of C. difficile have been investigated. In this study, 1007 faecal samples are tested using toxigenic culture, an immunoassay for toxins AB and the C. difficile-specific glutamate dehydrogenase (GDH) test. Samples positive by any of the above tests are evaluated for the presence of faecal lactoferrin as an indicator of intestinal inflammation. Patients with evidence of inflammation but with negative toxin AB tests are followed up to assess clinical outcome. The toxin AB test was positive in 35 samples (3.4%), while 121 (12%) samples were culture-positive, 87 (8.6%) of which were toxigenic. Glutamate dehydrogenase proved to be a sensitive and specific marker of C. difficile with a negative predictive value of 99.3% (95% CI: 0.98-1.00). Faecal lactoferrin was positive in 52/129 (40.3%) samples tested. A cohort of 15 patients with a negative faecal toxin AB and a positive lactoferrin test was C. difficile culture-positive with a toxigenic isolate; clinically, all had advanced CDI. All demonstrated faecal toxin between five and 41 days later on repeat testing. It is suggested that a two-step algorithm be used to include screening faecal samples for GDH, with positive samples tested for faecal toxin AB and lactoferrin. Patients who present with a negative faecal toxin AB test and a positive lactoferrin test were serially tested for faecal toxin AB every five to seven days until a diagnosis was established. More sensitive tests than enzyme-linked immunosorbent assay (ELISA) for the detection of faecal toxin, or the use of a rapid specific test for the presence of a toxigenic strain, must be considered in such patients.


Accumulation of Scoparone in Heat-Treated Lemon Fruit Inoculated with Penicillium digitatum Sacc.
Phytoalexin scoparone (6,7-dimethoxycoumarin) generally was not detected in noninoculated lemon fruit (Citrus limon [L.] Burm., cv Eureka) but accumulated in fruit after inoculation with Penicillium digitatum Sacc. A much greater increase in the amount of scoparone was found in fruit exhibiting an incompatible response to Penicillium after heat treatment at 36 degrees C for 3 days. Heat treatment prevented development of decay in the inoculated fruit. The concentration of the compound after inoculation continued to increase during and after the heat treatment period, reaching 178 micrograms per gram fresh weight of the flavedo 6 days after the heat treatment. Changes in scoparone concentration in fruit were closely correlated with the changes in the antifungal activity of the fruit extract. A low concentration of the phytoalexin was detected in fruit injured mechanically. Scoparone also accumulated in the fruit following ultraviolet illumination; the concentration of the compound was dose-dependent. Median effective dose values of the inhibition of germ tube elongation and spore germination of P. digitatum were 29 and 46 micrograms per milliliter, respectively. Our findings suggest that the rapid increase in scoparone concentration plays an important role in the increased resistance of heat-treated lemon fruit to infection by P. digitatum.


KDM6A facilitates Xist upregulation at the onset of X inactivation.
X chromosome inactivation (XCI) is a female-specific process in which one X chromosome is silenced to balance X-linked gene expression between the sexes. XCI is initiated in early development by upregulation of the lncRNA Xist on the future inactive X (Xi). A subset of X-linked genes escape silencing and thus have higher expression in females, suggesting female-specific functions. One of these genes is the highly conserved gene Kdm6a , which encodes a histone demethylase that removes methyl groups at H3K27 to facilitate gene expression. Here, we investigate the role of KDM6A in the regulation of Xist . We observed impaired upregulation of Xist during early stages of differentiation in hybrid mouse ES cells following CRISPR/Cas9 knockout of Kdm6a . This is associated with reduced Xist RNA coating of the Xi, suggesting diminished XCI potency. Indeed, Kdm6a knockout results in aberrant overexpression of genes from the Xi after differentiation. KDM6A binds to the Xist promoter and knockout cells show an increase in H3K27me3 at Xist . These results indicate that KDM6A plays a role in the initiation of XCI through histone demethylase-dependent activation of Xist during early differentiation.


Personal characteristics relating to risk of invasive epithelial ovarian cancer in older women in the United States.
The ovarian cancer incidence rate is higher for women over 55 years of age than for younger women, but it increases less rapidly with age after age 55 years than before. This slower rate of increase suggests that the postmenopausal ovary may be less exposed or less susceptible than the functioning one to endogenous or exogenous carcinogens. For example, it is not exposed to mitotic stimuli at follicle rupture, which may increase the likelihood of malignancy. Findings from a collaborative analysis of 12 U.S. case-control studies are used to examine associations between invasive epithelial ovarian cancer and certain reproductive and hormonal characteristics, and to determine if those associations change as women age. Ovarian cancer risk reductions were associated with pregnancy (regardless of outcome), lactation, and oral contraceptive use. The percentage risk reduction associated with pregnancy was smaller for older women than younger women, although the absolute magnitude of the risk reduction increased with age. In contrast, the percentage risk reduction associated with oral contraceptive use was greater for older women. The total duration of ovulation was strongly associated with increased risk in women under 55 years of age, but not in older women. The greater protection to older women associated with oral contraceptive use suggests that the early high-potency contraceptive formulations used by these women may have been more protective than recent ones. The sparsity of strong risk factors in older women emphasizes the need for sensitive and specific markers for early detection of ovarian malignancy in this age group.


Syndrome of developmental retardation, facial and skeletal anomalies, and hyperphosphatasia in two sisters: nosology and genetics of the Coffin-Siris syndrome.
We report on 2 sisters, 3 and 6 years old, with a possible new syndrome consisting of developmental retardation, facial and skeletal anomalies, and hyperphosphatasia. This disorder closely resembles the Coffin-Siris syndrome (McKusick number 135900). We describe the difficulties in achieving a diagnosis. A major diagnostic clue was the radiological recognition of hypoplasia/aplasia of the terminal phalanx of the 5th finger. Minor facial anomalies and mental retardation alone had not led to the proper diagnosis. Still, several diagnostic possibilities remain. For unknown reasons both children have an increased level of serum alkaline phosphatase activity.


The ligaments of the canine hip joint revisited.
Numerous conventional anatomical textbooks describe the canine hip joint, but many contradictions, in particular regarding the ligament of the femoral head, are present. This paper presents a brief overview of the different literature descriptions. These are compared with own observations that have resulted in a revised description of the anatomy of the ligament of the femoral head in the dog. To this purpose, the hip joints of 41 dogs, euthanized for reasons not related to this study and devoid of lesions related to hip joint pathology, were examined. It was observed that the ligament of the femoral head is not a single structure that attaches only to the acetabular fossa, as generally accepted, but it also connects to the transverse acetabular ligament and is complemented by a strong accessory ligament that courses in caudal direction to attach in the elongation of the acetabular notch that extends on the cranioventral surface of the body of the ischium. The description of this accessory ligament in conventional anatomical handbooks is incomplete. This description of the accessory ligament of the femoral head could support the research unravelling the etiopathogenesis of hip instability.


Graph Convolutions on Spectral Embeddings for Cortical Surface Parcellation.
Neuronal cell bodies mostly reside in the cerebral cortex. The study of this thin and highly convoluted surface is essential for understanding how the brain works. The analysis of surface data is, however, challenging due to the high variability of the cortical geometry. This paper presents a novel approach for learning and exploiting surface data directly across multiple surface domains. Current approaches rely on geometrical simplifications, such as spherical inflations, a popular but costly process. For instance, the widely used FreeSurfer takes about 3 hours to parcellate brain surfaces on a standard machine. Direct learning of surface data via graph convolutions would provide a new family of fast algorithms for processing brain surfaces. However, the current limitation of existing state-of-the-art approaches is their inability to compare surface data across different surface domains. Surface bases are indeed incompatible between brain geometries. This paper leverages recent advances in spectral graph matching to transfer surface data across aligned spectral domains. This novel approach enables direct learning of surface data across compatible surface bases. It exploits spectral filters over intrinsic representations of surface neighborhoods. We illustrate the benefits of this approach with an application to brain parcellation. We validate the algorithm over 101 manually labeled brain surfaces. The results show a significant improvement in labeling accuracy over recent Euclidean approaches while gaining a drastic speed improvement over conventional methods.


Triterpenes for Well-Balanced Scar Formation in Superficial Wounds.
Triterpenes are demonstrably effective for accelerating re-epithelialisation of wounds and known to improve scar formation for superficial lesions. Among the variety of triterpenes, betuline is of particular medical interest. Topical betuline gel (TBG) received drug approval in 2016 from the European Commission as the first topical therapeutic agent with the proven clinical benefit of accelerating wound healing. Two self-conducted randomized intra-individual comparison clinical studies with a total of 220 patients involved in TBG treatment of skin graft surgical wounds have been screened for data concerning the aesthetic aspect of wound healing. Three months after surgery wound treatment with TBG resulted in about 30% of cases with more discreet scars, and standard of care in about 10%. Patients themselves appreciate the results of TBG after 3 months even more (about 50%) compared to standard of care (about 10%). One year after surgery, the superiority of TBG counts for about 25% in comparison with about 10%, and from the patients' point of view, for 25% compared to 4% under standard of care. In the majority of wound treatment cases, there is no difference visible between TBG treatment and standard of care after 1 year of scar formation. However, in comparison, TBG still offers a better chance for discreet scars and therefore happens to be superior in good care of wounds.


Operational evaluation of the EXEMSI project. Experimental Campaign for the European Manned Space Infrastructure.
In general the EXEMSI project has proved to be very successful mission. It has demonstrated that it is indeed possible to perform a major and useful project in a short time and on a moderate budget. In addition to achieving the scientific objectives, this simulation project provided valuable experience in the training of members of chamber crew and ground control crew for their tasks. It covered all aspects of a mission from call for experiment proposals, crew selection and training, integration and testing of the facility and its equipment, to daily monitoring and managing of the mission, and finally post-isolation data collection and evaluation. These other activities were accomplished by a small team of experts in the astoundingly short time of 8 months. What was lacking in manpower, time and funds, was more than made up for by enthusiasm, expertise, team spirit, hard work and long hours well beyond the call of duty of all those involved. In addition to the specific and technological objectives reached, many lessons learned in this operation have been identified, which could help to improve future missions. The experience has shown pitfalls to be avoided in future mission, as well as points where some small increase in effort can make a considerable difference. With the prospect of long-term manned spaceflights looming in the near future and the ever increasing costs of such endeavors, the possibilities offered by running simulated missions on the ground should be seriously considered. Such simulations permit the study of scientific and operational aspects of a space mission prior to its actual implementation. A ground based simulation of an extended space mission may be run at a fraction of the cost of an in-orbit precursor mission of even one-week duration. However, careful planning of the simulation mission is required so that it may yield relevant information and useful experience. Lessons learned from the EXEMSI project should be taken into account in such planning. At the start clear goals should be formulated, that can provide clear guidelines for building up the infrastructure and defining the operational scenario. A long duration mission simulating the conditions on the Russian space station MIR could provide a valuable source of information and experience in preparing for the MIR '95 Mission.


Value of dynamometry in assessing upper extremity function in children with myelomeningocele.
Children with myelodysplasia frequently have abnormal hand function. Etiologies include brainstem and cervical cord compression due to the Chiari II malformation, syringomyelia, hydrocephalus, and cerebral dysmorphism. Determination of potentially correctable causes of hand dysfunction may be difficult. We describe the use of the Jaymar dynamometer for assessing grip strength as a means of detecting early changes in hand function.


Efficacy evaluation of imatinib treatment in patients with gastrointestinal stromal tumors: a meta-analysis.
To perform a meta-analysis to derive a more precise estimation of imatinib treatment for different genotypes of gastrointestinal stromal tumors (GIST). Studies were identified by searching PubMed and Embase. Inclusive criteria were patients with exon 9-mutant, exon 11-mutant or wide type (WT) GIST, receiving chemotherapy of imatinib for clinical trial, and efficacy evaluation was cumulative response (CR) including complete response and partial response. The odds ratios (OR) for CR in stem cell factor receptor (KIT) mutation patients vs WT genotype patients, KIT exon 11-mutant genotype patients vs KIT exon 9-mutant genotype patients and KIT exon 9-mutant genotype patients vs WT genotype patients were calculated with 95% confidence interval (CI) for each study as an estimation of the efficacy of imatinib. Five studies including 927 patients were involved in this meta-analysis. The overall OR (KIT group vs WT group) was 3.34 (95% CI: 2.30-4.86, P < 0.00001, P(heterogeneity) = 0.04). The overall OR in KIT exon 11 group vs KIT exon 9 group was 3.29 (95% CI: 2.17-5.00, P < 0.00001, P(heterogeneity) = 0.33). The overall OR in KIT exon 9 group vs WT group was 1.23 (95% CI: 0.73-2.10, P = 0.44, P(heterogeneity) = 0.42). Most patients with different genotypes of GIST and KIT exon 11-mutant will benefit from the individualized treatment of imatinib.


Factor structure of the Wechsler Adult Intelligence Scale-III in schizophrenia.
This report examines and compares the factor structure of the new edition of the Wechsler Adult Intelligence Scale (WAIS-III) in a sample of chronic schizophrenia and schizoaffective disorder outpatients (n = 120) and an age-matched sample of individuals drawn from the WAIS-III standardization sample (n = 200). Exploratory and confirmatory factor analyses similar to those reported by the developers of the scale suggested that a model of WAIS-III performance with correlated factors for verbal comprehension, perceptual organization, working memory, and processing speed fit the data from the schizophrenia sample as well as it fit the nonclinical comparison sample and fit the data from both samples better than alternative models.


The Depths of Despair Among US Adults Entering Midlife.
To test whether indicators of despair are rising among US adults as they age toward midlife and whether this rise is concentrated among low-educated Whites and in rural areas. We used data from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative study of US adolescents in 1994. Our sample was restricted to individuals who participated in 1 or more of 5 waves (1994-2017) and self-identified as non-Hispanic White, non-Hispanic Black, or Hispanic (n = 18 446). We examined change in indicators of despair from adolescence to adulthood using multilevel regression analysis, testing for differences by race/ethnicity, education, and rurality. We found evidence of rising despair among this cohort over the past decade. This increase was not restricted to low-educated Whites or to rural areas. Results suggest that generally rising despair among the young adult cohort now reaching midlife that cuts across racial/ethnic, educational, and geographic groups may presage rising midlife mortality for these subgroups in the next decade.


Cold hemagglutination pathophysiology. Evaluation and management of patients undergoing cardiac surgery with induced hypothermia.
The widespread induction of systemic hypothermia and use of iced cardioplegic solutions in cardiac surgery may promote occasional cold autoagglutination. Routine laboratory methods used to detect cold-agglutinating autoantibodies may not take into account the extremely low temperatures that the heart and body may attain during cardiopulmonary bypass. Several cold-mediated complications have now been encountered during cardiac surgery in patients with both known and unsuspected cold-reactive autoantibodies. This review will provide the clinician with a working knowledge of the cold autoimmune disorders, a rapid method for differential diagnosis in unproved cases, and an ability to select techniques for reliable myocardial and renal protection in both known and unsuspected cases.


Methadone adverse reaction presenting with large increase in plasma methadone binding: a case series.
The use of methadone as an analgesic is on the increase, but it is widely recognized that the goal of predictable and reproducible dosing is confounded by considerable variability in methadone pharmacokinetics, and unpredictable side effects that include sedation, respiratory depression and cardiac arrhythmias. The mechanisms underlying these unpredictable effects are frequently unclear. Here, to the best of our knowledge we present the first report of an association between accidental methadone overexposure and increased plasma protein binding, a new potential mechanism for drug interactions with methadone. We describe here the cases of two patients who experienced markedly different responses to the same dose of methadone during co-administration of letrozole. Both patients were post-menopausal Caucasian women who were among healthy volunteers participating in a clinical trial. Under the trial protocol both patients received 6 mg of intravenous methadone before and then after taking letrozole for seven days. One woman (aged 59) experienced symptoms consistent with opiate overexposure after the second dose of methadone that were reversed by naloxone, while the other (aged 49) did not. To understand the etiology of this event, we measured methadone pharmacokinetics in both patients. In our affected patient only, a fourfold to eightfold increase in methadone plasma concentrations after letrozole treatment was observed. Detailed pharmacokinetic analysis indicated no change in metabolism or renal elimination in our patient, but the percentage of unbound methadone in the plasma decreased 3.7-fold. As a result, the volume of distribution of methadone decreased approximately fourfold. The increased plasma binding in our affected patient was consistent with observed increases in plasma protein concentrations. The marked increase in the total plasma methadone concentration observed in our patient, and the enhanced pharmacodynamic effect, appear primarily due to a reduced volume of distribution. The extent of plasma methadone binding may help to explain the unpredictability of its pharmacokinetics. Changes in volume of distribution due to plasma binding may represent important causes of clinically meaningful drug interactions.


Peds PLACE: quality continuing medical education in Arkansas.
The University of Arkansas for Medical Sciences (UAMS) and Arkansas Children's Hospital (ACH) sponsor Peds PLACE (Pediatric Physician Learning and Collaborative Education), a telemedicine continuing education program. This study assessed to what extent participants were satisfied with Peds PLACE and how to improve it. It was found that 95% of the participants agreed that the presentations related to their professional needs and 98% that it increased their knowledge. In addition, 81% evaluated the presentations as some of the best they have attended and 93% agreed that the information would translate into professional practice and enhance patient care. Comments were positive and correlated with the survey data. Participants recommended several ways to improve Peds PLACE.


Family well-being concerns of grandparents in skipped generation families.
This study examined the family well-being concerns of grandparents in skipped-generation families. Co-resident grandparents who are responsible for raising their grandchildren completed surveys, focus groups, or individual interviews. Service providers to skipped-generation families also participated in individual interviews to provide an additional perspective to grandparents' concerns. Results indicated 5 levels of concerns: intrapersonal, interpersonal, organizational or institutional, policy, and societal. Concerns at different levels were interrelated and pointed to the need for multilevel interventions to help these families. Implications of the findings for future interventions with skipped-generation families are discussed.


New onset autoimmune diabetes mellitus and hypothyroidism secondary to pembrolizumab in a patient with metastatic lung cancer.
Immunotherapy has become an important pillar for the management of advanced cancer. Immune-related adverse events including endocrinopathies have been well described with programmed cell death 1 inhibitors such as pembrolizumab. While thyroid dysfunction is the most common endocrinopathy associated with pembrolizumab, new-onset autoimmune diabetes mellitus (DM) is extremely rare. The authors report a case of pembrolizumab-induced primary hypothyroidism and type 1 diabetes mellitus presenting with diabetic ketoacidosis (DKA). A 59-year-old female patient was treated with pembrolizumab for a stage 4 lung adenocarcinoma. She presented to the emergency department with hyperglycaemia-related signs and symptoms, such as polyuria, polydipsia, weight loss, vomiting, asthenia and dehydration, 3 weeks after her first dose of pembrolizumab. Laboratory evaluation revealed hyperglycaemia, hyperketonaemia and high anion gap metabolic acidaemia consistent with DKA. After prompt and adequate treatment of DKA, she transitioned to s.c. basal-bolus insulin. The diagnose of autoimmune DM was established based on the undetectable C-peptide levels and seropositivity for antiglutamic acid decarboxylase antibodies. Additional hormonal parameters revealed overt hypothyroidism and levothyroxine therapy was initiated. This case highlights the importance of blood glucose and thyroid function monitoring as an integral part of cancer treatment protocols for pembrolizumab and other immune checkpoint inhibitors. Programmed cell death 1 (PD1) inhibitors such as pembrolizumab can cause endocrine immune-related adverse events (irAE), including thyroid dysfunction and type 1 diabetes mellitus (T1DM). Thyroid dysfunction is the most frequent endocrine irAE secondary to PD1 inhibitors. Autoimmune diabetes and possible resultant diabetic ketoacidosis are rare, but life-threatening adverse events associated with pembrolizumab. Pembrolizumab-induced T1DM often present with relatively low HbAlc levels, reflecting the fulminant onset of β-cell destruction. Patients treated with pembrolizumab and other immune checkpoints inhibitors should be monitored regularly for hyperglycaemia and thyroid dysfunction.


Leukotriene A4 hydrolase, mutation of tyrosine 378 allows conversion of leukotriene A4 into an isomer of leukotriene B4.
Leukotriene A4 hydrolase catalyzes the final step in the biosynthesis of the proinflammatory compound leukotriene B4, a reaction which is accompanied by suicide inactivation of the enzyme by leukotriene A4. We have recently reported that Tyr-378 is a major structural determinant for suicide inactivation and that mutation of Tyr-378 into Phe or Gln protects leukotriene A4 hydrolase from this catalytic restriction (Mueller, M. J., Blomster, M., Opperman, U. C. T., Jörnvall, H., Samuelsson, B., and Haeggström, J. Z. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 5931-5935). In the present study, we show that both [Y378F]- and [Y378Q]leukotriene A4 hydrolase converts leukotriene A4 not only into leukotriene B4 but also into a second, previously unknown, product of the enzyme. From biophysical analyses and comparison with a synthetic standard, the structure of this product was determined to 5S,12R-dihydroxy-6,10-trans-8, 14-cis-eicosatetraenoic acid, i.e. Delta6-trans-Delta8-cis-leukotriene B4. The relative formation of Delta6-trans-Delta8-cis-leukotriene B4 versus leukotriene B4 by [Y378F]- and [Y378Q]leukotriene A4 hydrolase, was 18% and 32%, respectively. For [Y378F]leukotriene A4 hydrolase, the turnover of leukotriene A4 into leukotriene B4 or Delta6-trans-Delta8-cis-leukotriene B4 was calculated to 2.5 s-1 which is almost three times the kcat value of the wild type enzyme. Taken together, these findings indicate that Tyr-378 is located at the active site where it assists in the formation of the correct double-bond geometry in the product leukotriene B4.


Evolution of a cross-feeding interaction following a key innovation in a long-term evolution experiment with Escherichia coli.
The evolution of a novel trait can profoundly change an organism's effects on its environment, which can in turn affect the further evolution of that organism and any coexisting organisms. We examine these effects and feedbacks following the evolution of a novel function in the Long-Term Evolution Experiment (LTEE) with Escherichia coli. A characteristic feature of E. coli is its inability to grow aerobically on citrate (Cit-). Nonetheless, a Cit+ variant with this capacity evolved in one LTEE population after 31 000 generations. The Cit+ clade then coexisted stably with another clade that retained the ancestral Cit- phenotype. This coexistence was shaped by the evolution of a cross-feeding relationship based on C4-dicarboxylic acids, particularly succinate, fumarate, and malate, that the Cit+ variants release into the medium. Both the Cit- and Cit+ cells evolved to grow on these excreted resources. The evolution of aerobic growth on citrate thus led to a transition from an ecosystem based on a single limiting resource, glucose, to one with at least five resources that were either shared or partitioned between the two coexisting clades. Our findings show that evolutionary novelties can change environmental conditions in ways that facilitate diversity by altering ecosystem structure and the evolutionary trajectories of coexisting lineages.


An empirical typology of social networks and its association with physical and mental health: a study with older Korean immigrants.
In the context of social convoy theory, the purposes of the study were (a) to identify an empirical typology of the social networks evident in older Korean immigrants and (b) to examine its association with self-rated health and depressive symptoms. The sample consisted of 1,092 community-dwelling older Korean immigrants in Florida and New York. Latent class analyses were conducted to identify the optimal social network typology based on 8 indicators of interpersonal relationships and activities. Bivariate and multivariate analyses were conducted to examine how the identified social network typology was associated with self-rating of health and depressive symptoms. Results from the latent class analysis identified 6 clusters as being most optimal, and they were named diverse, unmarried/diverse, married/coresidence, family focused, unmarried/restricted, and restricted. Memberships in the clusters of diverse and married/coresidence were significantly associated with more favorable ratings of health and lower levels of depressive symptoms. Notably, no distinct network solely composed of friends was identified in the present sample of older immigrants; this may reflect the disruptions in social convoys caused by immigration. The findings of this study promote our understanding of the unique patterns of social connectedness in older immigrants.


Stroke case fatality in sub-Saharan Africa: Systematic review and meta-analysis.
The burden of stroke is high in sub-Saharan Africa; however, few data are available on long-term mortality. To estimate over one-month stroke case fatality in sub-Saharan Africa. A systematic review and meta-analysis were performed according to meta-analysis of observational studies in epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO protocol: CRD42020192439), on five electronic databases (PubMed, Science direct, AJOL, EMBASE, and Web of Sciences). We searched all studies on stroke case fatality over one month in sub-Saharan Africa published between 1st January 2000 and 31st December 2019. We included 91 studies with a total of 34,362 stroke cases. The one-month pooled stroke case-fatality rate was 24.1% [95% CI: 21.5-27.0] and 33.2% [95% CI: 23.6-44.5] at one year. At three and five years, the case-fatality rates were respectively 40.1% [95% CI: 20.8-63.0] and 39.4% [95% CI: 14.3-71.5] with high heterogeneity. Hemorrhagic stroke was associated with a higher risk of mortality at one month, but ischemic stroke increased the risk of mortality over six months. Diabetes was associated with poor prognosis at 6 and 12 months with odds ratios of 1.64 [95% CI: 1.22-2.20] and 1.85 [1.25-2.75], respectively. The stroke case fatality over one month was very high, compared to case fatalities reported in Western countries and can be explained by a weak healthcare systems and vascular risk factors.


Coronary computed tomography angiography for early triage of patients with acute chest pain: the ROMICAT (Rule Out Myocardial Infarction using Computer Assisted Tomography) trial.
This study was designed to determine the usefulness of coronary computed tomography angiography (CTA) in patients with acute chest pain. Triage of chest pain patients in the emergency department remains challenging. We used an observational cohort study in chest pain patients with normal initial troponin and nonischemic electrocardiogram. A 64-slice coronary CTA was performed before admission to detect coronary plaque and stenosis (>50% luminal narrowing). Results were not disclosed. End points were acute coronary syndrome (ACS) during index hospitalization and major adverse cardiac events during 6-month follow-up. Among 368 patients (mean age 53 +/- 12 years, 61% men), 31 had ACS (8%). By coronary CTA, 50% of these patients were free of coronary artery disease (CAD), 31% had nonobstructive disease, and 19% had inconclusive or positive computed tomography for significant stenosis. Sensitivity and negative predictive value for ACS were 100% (n = 183 of 368; 95% confidence interval [CI]: 98% to 100%) and 100% (95% CI: 89% to 100%), respectively, with the absence of CAD and 77% (95% CI: 59% to 90%) and 98% (n = 300 of 368, 95% CI: 95% to 99%), respectively, with significant stenosis by coronary CTA. Specificity of presence of plaque and stenosis for ACS were 54% (95% CI: 49% to 60%) and 87% (95% CI: 83% to 90%), respectively. Only 1 ACS occurred in the absence of calcified plaque. Both the extent of coronary plaque and presence of stenosis predicted ACS independently and incrementally to Thrombolysis In Myocardial Infarction risk score (area under curve: 0.88, 0.82, vs. 0.63, respectively; all p < 0.0001). Fifty percent of patients with acute chest pain and low to intermediate likelihood of ACS were free of CAD by computed tomography and had no ACS. Given the large number of such patients, early coronary CTA may significantly improve patient management in the emergency department.


CCR6 ligands inhibit HIV by inducing APOBEC3G.
We have identified a post-entry CCR6-dependent mechanism of inhibition of HIV occurring at an early stage of infection mediated by the induction of the host restriction factor apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G). We observed induction of APOBEC3G expression only in CCR6(+) cells but not in cells treated with the G inhibitory (Gi) pathway inhibitor pertussis toxin. CCR6 is highly expressed on peripheral blood CD4(+)CCR5(+) memory T cells and by 2 populations of CD4(+) T cells within the gut, alpha4beta7(+) and T helper type 17, that have been implicated in cell-to-cell spread of HIV and enhanced restoration of CD4(+) T cells within gut-associated lymphoid tissue, respectively. This novel CCR6-mediated mechanism of inhibition allows the identification of pathways that induce intrinsic immunity to HIV, which could be useful in devising novel therapeutics that selectively target CCR6(+) cells.


Doxorubicin/paclitaxel combination chemotherapy for metastatic breast cancer: the Eastern Cooperative Oncology Group experience.
The addition of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to the therapeutic armamentarium for breast cancer has resulted in novel opportunities and challenges for the clinician. In a series of trials that began in 1992, the Eastern Cooperative Oncology Group (ECOG) investigated the role of paclitaxel in combination with doxorubicin for the treatment of patients with advanced breast cancer. The design of the first trial, a limited-institution pilot study, involved alternating doxorubicin and paclitaxel as single agents. The alternating schedule was well tolerated and associated with objective responses in seven of 12 patients entered into the trial. In the second trial, a limited-institution phase I trial, bolus doxorubicin was combined with paclitaxel administered over a 24-hour infusion, with administration of the two drugs separated by 4 hours. While no dose-limiting toxicity was seen at doses of 50 and 150 mg/m2 of doxorubicin and paclitaxel, respectively, dose-limiting mucositis occurred at respective doses of 60 and 175 mg/m2. Mucositis was more common when administration of paclitaxel preceded that of doxorubicin than when doxorubicin preceded paclitaxel. Based on these results, the ECOG initiated a phase III trial comparing single-agent paclitaxel, single-agent doxorubicin, and the combination of paclitaxel and doxorubicin. This study, now an Intergroup trial of ECOG, the Southwest Oncology Group, and the North Central Cancer Treatment Group, is designed to accrue 730 patients. This trial will close to accrual in September 1995, and analysis of the trial should provide useful information regarding the potential synergy of doxorubicin and paclitaxel, the degree of cross-resistance between the two compounds, and the relationship between steady-state paclitaxel levels and response to therapy. In addition, ECOG is currently conducting a trial designed to confirm the striking activity of cisplatin and paclitaxel seen in the British Columbia trials. Future trials by the group will examine means of combining paclitaxel with other active agents.


Pre-surgical mapping of eloquent cortex for paediatric epilepsy surgery candidates: Evidence from a review of advanced functional neuroimaging.
A review of all published evidence for mapping eloquent (motor, language and memory) cortex using advanced functional neuroimaging (functional magnetic resonance imaging [fMRI] and magnetoencephalography [MEG]) for paediatric epilepsy surgery candidates has not been conducted previously. Research in this area has predominantly been in adult populations and applicability of these techniques to paediatric populations is less established. A review was performed using an advanced systematic search and retrieval of all published papers examining the use of functional neuroimaging for paediatric epilepsy surgery candidates. Of the 2724 papers retrieved, 34 met the inclusion criteria. Total paediatric participants identified were 353 with an age range of 5 months-19 years. Sample sizes and comparisons with alternative investigations to validate techniques are small and variable paradigms are used. Sensitivity 0.72 (95% CI 0.52-0.86) and specificity 0.60 (95% CI 0.35-0.92) values with a Positive Predictive Value of 74% (95% CI 61-87) and a Negative Predictive Value of 65% (95% CI 52-78) for fMRI language lateralisation with validation, were obtained. Retrieved studies indicate evidence that both fMRI and MEG are able to provide information lateralising and localising motor and language functions. A striking finding of the review is the paucity of studies (n=34) focusing on the paediatric epilepsy surgery population. For children, it remains unclear which language and memory paradigms produce optimal activation and how these should be quantified in a statistically robust manner. Consensus needs to be achieved for statistical analyses and the uniformity and yield of language, motor and memory paradigms. Larger scale studies are required to produce patient series data which clinicians may refer to interpret results objectively. If functional imaging techniques are to be the viable alternative for pre-surgical mapping of eloquent cortex for children, paradigms and analyses demonstrating concordance with independent measures must be developed.


Survivability and fitness cost of heterogeneous vancomycin-intermediate Staphylococcus aureus.
The aim of this study was to observe the survivability and fitness cost of heterogeneous vancomycin-intermediate Staphylococcus aureus(hVISA) isolates. Survivability study was performed on dry cotton swab, and fitness cost was evaluated by estimating growth kinetics and generation time constant in BACTEC automated system. Total mean maximum time of recovery on primary culture was 4.1 and 7.1 weeks (P = 0.0001) for hVISA and vancomycin-sensitive S. aureus (VSSA), respectively, in dry starved condition. No significant difference between the mean value of lag phase duration (P = 0.89) was noted between hVISA and VSSA isolate in growth kinetics. However, we observed lesser generation time of hVISA isolates compared to S. aureus ATCC 29213 (P = 0.0076). This study concluded that a significant difference in generation time between VSSA and hVISA and suggests that hVISA have fitness cost compared to VSSA. However, further studies with more cases are required.


Regulation of insulin-like growth factor-I expression in mouse preadipocyte Ob1771 cells.
In mouse preadipocyte Ob1771 cells, transcription of the insulin-like growth factor-I (IGF-I) gene was stimulated by growth hormone (GH), and IGF-I protein combined with GH in medium was required for their differentiation to adipocytes. During induction of the differentiation, the intracellular expression of each class of IGF-I mRNA was analyzed by reverse transcriptase-polymerase chain reaction. When the cells were cultured in the presence of GH, the class 1del. IGF-I mRNA was a major molecular species among IGF-I mRNAs. In the presence of both GH and IGF-I, the splicing pattern of IGF-I mRNA changed from class 1del. to class 1. Moreover, as detected by Western blotting, the IGF-I protein was present in cells and in the medium only when the cells were cultured in the presence of both GH and IGF-I. We found that IGF-I secreted from Ob1771 cells could act in an autocrine/paracrine fashion and induce the differentiation of other Ob1771 cells. It was demonstrated that the translation efficiency of class 1 mRNA was higher than that of class 1del. mRNA in vitro. These results suggested that stimulation with exogenous IGF-I in the presence of GH was required for the production of class 1 IGF-I mRNA and that the production of the IGF-I protein was activated by increasing the translation efficiency through shifting the splicing pattern of IGF-I mRNA from class 1del. to class 1. Exogenous IGF-I triggered the differentiation by initiating the synthesis of endogenous IGF-I.


Viral mHealth.
Thousands of mHealth applications are developed every year, but few of these spread or 'go viral'. Even clinical applications that provide health benefits and social value often linger after an initial pilot phase. An examination of common hindrances in low-income countries suggests that more subsidies and education of health care personnel are insufficient solutions. Instead we propose better a priori screening of mHealth applications based on four criteria that may largely determine whether an mHealth application will spread. Further, we illustrate how using these criteria forms a good basis for involving 'impact investors' in the development of mHealth applications. This can reduce risks for public health care providers and increase the likelihood of success.


HPLC/ESI-MSn and ESI-MS studies on the Aconitum alkaloids in three Chinese medicinal herbs.
Aconitum lipo-alkaloids (LDAs) peaks in the previous HPLC studies have shown overlapping behavior, making it impossible to identify the total retention behavior of LDAs. The structural diversity of LDAs in Radix Aconiti, Radix Aconiti Kusnezoffii and Radix Aconiti Lateralis Preparata makes it difficult to synthesize and quantify each of them. Therefore, this study has been devoted to develop a HPLC/ESI-MS(n) method with good resolution of Aconitum alkaloids especially LDAs and then set up a fast ESI-MS SIM method to quantify the total contents of specific skeleton LDAs in the three herbs via in-source CID and the capability of mass separation. As a result, the retention behavior of LDAs was summarized based on an optimized chromatographic separation; 32 alkaloids from the three herbs of Aconitum genus were separated and identified according to their fragmentation pathways by using HPLC/ESI-MS(n). In addition, a fast quantitative analysis ESI-MS SIM method was successfully applied to the quantification of the total contents of specific skeleton LDAs in the three herbs.


Performance measurement for community health services: opportunities and challenges.
This paper presents findings from a study that investigated performance measurement for primary health care services delivered by the community health sector, and assessed the effectiveness and value of a performance measurement approach in the evaluation of these services. Eleven semi-structured interviews were conducted with key stakeholders in South Australia. The findings indicate that three major steps are needed to move forward in the use of performance measurement in the community health sector. These steps are i) development of a policy and strategy statement for community health, ii) identification of performance domains and indicators, and iii) development of appropriate data systems.


Y-splitting with recession of lateral rectus versus lateral rectus recession in correcting upshoot in Duane retraction syndrome.
To report the surgical effect in upshoot of Duane retraction syndrome (DRS) with corecession of horizontal rectus muscles with or without Y-splitting. A retrospective chart review of six patients of DRS received muscle surgeries for upshoot in adducted position was performed. From 1994 to 2010, six Duane patients received muscle surgeries for upshoots of lesion eye in adduction. Their age of receiving surgery ranged from 5 to 41 years. Four of the patients were male, and five had their left eye involved. Three underwent recession of ipsilateral medial and lateral rectus (LR) muscles, and the other three also received Y-splitting of LR muscle when recession. One of the patients that received Y-splitting showed mild hypertropia at down gaze postoperatively, and another one had little improvement of exotropia at the primary position. All patients showed improvement of their upshoots and lid fissure narrowing in adduction as well as face turn. Postoperative improvements in abnormal head posture and upshoots were achieved with corecession of horizontal muscles with or without Y-splitting. Although Y-splitting of the LR muscle is an effective surgery, it might cause undesired complications.


Differential modulation of valence and arousal in high-alexithymic and low-alexithymic individuals.
High-alexithymic individuals are characterized by an impaired ability to identify and communicate emotions whereas low-alexithymic individuals have a wide-ranging ability to deal with emotions. This study examined the hypothesis that valence and arousal modifications of emotional stimuli differentially modulate cortical regions in high-alexithymic and low-alexithymic individuals. To this end, 28 high-alexithymic and 25 low-alexithymic individuals were investigated with event-related fMRI using visual emotional stimuli. We found differential neural activations in the dorsal anterior cingulate, the insula and the amygdala. We suggest that these differences may account for the impaired ability of high-alexithymic individuals to appropriately handle emotional stimuli.


Modification of the pulmonary connective tissue developmental response in the neonatal rat by ciclosporin.
Neonatal rat pups were treated either with ciclosporin at 10 mg/kg/day dissolved in olive oil (experimental) or with pure olive oil (control). Lung protein biosynthesis was evaluated in a protocol which involved the measurement of total accumulated protein, collagen and elastin. Four time points were studied in the first 21 days of life, 12 animals contributing to each point (6 control and 6 ciclosporin). Ciclosporin levels in the treated group ranged widely (2,000-4,000 ng/ml). There were significant differences in total body weight and lung weight in treated vs. controls during and after the first week. DNA contents per unit wet weight varied significantly during the second week of life, indicating increased cellularity of the ciclosporin-treated animals. Associated with this was an increase in the lung protein/DNA ratio as well as the elastin/DNA ratio in the control animals, but not in the treated ones. The lung collagen/DNA ratio was not as dramatically affected by the ciclosporin treatment. However, the collagen content per unit wet weight of lung tissue was increased in the ciclosporin-treated animals at 15 days of life. We conclude that ciclosporin has a marked effect on lung connective tissue metabolism in early life, the long-term effects of which are unappreciated and undocumented but may well be of vital importance in the lungs of long-surviving organ transplant patients.


Evaluation of the effects of electrical stimulation on cartilage repair in adult male rats.
This study describes the organization of mature hyaline xiphoid cartilage during repair in animals submitted to electrical current stimulation. Twenty male Wistar rats, 90 days old, were divided into a control group (CG) and a treated group (TG). A cylindrical full-thickness cartilage defects were created with a 3-mm punch in anesthetized animals. After 24h, TG received daily applications of a continuous electrical current (1Hz/20μA) for 5min. The animals were sacrificed after 7, 21 and 35 days for structural analysis. In CG, the repair tissue presented fibrous characteristics, with fibroblastic cells being infiltrated and permeated by blood vessels. Basophilic foci of cartilage tissue were observed on day 35. In TG, the repair tissue also presented fibrous characteristics, but a larger number of thick collagen fibers were seen on day 21. A large number of cartilaginous nests were observed on day 35. Cell numbers were significantly higher in TG. Calcification points were detected in TG on day 35. There was no difference in elastic fibers between groups. Ultrastructural analysis revealed the presence of chondrocyte-like cells in CG at all time points, but only on days 21 and 35 in TG. The amount of cuprolinic blue-stained proteoglycans was higher in TG on day 35. Microcurrent stimulation accelerates the repair process in non-articular hyaline cartilage.


Electronic State Unfolding for Plane Waves: Energy Bands, Fermi Surfaces, and Spectral Functions.
Present day computing facilities allow for first-principles density functional theory studies of complex physical and chemical phenomena. Often such calculations are linked to large supercells to adequately model the desired property. However, supercells are associated with small Brillouin zones in the reciprocal space, leading to folded electronic eigenstates that make the analysis and interpretation extremely challenging. Various techniques have been proposed and developed to reconstruct the electronic band structures of super cells unfolded into the reciprocal space of an ideal primitive cell. Here we propose an unfolding scheme embedded directly in the Vienna Ab initio Simulation Package (VASP) that requires modest computational resources and allows for an automatized mapping from the reciprocal space of the supercell to the primitive cell Brillouin zone. This algorithm can compute band structures, Fermi surfaces, and spectral functions by using an integrated postprocessing tool (bands4vasp). Here the method is applied to a selected variety of complex physical situations: the effect of doping on the band dispersion in the BaFe2(1-x)Ru2x As2 superconductor, the interaction between adsorbates and polaronic states on the TiO2(110) surface, and the band splitting induced by noncollinear spin fluctuations in EuCd2As2.


Aberrant Amplitude of Low-Frequency Fluctuation and Degree Centrality within the Default Mode Network in Patients with Vascular Mild Cognitive Impairment.
This study aimed to investigate whole-brain spontaneous activities changes in patients with vascular mild cognitive impairment (VaMCI), and to evaluate the relationships between these brain alterations and their neuropsychological assessments. Thirty-one patients with VaMCI and thirty-one healthy controls (HCs) underwent structural MRI and resting-state functional MRI (rs-fMRI) and neuropsychological assessments. The functional alterations were determined by the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC). The gray matter volume (GMV) changes were analyzed using voxel-based morphometry (VBM). Linear regression analysis was used to evaluate the relationships between the structural and functional changes of brain regions and neuropsychological assessments. The VaMCI group had significantly lower scores in the Montreal Cognitive Assessment (MoCA), and higher scores on the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). Compared to the HCs, the VaMCI group exhibited GM atrophy in the right precentral gyrus (PreCG) and right inferior temporal gyrus (ITG). VaMCI patients further exhibited significantly decreased brain activity within the default mode network (DMN), including the bilateral precuneus (PCu), angular gyrus (AG), and medial frontal gyrus (medFG). Linear regression analysis revealed that the decreased ALFF was independently associated with lower MoCA scores, and the GM atrophy was independently associated with higher HAMD scores. The current finding suggested that aberrant spontaneous brain activity in the DMN might subserve as a potential biomarker of VaMCI, which may highlight the underlying mechanism of cognitive decline in cerebral small vessel disease.