Decrease of peripheral resistance after intraoperative administration of iloprost in patients with and without type 2 diabetes mellitus and with peripheral arterial occlusive disease.
In many cases, Ilomedin® infusions are applied as part of a perioperative measure in patients with peripheral arterial occlusive disease because it makes a relevant vasodilatatory effect in patients with type 2 diabetes mellitus and with/without peripheral neuropathy. A prospective case-control study was performed to investigate the effect of prostanoids on peripheral resistance in patients with type 2 diabetes mellitus and patients without type 2 diabetes mellitus, as well as the role of peripheral neuropathy in patients undergoing arterial reconstruction. Sixty patients undergoing arterial reconstruction were enrolled. Sufficient data were collected on 38 patients. Prior to surgery, peripheral nerve conduction velocity was measured. Blood flow volume at the common femoral artery was assessed intraoperatively using a Doppler flowmeter at four time points: at baseline before arterial reconstruction (T0), after reconstruction (T1), after 5 (T2) and 10 min (T3) after intra-arterial application of 3000 ng of Ilomedin. Peripheral resistance units were calculated as a function of mean arterial pressure and flow volume using the following formula: peripheral resistance unit = mean arterial pressure (mm Hg) / flow volume (mL/min). Ilomedin produced an immediate and significant drop of peripheral resistance in patients without type 2 diabetes mellitus as well as in patients with type 2 diabetes mellitus. Patients with peripheral neuropathy showed a less pronounced effect to Ilomedin compared to individuals with normal nerve conduction velocity.


Right Ventricular Limitation: A Tale of Two Elastances.
Right ventricular (RV) dysfunction is a commonly considered cause of low cardiac output in critically ill patients. Its management can be difficult and requires an understanding of how the RV limits cardiac output. We explain that RV stroke output is caught between the passive elastance of the RV walls during diastolic filling and the active elastance produced by the RV in systole. These two elastances limit RV filling and stroke volume and consequently limit left ventricular stroke volume. We emphasize the use of the term "RV limitation" and argue that limitation of RV filling is the primary pathophysiological process by which the RV causes hemodynamic instability. Importantly, RV limitation can be present even when RV function is normal. We use the term "RV dysfunction" to indicate that RV end-systolic elastance is depressed or diastolic elastance is increased. When RV dysfunction is present, RV limitation occurs at lowerpulmonary valve opening pressures and lower stroke volume, but stroke volume and cardiac output still can be maintained until RV filling is limited. We use the term "RV failure" to indicate the condition in which RV output is insufficient for tissue needs. We discuss the physiological underpinnings of these terms and implications for clinical management.


Report on envenomation by a Gila monster (Heloderma suspectum) with a discussion of venom apparatus, clinical findings, and treatment.
Human envenomations by Heloderma species are a rare but clinically important medical problem. We report a case of an adult male bitten on the left hand by a 50-cm male, captive specimen of Heloderma suspectum (Gila monster). Immediate signs and symptoms included pain at the bite site radiating into the arm and axilla and swelling of the hand and forearm. Systemic complaints of nausea, diaphoresis, and dizziness (without a decrease in blood pressure) lasted approximately 1 hour, and laboratory studies were normal. The patient's course was uneventful except for persistent hyperesthesia, which eventually abated. Two types of helodermatid bites produce distinct clinical pictures. The chewing bite potentially causes more envenomation than the slashing bite. The venom contains a number of protein and nonprotein components including serotonin, a bradykinin-releasing substance, protease, hyaluronidase, helodermin, and gilatoxin. The clinical presentation of a helodermatid bite can include pain, edema, hypotension, nausea, vomiting, weakness, and diaphoresis. No antivenin is commercially available. Treatment is supportive, and although first aid measures such as suction or compression may impede venom movement, they are unproved. Cryotherapy, tourniquet, and excision are dangerous and should not be used.


Periodontal conditions following surgical and orthodontic treatment of palatally impacted maxillary canines--a follow-up study.
This follow-up study reports on the periodontal status 1 to 18 years after the completion of orthodontic treatment of unilateral palatally impacted maxillary canines and their adjacent incisors and premolars. Registrations were performed on 42 patients, 19 to 59 years old (mean 35 years) at investigation. An orthodontic pin with eyelet had been placed after exploration of the canine and, in some cases, bone removal. A flap had been raised and resutured after bone removal in 11 cases. The results showed greater mesial probing depth of the canines on the treated side, on the adjacent lateral incisors distolingually, and on the first premolars mesiolingually. Marginal bone level was found to be lower on the distal aspect of the treated canines and adjacent laterals. In general, the results showed a good gingival and periodontal status with slight differences between treated and untreated sides.


Diagnosis and surgical correction of patent ductus venosus in a calf.
Patent ductus venosus was diagnosed in a 10-week-old Holstein heifer with acute onset of collapse and marked tenesmus. Additional clinical signs observed during the course of hospitalization included depression, anorexia, hind limb ataxia, bruxism, and poor growth. Clinicopathologic test results included high blood ammonia concentration, prolonged sulfobromophthalein half-life, and high serum bile acid concentration. Liver biopsy revealed mild periportal fibrosis, but no appreciable hepatocyte atrophy. Mesenteric portography and percutaneous ultrasonography confirmed the patent ductus venosus. An atrial septal defect prosthesis was placed in the ductus venosus, using a catheterization technique. After surgery, however, clinicopathologic test results were unchanged. Ultrasonography revealed that the prosthesis had pulled away from one side of the vessel. When the calf was 10.5 months old, surgical correction was achieved by a transhepatic ligation technique. Ultrasonography confirmed closure of the ductus venosus during and after surgery. Blood ammonia and serum bile acid concentrations and sulfobromophthalein half-life were normal 3 weeks after surgery. The calf had no further episodes of hepatoencephalopathy and was successfully bred at 18 months of age.


Effect of interferon gamma on infection-related death in patients with severe injuries. A randomized, double-blind, placebo-controlled trial.
To assess the efficacy of interferon gamma in reducing infection and death in patients sustaining severe injury. Multicenter, randomized, double-blind, placebo-controlled trial with observation for 60 days and until discharge for patients with major infection on day 60. Nine university-affiliated level 1 trauma centers. Four hundred sixteen patients with severe injuries, assessed by Injury Severity Score and degree of contamination. Recombinant human interferon gamma, 100 micrograms, was administered subcutaneously once daily for 21 days (or until patient discharge if prior to 21 days) as an adjunct to standard antibiotic and supportive therapy. Incidence of major infection, death related to infection, and death. Infection rates were similar in both treatment groups; however, patients treated with interferon gamma experienced fewer deaths related to infection (seven [3%] vs 18 [9%]; P = .008) and fewer overall deaths (21 [10%] vs 30 [14%]; P = .17). While 12 early deaths (days 1 through 7) occurred in each treatment group, late death occurred in 18 placebo-treated patients and nine in interferon gamma-treated patients. The results were dominated by findings at one center, which had the highest enrollment and higher infection and death rates. Statistical analysis did not eliminate the possibility of an unidentified imbalance between arms as an explanation for the results. Further evaluation is required to determine the validity of the observed reduction in infection-related deaths in patients treated with interferon gamma.


Advances in elucidating mechanochemical complexities via implementation of a simple organic system.
Mechanochemistry is becoming increasingly popular amongst both the academic and industrial communities as an alternative method for inducing physical and chemical reactions. Despite its rapidly expanding application, little is understood of its mechanisms, greatly limiting its capacity. In the present work the application of specialty devices allowed submission of the simple organic system, α-glycine + β-malonic acid, to isolated shearing and impact treatment. In doing so, unique products were observed to result from each of these major mechanical actions; shear inducing formation of the known salt, glycinium semi-malonate (GSM), and impact yielding formation of a novel phase. Correlation of these isolated treatments with a more common ball mill indicated two unique regions within the milling jar, each characterised by varying ratios of shear and impact, leading to different products being observed. It is widely accepted that, particularly when considering organic systems, mechanical treatment often acts by inducing increases in local temperature, leading to volatilisation or melting. A combination of DSC and TGA were used to investigate the role of temperature on the system in question. Invariably, heating induced formation of GSM, with evidence supporting a eutectic melt, rather than a gas-phase reaction. Shear heating alone is unable to describe formation of the novel phase obtained through impact treatment. By considering the formation and character of mechanically produced tablets, a model is described that may account for formation of this novel phase. This system and methodology for mechanochemical study offers intriguing opportunities for continued study of this widely used and exciting field.


Immobilized enzyme cellulose hollow fibers: III. Physical properties and in vitro biocompatibility.
The initial testing of the safety of a cellulose-heparinase hollow fiber device was assessed with respect to physical properties and in vitro biocompatibility. The material cleared urea and creatinine without passing albumin, even at high flow rates. The clearance of urea and creatinine by cellulose-heparinase was equal or slightly reduced in comparision to the cellulose device. The cellulose-neparinase device tolerance to now rates was also unchanged. In addition, scanning electron microscopy of the lumen established the uniformity of the material. The analysis of clearance rates and the scanning electron micrographs show there to be no damage to the cellulose membrane after tresyl chloride activation and heparinase immobilization. The investigation of biocompatibility in an in vitro test system with whole human blood indicated that there were no significant changes in the biocompatibility of cellulose with bound heparinase. There was no change in the level of red blood cells, white blood cells, or platelets over the course of in vitro whole blood perfusion through cellulose or cellulose-heparinase hollow fiber devices. Low levels of plasma hemoglobin and complement activation were observed with cellulose and cellulose-heparinase devices. Thus, the cellulose hollow fibers can be functionalized without any changes in in vitro performance.


The maxillary sinus floor in the oral implantology.
The aim of this study was to establish the mean distances between the maxillary sinus floor and the roots of the lateral maxillary teeth in dentate subjects, respectively the mean height of the available bone for oral implant placement in the corresponding area, in edentulous ones. We determined the maxillary sinus floor position in relation to morphoclinical alveolodental benchmarks on 50 dry skulls, dentate 30 and edentulous 20, and correlations were performed by use of 40 CT-scans of the targeted area. In addition, 20 human adult cadavers were bilaterally dissected in order to bring topographical evidence at that level. The data we obtained lead us to define three dentosinusal relations: tangent (close) relation 60.8%; distanced relation 25.6%; penetrating relation: 13.6%; three subantral classes in edentulous patients, emphasizing the direct relation of the age of the edentulism and the degree of bone resorption. We discuss the results we obtained from the viewpoint of their application in the field of oral implantology. The maxillary sinus floor represents the danger zone for the oral implantology.


[Retinal ischemic changes in diabetic rats treated with pancreatic islet transplantation beneath the renal capsule].
The effect of pancreatic islet transplantation beneath the renal capsule on retinal and choroidal structure was studied using Lewis rats. Rats were divided into 3 groups: an untreated diabetic group induced by intravenous injection of streptozotocin 65 mg/kg; an islet transplanted group 1 month after induction of diabetic state; and an untreated control group. Whole retinochoroidal units were examined by light and electron-microscopy. In 6 out of 9 cases in the transplanted group, the retina showed marked destructive changes in the outer layer including pigment epithelial cells and vacuolization of the inner layer 6 months after islet transplantation. Occlusion and fibrosis of the choriocapillaris adjoining the degenerated retina were also observed. Such changes were not observed in the other groups. On electron microscopy, occlusion of capillaries and destruction of endothelial cells were frequently found in the degenerated retina. These retinal ischemic lesions appear to be caused by microvascular obstruction.


Regulatory T cells protect against hypoxia-induced pulmonary arterial hypertension in mice.
Pulmonary arterial hypertension (PAH) is a life‑threatening disease characterized by the complex proliferation of the pulmonary vascular endothelium and progressive pulmonary vascular remodeling. CD4+CD25+ regulatory T cells (Tregs) have been the focus of numerous studies into PAH. The present study aimed to investigate the role and mechanisms of Tregs in hypoxia‑induced PAH. A total of 60 male mice were divided at random into three groups: Normoxia group, hypoxia control group and Tregs group. Measurements were obtained of the right ventricle systolic pressure (RVSP) and the Fulton's index; in addition, the mRNA and protein expression of pro‑inflammatory cytokines including monocyte chemotactic protein 1 (MCP‑1), interleukin (IL)‑1β and IL‑6, as well as the anti‑inflammatory cytokine IL‑10 in the lungs were determined by reverse transcription quantitative polymerase chain reaction and western blot analysis in vivo. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured under hypoxic condition with or without Tregs for 48 h, and the proliferation rate and cell cycle of HPASMCs were determined. In addition, the protein levels of phosphorylated (p)‑Akt and p‑extracellular signal‑regulated kinase (ERK) were measured in HPASMCs in vitro. The results showed that Treg treatment significantly reduced the increased the hypoxia‑induced RVSP and Fulton's index, decreased pro‑inflammatory cytokine expression as well as enhanced IL‑10 levels in vivo. Furthermore, Treg treatment significantly reduced HPASMCs proliferation and the expression of cyclin D1, cyclin‑dependent kinase (CDK)4, p‑Akt and p‑ERK, as well as increased p27 expression in vitro. In conclusion, the results of the present study indicated that Tregs protected against hypoxia‑induced PAH in mice; the mechanisms of which may proceed via the suppression of the inflammatory response, as Tregs were found to enhance anti‑inflammatory cytokine levels, inhibit HPASMCs proliferation and regulate the cell cycle. These results therefore indicated that Tregs may be a potential novel target for the treatment of PAH.


[Protective and therapeutic effects of Shugan Lifei Recipe on rats with asthma under stress and the mechanisms].
To explore the influence of psychological factor on asthma, the protective and therapeutic effects of Shugan Lifei Recipe on rats with asthma under stress and the mechanisms. Allergy and stress-induced asthma models were established in rats by giving ovalbumin and restraining stress. Radioimmunoassay, enzyme linked immunosorbent assay, in situ hybridization and immunohistochemical method were used to detect plasma corticosterone, IL-4, IFN-gamma, expression of glucocorticoid receptor (GR) mRNA in hippocampus and adrenocorticotropic hormone corticoliberin (CRH) positive neuron in hypothalamus. Optical and electron microscopes were used to observe the morphological changes of pulmonary hilar and hippocampal tissues. Shugan Lifei Recipe (SGLFR) could reduce plasma corticosterone, decrease CRH positive neurons in paraventricular nucleus of hypothalamus, up-regulate the expression of GR mRNA in hippocampus and reduce the injury of hippocampal neuron. SGLFR had certain inhibitive effect on hyperfunction of hypothalamo-pituitary-adrenal cortex (HPA) axis in rats with asthma under stress and could also relieve the pathological changes of the pulmonary hilar tissue. The level of plasma IFN-gamma was increased while the level of plasma IL-4 was decreased in SGLFR-treated group. The mechanism of SGLFR in treating the rats with asthma under stress is probably to regulate the hyperfunction of HPA axis and the disorder of immuo-system.


Exposures and physiological responses in power tool operations: fastening vs. unfastening threaded hardware.
Powered hand tools have the potential to produce reaction forces that may be associated with upper extremity musculoskeletal disorders. This study examined and compared the kinetic and physiological impacts on operator upper extremities between the fastening and unfastening operations. Thirty-two healthy, right-handed male operators used four tools on two joint simulators at different working heights and distances in the laboratory. Three work configurations were simulated: pistol grip tools on a vertical and horizontal surface, and right angle tools on a horizontal surface. Grip force was measured on an instrumented handle attached to each tool. Muscle activity was monitored at the wrist flexor and extensor and the upper trapezius of the right arm. Paired comparisons showed that when pistol grip tools were used, the peak torque to unfasten a joint (3.7 Nm) was significantly less than to fasten the same joint (5.7 Nm). However, the exposure time was longer for unfastening cycles (98 ms more on the horizontal surface, and 107 ms more on the vertical surface). The average grip force scaled to corresponding peak tool torque revealed that the effort to react against torque was greater in unfastening cycles than in fastening cycles for all work configurations. It also showed that as a proximal stabilizer, the upper trapezius muscle had a greater activity in unfastening cycles. The kinetic and physiological responses demonstrated that unfastening fasteners, which has been neglected in the literature, have the potential to increase risk for musculoskeletal disorders and should be considered in ergonomics assessment in the workplace.


[Assessment of cardiac insufficiency].
Heart failure is a common clinical syndrome caused by different cardiovascular diseases. The prognosis is poor once the stage of congestive failure is reached. Several non-invasive and invasive techniques, described in this article, are used to objectively diagnose systolic or diastolic failure at its early stage. These investigations are needed to assess, not only the cardiac dysfunction, but also the underlying cause of the failure. Early and effective treatment should prevent or delay the occurrence of the signs of congestive failure and thus improve the prognosis.


Effects of tooth-brushing force with a desensitising dentifrice on dentine tubule patency and surface roughness.
To investigate the effects of a 5% NovaMin containing dentifrice on dentine tubule patency and surface roughness at 100g and 400g tooth brush abrasion forces. 75 polished human dentine samples were prepared and randomly allocated into one of five groups; control (1), Na2PFO3 100g abrasion force (2), NovaMin 100g (3), Na2PFO3 400g (4) and NovaMin 400g (5). The control group underwent two 2-min cycles of artificial saliva (AS), one 2-min erosion cycle; the rest underwent two toothbrush abrasion cycles in an AS/dentifrice slurry and one 2-min erosion cycle. All samples were imaged at baseline and post intervention using Tandem Scanning Microscopy and Profilometry to analyse tubule patency and roughness. Mean tubule patency increased significantly between baseline and post intervention in groups 1,2 and 4 and decreased significantly post intervention in groups 3 and 5 (p<0.01). Post intervention, there were statistically significant differences in mean patent tubules between NovaMin and the Na2PFO3 and control groups (p<0.001). Surface roughness increased for all groups between baseline and post interventions (P<0.001); mean (SD) roughness increases for groups 1, 2, 3, 4 and 5 were 0.14 (0.05) μm, 0.18 (0.04) μm, 0.16 (0.06) μm, 0.19 (0.07) μm and 0.21 (0.02) μm respectively. Differences between group 1 and 5 were significant (p<0.01). Brushing with NovaMin resulted in significant dentine tubule occlusion at 100g and 400g, but brushing with Na2PFO3 resulted in increased tubule patency. Surface roughness increased significantly at 400g brushing with NovaMin. There was no correlation between tubule patency and surface roughness. A NovaMin desensitising dentifrice resulted in tubule occlusion even at high brushing forces. There was minimal increase in surface roughness at the lower (100g) brushing force.


Controllable Self-Assembly of Amphiphilic Tadpole-Shaped Polymer Single-Chain Nanoparticles Prepared through Intrachain Photo-cross-linking.
We report the use of intramolecular cross-linking chemistry as a tool to control the self-assembly of amphiphilic diblock copolymers (di-BCPs). Two amphiphilic di-BCPs of poly( N, N'-dimethylacrylamide)- block-polystyrene (PDMA- b-PS) with photo-cross-linkable cinnamoyl groups in either hydrophobic or hydrophilic blocks were prepared using reversible addition-fragmentation chain transfer polymerization. Intramolecular photo-cross-linking of cinnamoyl groups led to the formation of tadpole-shaped polymer single-chain nanoparticles (SCNPs) consisting of a self-collapsed block as the "head" and an un-cross-linked block as the "tail". When intramolecular photo-cross-linking was carried out in hydrophobic PS blocks, a clear morphological transition from branched cylindrical micelles (for the linear di-BCP) to completely spherical micelles at a dimerization degree of ∼63% was observed. A pattern of morphological transitions from cylindrical micelles to spherical micelles is observed through stepwise downsizing the length of cylindrical micelles when increasing the self-collapse degree of PS blocks, whereas, in case of photo-cross-linking carried out in hydrophilic PDMA blocks, the size of micelles showed a dramatic increase due to the shift of hydrophobic-to-hydrophilic balance. When the cross-linking degree of PDMA blocks reached >60%, tadpole-shaped SCNPs assembled into nonconventional aggregates with a nonsmooth surface. Our results illustrate the impact of chain topologies on the self-assembly outcomes of amphiphilic di-BCPs, which likely opens a door to control the micellar morphologies from just one parent linear di-BCP, rather than resynthesizing BPCs with different volume fractions of the two blocks.


Trachoma and Ocular Chlamydial Infection in the Era of Genomics.
Trachoma is a blinding disease usually caused by infection with Chlamydia trachomatis (Ct) serovars A, B, and C in the upper tarsal conjunctiva. Individuals in endemic regions are repeatedly infected with Ct throughout childhood. A proportion of individuals experience prolonged or severe inflammatory episodes that are known to be significant risk factors for ocular scarring in later life. Continued scarring often leads to trichiasis and in-turning of the eyelashes, which causes pain and can eventually cause blindness. The mechanisms driving the chronic immunopathology in the conjunctiva, which largely progresses in the absence of detectable Ct infection in adults, are likely to be multifactorial. Socioeconomic status, education, and behavior have been identified as contributing to the risk of scarring and inflammation. We focus on the contribution of host and pathogen genetic variation, bacterial ecology of the conjunctiva, and host epigenetic imprinting including small RNA regulation by both host and pathogen in the development of ocular pathology. Each of these factors or processes contributes to pathogenic outcomes in other inflammatory diseases and we outline their potential role in trachoma.


Conservative treatment for Insertional Achilles Tendinopathy: platelet-rich plasma and focused shock waves. A retrospective study.
Insertional Achilles tendinopathy (IAT) represents a serious challenge for both physiatrists and surgeons. Here we analyse the results obtained by two conservative treatments [platelet-rich plasma (PRP) injections and focused extracorporeal shock-wave therapy (ESWT)] in physically active patients with IAT. During two consecutive periods, 45 consecutive patients with IAT were treated with 3 sessions of ESWT (2400 impulses at 0.17-0.25 mJ/mm2 per session) (24 cases between September 2011 and July 2013) or with 2 autologous PRP injections over two weeks (21 cases between September 2013 and July 2015). All patients were evaluated at 0, 2-, 4-, 6-month follow-up after therapy. The outcome measures were VISA-A, VAS, Patient Satisfaction. Intra-group analysis showed a significant improvement of VISA-A and VAS scores in both groups at all time-points. No differences between groups were observed for VAS and VISA-A scores at all time-points, excepted for VISA-A at 4-months in favour of ESWT group (P=0.049). Patient satisfaction increased progressively (>70% at 6 months) and with no differences between two groups. Both ESWT and PRP therapy are effective and safe. Our study confirms the success of these conservative treatments in Achilles tendinopathy, even in the insertional one. IIIa.


Characteristics of the redox-linked proton ejection in beef-heart cytochrome c oxidase reconstituted in liposomes.
In this paper a study is presented of the characteristics of redox-linked proton ejection exhibited by isolated beef-heart cytochrome c oxidase incorporated in asolectin vesicles. The enzyme was 90% oriented 'right-side out' as in the mitochondrial membrane. The effects on the H+/e- stoichiometry of the modalities of activation of electron flow, the pH of the medium and its ionic composition were investigated. The results obtained show that, whilst ferrocytochrome c pulses of the aerobic oxidase vesicles at neutral pH and in the presence of saturating concentrations of valinomycin and K+ to ensure charge compensation produced H+/e- ratios around 1 (as has been shown previously), oxygen pulses of reduced anaerobic vesicles supplemented with cytochrome c, gave H+/e- ratios around 0.3. The H+/e- ratios exhibited, with both reductant and oxidant pulses, a marked pH dependence. Maximum values were observed at pH 7.0-7.7, which decreased to negligible values at acidic pH with apparent pKa of 6.7-6.3. Mg2+ and Ca2+ caused a marked depression of the H+/e- ratio, which in the presence of these cations and after a few ferrocytochrome pulses, became negligible. Analysis of cytochrome c oxidation showed that the modalities of activation of electron flow and divalent cations exerted profound effects on the kinetics of cytochrome c oxidation by oxidase vesicles. The observations presented seem to provide interesting clues for the nature and mechanism of redox-linked proton ejection in reconstituted cytochrome c oxidase.


[Relationship between physical activity and health examination variables in male workers--new methods to assess physical activity and their applications to epidemiologic research].
Few epidemiological studies investigating the relationship between physical activity and cardiovascular diseases have been performed in Japan. To quantify the physical activity of individuals, a 24-hour activity record was developed to calculate 24-hour energy expenditure for use in an epidemiologic survey. Major physical activity was recorded every 15 minutes during a day and the relative metabolic rate for each physical activity was adopted from data of the Labor Science Institute in Japan. The 24-hour energy expenditure per body surface area was used as an index of physical activity. Reproducibility of this index was examined by retesting subsamples 3 months apart, and good results were confirmed. The association between physical activity and health examination variables was analyzed for the 319 male workers aged 40-49 in Osaka, Kochi, and Akita Prefecture. Twenty-four-hour energy expenditure per body surface area was positively correlated with maximal oxygen uptake and negatively correlated with skinfold thickness, resting heart rate, logarithm of triglyceride, hemoglobin and uric acid. In addition, a newly developed questionnaire on physical activity with 11 questions was administered in Osaka on 1819 male factory workers aged 40-49. From multiple regression analysis, three questions were shown to be significant predictors of 24-hour energy expenditure per body surface area--1. "What percentage of work time is spent on your feet?" 2. "When climbing three floors, which do you usually choose, the stairs or the escalator?", 3. "How long are you involved in heavy physical labor each day?" The daily physical activity score estimated using the regression equation showed good reproducibility in retesting a year apart. Controlling for age, body mass index, alcohol intake, and cigarette smoking, the score was negatively correlated to skinfold thickness, diastolic blood pressure, resting heart rate, total cholesterol, logarithm of triglyceride, hemoglobin, and uric acid; and was positively correlated to HDL-cholesterol. This cross-sectional study shows that in Japanese there is a significant relationship between physical activity and some health examination variables, and also that the survey methods to estimate physical activity can be useful for further epidemiologic studies in Japan.


CSF2RA, ANT3, and STS are autosomal in marsupials: implications for the origin of the pseudoautosomal region of mammalian sex chromosomes.
The X and Y Chromosomes (Chrs) of eutherian ("placental") mammals share a pseudo-autosomal region (PAR) that pairs and recombines at meiosis. In humans and other eutherians, the PAR contains several active genes and has also been thought to be critical for pairing and fertility. In order to explore the origin of the PAR, we cloned and mapped three human or mouse pseudoautosomal genes in marsupials, a group of mammals that diverged from eutherians about 130 (MYrBP). All three genes were autosomal in marsupials, and two co-localized with other human Xp genes on an autosome. This implies that the human PAR, like most of human Xp, represents a relic of an autosomal region added to both X and Y Chrs between 80 and 150 MYrBP.


Plasma Pyridoxal 5´-Phosphate Level in Children with Intractable and Controlled Epilepsy.
Intractable epilepsy is a serious neurologic problem with different etiologies. Decreased levels of pyridoxal phosphate in cerebral spinal fluid of patients with intractable epilepsy due to pyridoxine dependency epilepsy are reported. The aim of this study was to compare plasma pyridoxal 5´-phosphate level in patients with intractable and controlled epilepsy. This cross- sectional analytic study included 66 epileptic children, 33 patients with controlled and 33 patients with intractable epilepsy, after neonatal period up to 15 yr old of age. Thirty-three patients with intractable epilepsy (10- 162 months) and 33 patients with controlled epilepsy (14-173 months) were enrolled. The study was conducted in Pediatric Neurology Clinic of Mofid Children Hospital, Tehran, Iran from January 2010 to December 2010. Patients' clinical manifestations, laboratory and neuroimaging findings were collected. Non-fasting plasma 5´- pyridoxal phosphate levels of these subjects were assessed by high-pressure liquid chromatography. Mean plasma 5´- pyridoxal phosphate level (PLP) in patients with controlled epilepsy was 76.78±37.24 (nmol/l) (15.5-232.4). In patients with intractable epilepsy, mean plasma 5´- pyridoxal phosphate was 98.67± 80.58 (25.5- 393) nmol/l. There was no statistically significant difference between plasma pyridoxal phosphate levels of these two groups (P═0.430). Pyridoxine dependent epilepsy is under diagnosed because it is manifested by various types of seizures. Plasma pyridoxal phosphate levels did not differ in our patients with intractable or controlled epilepsy. If PDE is suspected on clinical basis, molecular investigation of ALDH7A1 mutations, as feasible test, until PDE biomarkers becomes available is recommended.


Adiposity of elderly women and its relationship with self-reported and observed physical performance.
There is a societal trend toward increasing obesity and a natural tendency for physical performance to decrease with age. Our purpose was to describe the adiposity of elderly women participating in a health screening and to determine the relationship between their adiposity and both observed and self-reported physical performance. Subjects were 104 communitydwelling elderly women (74.9+/-7.5 years). Their adiposity was described using body mass index (BMI), waist circumference, and waist to hip ratio. Physical performance was characterized using timed sit-to-stand, unilateral standing, 25-foot walk and the Physical Functioning subscale of the SF-36. Habitual activity was summarized as the number of daily hours patients estimated they spent moving about on their feet. The majority of women had excessive adiposity. Greater adiposity was associated with worse physical performance. Both Pearson correlations and multiple regression revealed BMI to be significantly predictive of all physical performance measures. Age added to the explanation of walking time and unilateral stance time. Time moving about contributed to the explanation of self-reported physical functioning. Adiposity should be documented as part of the physical therapist examination of elderly women. It may be an appropriate target of intervention if physical performance is limited.


Phosphorylation of a group of proteins related to the physiological, multihormonal regulations of the various cell types in the anterior pituitary gland.
We previously identified a group of cytoplasmic phosphoproteins whose phosphorylation could be related to the multihormonal regulation of PRL in the homogeneous tumor-derived GH cell lines (set of proteins 1-11) and in heterogeneous normal anterior pituitary cells in culture (set of proteins 1-15). In normal cells, a mixture of hypothalamic hormones induced, like the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, stronger phosphorylation changes than TRH alone. Proteins of the set 1-15 are therefore likely to be present also in the nonmammotrophic anterior pituitary cell types, where their phosphorylation can be regulated by the hormones specific of the cell type considered. This interpretation is confirmed by the presence of the same proteins in cells of the corticotroph-like AtT-20/D16 cell line and the regulation of their phosphorylation by CRF. The same phosphoproteins were also detected in non dissociated anterior pituitary tissue from ovariectomized rats. Their phosphorylation was regulated by various hormones and other extracellular agents in a way similar to their regulation in anterior pituitary cells in culture. A 5-day estradiol implant pretreatment of the ovariectomized rats, which stimulates the anterior pituitary gland both directly and indirectly, resulted in a very high level of basal phosphorylation of proteins 1-15. Only very little further stimulation was achieved by the addition of exogenous hypothalamic hormones, indicating that the actual physiological regulatory pathways are the same as those unraveled in the various cell culture model systems. In conclusion, phosphorylation of proteins 1-15 1) can be related to the multihormonal regulation of the various anterior pituitary cell types in culture and 2) corresponds to intracellular molecular mechanisms actually involved in the physiological regulations of pituitary functions in the intact anterior pituitary gland.


Is infantile autism a universal phenomenon? An open question.
What we have tried to do in this paper is to question the universality of Infantile Autism as implied by the various definitions which have been provided. Our research of the literature has convinced us that infantile autism appears to be an illness of Western Civilization, and appears in countries of high technology, where the nuclear family dominates. We indicated that no research studies were located in the U.S.A. on Hispanics, in spite of their large number. Furthermore, it was found to be quite rare among Black families. We also saw that the illness seems to be quite infrequent in Latin American countries, Africa, and India, while the rate is high in Japan, but only in westernized families. Tinbergen (1974) likewise feels that infantile autism is "actually on the increase in a number of Western and westernized societies". Two major variables which are interconnected seem to be responsible for the confusion in the findings. One of them is the problem of diagnosis. It would seem that many researchers have extended the definition of infantile autism to include other seriously afflicted children, including those who are brain-damaged. This is no surprise, since such conflicts exist as Ritvo (1981) estimating that there are 300,000 autistic children in the U.S., while a report by the National Institute for Handicapped Research estimates the number of autistic children to be 71,000 (1981). Another aspect of the findings which has been contradictory is that some investigators have found that parents of autistic children tend to be of higher S.E.S., particularly in European studies, while some studies in the U.S.A. did not find such a difference among the parents of autistic and non-autistic children. We have provided some illustrations to indicate that studies which have found no differences were not dealing exclusively with autistic children as defined by Kanner, and often used childhood schizophrenia and autism interchangeably. Cantwell, Baker, and Rutter (1978) have pointed out that this persistent difference of superior S.E.S. of parents of autistic children is an embarrassing finding which is very hard to explain if one holds that the disease is organically determined. In conclusion to his review of the literature on the universality of adult schizophrenia, Torrey (1973) wrote the following: "Studies must be done soon or it will be too late to do them at all. But, until the universal prevalence of schizophrenia becomes an open question, this task is unlikely to be undertaken". The writer of this paper is of the same opinion.(ABSTRACT TRUNCATED AT 400 WORDS)


Hidden variant of ChREBP in fat links lipogenesis to insulin sensitivity.
The ChREBP transcription factor is regulated by glucose and plays a role in insulin sensitivity, but the mechanism underlying these effects remains unclear. In a recent Nature article, Herman et al. (2012) show that a shorter ChREBP isoform (ChREBP-β) links glucose transport to lipogenesis in white adipose tissue.


Evaluation of three polygenic risk score models for the prediction of breast cancer risk in Singapore Chinese.
Genome-wide association studies (GWAS) have proven highly successful in identifying single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. The majority of these studies are on European populations, with limited SNP association data in other populations. We genotyped 51 GWAS-identified SNPs in two independent cohorts of Singaporean Chinese. Cohort 1 comprised 1294 BC cases and 885 controls and was used to determine odds ratios (ORs); Cohort 2 had 301 BC cases and 243 controls for deriving polygenic risk scores (PRS). After age-adjustment, 11 SNPs were found to be significantly associated with BC risk. Five SNPs were present in <1% of Cohort 1 and were excluded from further PRS analysis. To assess the cumulative effect of the remaining 46 SNPs on BC risk, we generated three PRS models: Model-1 included 46 SNPs; Model-2 included 11 statistically significant SNPs; and Model-3 included the SNPs in Model-2 but excluded SNPs that were in strong linkage disequilibrium with the others. Across Models-1, -2 and -3, women in the highest PRS quartile had the greatest ORs of 1.894 (95% CI = 1.157-3.100), 2.013 (95% CI = 1.227-3.302) and 1.751 (95% CI = 1.073-2.856) respectively, suggesting a direct correlation between PRS and BC risk. Given the potential of PRS in BC risk stratification, our findings suggest the need to tailor the selection of SNPs to be included in an ethnic-specific PRS model.


In situ endoscopic observation of higher-order mode conversion in a microwave mode converter based on an electro-optic probe system.
Visualizing the electromagnetic field transformation inside a microwave mode conversion region has been considered to be only realizable by simulation studies. For the first time, we present a comprehensive experimental observation of the electric field transformation occurring inside a metallic waveguide TE(01)-to-TE(02) mode converter. An efficient electro-optic (EO) probe and its associated probing system were used for measuring the electric field pattern in the external near-field region as well as in the internal and penetrated region of the mode converter. Utilizing the optically measured field patterns at the aperture of the mode converter, the conversion performance from the TE(01) mode to the TE(02) mode can be also evaluated. Experimentally measured field patterns near the apertures show excellent agreement with simulation data. The mode conversion to the next higher-order mode (TE(01) to TE(02)) was experimentally demonstrated with phase-stabilized and field-animated post processing. The presented in situ endoscopic photonic measurement technique for the field evolution inside a semi-enclosed structure could be used for visually inspecting manufacturing errors in fabricated structures, and could be of great interest for research on higher-order mode formation and transmission.


Can I get me out of my head? Exploring strategies for controlling the self-referential aspects of the mind-wandering state during reading.
Trying to focus on a piece of text and keep unrelated thoughts at bay can be a surprisingly futile experience. The current study explored the effects of different instructions on participants' capacity to control their mind-wandering and maximize reading comprehension, while reading. Participants were instructed to (a) enhance focus on what was read (external) or (b) enhance meta-awareness of mind-wandering (internal). To understand when these strategies were important, we induced a state of self-focus in half of our participants at the beginning of the experiment. Results replicated the negative association between mind-wandering and comprehension and demonstrated that both internal and external instructions impacted on the efficiency of reading following a period of induced self-focus. Techniques that foster meta-awareness improved task focus but did so at the detriment of reading comprehension, while promoting a deeper engagement while reading improved comprehension with no changes in reported mind-wandering. These data provide insight into how we can control mind-wandering and improve comprehension, and they underline that a state of self-focus is a condition under which they should be employed. Furthermore, these data support component process models that propose that the self-referent mental contents that arise during mind-wandering are distinguishable from those processes that interfere with comprehension.


Local Conformational Constraint of Firefly Luciferase Can Affect the Energy of Bioluminescence and Enzyme Stability.
Conformational dynamics contribute importantly to enzyme catalysis, such that targeted conformational constraint may affect catalysis. Firefly luciferases undergo extensive structural change during catalysis; key residues form a hydrophobic pocket, excluding water and enabling maximally energetic light production. Point mutants almost always luminesce at longer wavelengths (lower energy) than the wild type. Conformational constraint, using dipeptide analogue 3 at a position critical for optimized excited state structure, produced luciferase emission at a shorter wavelength by ~10 nm. In comparison, introduction of conformationally constrained analogues 4, 5, or 7 afforded luciferases emitting at longer wavelengths, while a related unconstrained luciferase (analogue 6) exhibited wild-type emission. The constrained luciferases tested were more stable than the wild type. Protein modeling demonstrated that the "inside" or "outside" orientation of the conformationally constrained dipeptide led to the shorter or longer emission wavelength, respectively. More broadly, these results suggest that local conformational constraint can control specific elements of enzyme behavior, both in vitro and in vivo. This represents the first example of studying enzyme function by introducing conformationally constrained dipeptides at a specific protein position. The principles discovered here in luciferase modification will enable studies to control the wavelength emission and photophysical properties of modified luciferases.


The Role of Emotion Reactivity in Health Anxiety.
Emotion reactivity, defined as heightened sensitivity, intensity, and persistence of emotional states, has been shown to contribute to the exacerbation of anxiety. However, the association between emotion reactivity and health anxiety has yet to be examined. The aim of the present investigation was to examine the unique predictive ability of emotion reactivity in terms of health anxiety in a sample of medically healthy undergraduates ( n = 194; 59.3% female, Mage = 19.42, SD = 1.51, range = 18-26 years; 84.0% Caucasian). Findings indicated that, after controlling for the effects of gender, age, and anxiety sensitivity, greater emotion reactivity significantly predicted greater overall health anxiety (3.1% variance), as well as higher levels of affective (4.1% unique variance) and behavioral (4.8% unique variance) components. Findings suggest that experiencing emotions more frequently, intensely, and for longer durations of time prior to returning to baseline are associated with greater health preoccupations.


[How to choose the ideal graft for anterior cruciate ligament reconstruction].
Indication for anterior cruciate ligament reconstruction is a debated subject and needs to be discussed on an individual basis, depending on the patient's age and physical demands. Graft selection is a crucial step for successful outcome and needs to be adapted to the patient, to the concomitant lesions, preoperative knee and lower limb injuries, but also to the surgeon's experience and preference. The present article summarizes current concepts, the pros and cons of the most used autografts and allografts, and highlights the importance to adapt postoperative rehabilitation in function of the graft.


Phytohemagglutinins augment red kidney bean (Phaseolus vulgaris L.) induced allergic manifestations.
Red kidney bean (Phaseolus vulgaris L.), a commonly consumed bean has been reported to induce allergic reactions in susceptible individuals. Phytohemagglutinins (PHAs, mainly PHA-P) contribute a major proportion of red kidney bean seeds. However, their roles in red kidney bean induced allergic reactions are still to be explored. This study was carried out to understand the role of PHAs in allergic manifestations using BALB/c mice and cultures of splenocyte, RBL-2H3 cells as well as bone marrow mast cells (BMMCs). Also, the characterization of allergic components from PHA-P was studied by LC-MS/MS. Enhanced levels of specific IgE and IgG1, clinical scores, cytokines and chemokines, β-hexosaminidase, histamine, cysteinyl leukotriene, prostaglandin D2 and abrupt histological changes in the intestine, lung and spleen indicated a pivotal role of PHA-P in red kidney bean allergy. Further, LC-MS/MS study revealed two IgE binding components of PHA-P as PHA-L and PHA-E. Enhanced specific IgE/IgG1 and β-hexosaminidase level elucidated the possible role of PHA-L and PHA-E in allergic manifestations. Furthermore, in the presence of IgE inhibitor piceatannol, reduced β-hexosaminidase release to some extent was noticed. The up regulated expression of GATA-3 and T-bet expression was observed in PHA-L as well as PHA-E groups. Taken together, this study revealed the fact that allergenicity potential of red kidney bean may get augmented due to the presence of different phytohemagglutinins. Although food allergy is an immune provocation induced mainly by dietary allergenic protein components of the food, the role of dietary lectins in the food induced allergic manifestations cannot be ruled out. Here we provide the systematic evidences about the allergenic potential of PHAs and further disclosed the culprit components as PHA-L and PHA-E. It is an important finding that the PHA-L and PHA-E can cause allergic manifestations via not only the IgE mediated pathway but also the non-IgE mediated allergic reactions as evident by the Th1/Th2 cytokines and transcription factors. Further, the PHA-L seems to be more allergenic than the PHA-E. This article is part of a Special Issue entitled: Translational plant proteomics.


Acclimatization in a hot, humid environment: body fluid adjustments.
Four trained men worked 4 h/day at 40-50% of their maximum aerobic capacity first for 3 days at 25 degrees C db, 18 degrees C wb and then for 10 consecutive days at 45 degrees C db, 32 degrees C wb. Between days 1 and 2 of heat exposure mean total circulating protein (TCP) and plasma volume (PV) increased 11.6% and 9%, respectively. Preexposure TCP and PV increased until day 6 of heat exposure. Of the protein fractions beta-globulins underwent the largest relative increase. During work movement of protein into and out of the vascular compartment was similar in control and acclimatizing subjects but the latter generally maintained a greater amount of protein and fluid within the vascular volume. There was no evidence of salt and water retention. The increase in vascualr volume was ascribed to transfer of interstitial protein and water to the vascular volume. Regression coefficients indicated significant correlations for changes in plasma volume versus heart rate, stroke volume, and cardiac output during acclimatization. It was concluded that the most critical event in heat acclimatization is the expansion of the plasma volume.


Association between family income to poverty ratio and HPV infection status among U.S. women aged 20 years and older: a study from NHANES 2003-2016.
HPV infection is closely related to the occurrence of cervical cancer and has an important adverse effect on human life and health. This study used data from the NHANES 2003-2016 to investigate the relationship between PIR and HPV infection status among Americans aged 20 and older. The data for this cross-sectional investigation came from the 2003-2016 National Health and Nutrition Examination Survey (NHANES), which included 9580 women who were 20 years of age or older. The linear and nonlinear correlations between PIR and the presence of HPV infection were investigated using multiple linear regression and smooth curve fitting. The stability of the relationship across groups was examined using subgroup analysis and interaction tests. There were 2232 impoverished homes and 2543 rich households among the 9580 adult participants aged 20 and above. PIR (ratio of income to poverty) was found to be significantly inversely related to the presence of HPV infection [0.91 (0.89, 0.94)] after adjusting for all other covariates, and the trend persisted even after categorizing PIR into high- and low-income groups (PIR>4 and PIR<1). In addition, significant negative relationships were discovered in subgroup analyses for women aged 25 to 59 [0.90 (0.88, 0.93)], non-Hispanic whites [0.80 (0.70, 0.92)], non-diabetics [0.91 (0.88, 0.94)], and those who had ever engaged in sex [0.91 (0.89, 0.94)]. PIR was highly and negatively correlated with the presence of HPV infection in American women aged 20 and older. The results of this study are of great significance for preventing HPV infection and improving the accuracy of HPV screening.


Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism.
Treatment with cinacalcet improves the control of secondary hyperparathyroidism (SHPT) and the achievement of calcium and phosphorus targets. Most data come from subjects receiving cinacalcet after several years of dialysis treatment. We therefore compared the efficacy of treatment with cinacalcet and low doses of active vitamin D to flexible doses of active vitamin D alone for the management of SHPT in patients recently initiating haemodialysis. This open-label trial randomized subjects (n = 309) with parathyroid hormone (PTH) >300 pg/mL on dialysis for 3-12 months to either cinacalcet with low-dose active vitamin D, if prescribed (cinacalcet); or usual care without cinacalcet (control). Randomized subjects were stratified by PTH at screening (300-450, >450-600, >600 pg/mL) and by the use of active vitamin D at enrolment. Treatment duration was 12 months, with primary efficacy endpoint (mean PTH reduction ≥ 30% from baseline) assessed at 6 months. The mean [standard deviation (SD)] haemodialysis vintage at enrolment was 7.2 (2.7) months; 53% of subjects were not receiving active vitamin D at enrolment. There was a significant difference in the achievement of the primary endpoint (≥ 30% PTH reduction at 6 months) between cinacalcet-treated subjects and controls in both the entire cohort (63 versus 38%; n = 304; P < 0.0001) and the subgroup of subjects not receiving active vitamin D at enrolment (70 versus 44%; n = 161; P < 0.01). Hypocalcaemia and gastrointestinal adverse events were more commonly observed in cinacalcet-treated subjects. These results indicate that cinacalcet with low-dose active vitamin D, if prescribed, provides a more effective treatment approach than usual care without cinacalcet for SHPT in incident haemodialysis patients, even in relatively treatment-naive patients.


High resource utilization in liver transplantation-how strongly differ costs between the care sectors and what are the main cost drivers?: a retrospective study.
To control treatment pathways of transplant patients across healthcare sectors, a profound knowledge of the underlying cost structure is necessary. The aim of this study was to analyze the resource utilization of patients undergoing liver transplantation. Data on resource utilization for 182 liver-transplanted patients was investigated retrospectively. The observational period started with the entry on the waiting list and ended up to 3 years after transplantation. Median treatment cost was 144 424€. During waiting time, median costs amounted to 9466€; 72% of costs were attributed to inpatient care, 3% to outpatient care, and 26% to pharmaceuticals. During the first year after transplantation, median costs of 105 566€ were calculated; 83% were allocated for inpatient and 1% outpatient care, 14% for drugs, and 1% for rehabilitative care. During follow-up after the first year of transplantation, median costs amounted to 20 115€; 75% of these were caused by pharmaceuticals, 21% by inpatient, 4% by outpatient, and <1% by rehabilitative services. Subgroup analyses (e.g., for labMELD scores) were done. Costs incurred by inpatient care and pharmaceuticals are the dominating cost factors. These findings encourage a debate on challenges and improvements for cost-efficient clinical management between different healthcare sectors.


Interferon (type-alpha and gamma) production by fresh and cryopreserved human mononuclear cells. Brief report.
A comparative study of interferon (IFN) production (type-alpha and gamma) was carried out using Ficoll-hypaque purified fresh and cryopreserved mononuclear cells from eight normal healthy individuals. Newcastle disease virus-NDV (R2B strain) was used as an inducer for type-alpha and Staphylococcal enterotoxin-A-(SEA) for type-gamma IFN production. There was no significant difference between the titres of type-alpha and gamma-IFN and lymphocyte subpopulations of fresh and cryopreserved mononuclear cells studied under identical conditions.


Purification and properties of a double-stranded ribonuclease from the yeast Saccharomyces cerevisiae.
A double-stranded ribonuclease has been purified more than 90-fold to near homogeneity from the yeast, Saccharomyces cerevisiae. The enzyme shows a high specificity for double-stranded RNA as its substrate. It has a molecular weight of 27000 as determined by sodium dodecyl sulphate/polyacrylamide gel electrophoresis. The enzyme degrades dsRNA optimally at 30 degrees C; it is stimulated by KCl and by the -SH reagent, dithiothreitol. In contrast to RNase III from Escherichia coli, the yeast enzyme is inhibited by divalent cations. Physiological studies have demonstrated that in vivo levels of the enzyme activity fell during the latter part of the exponential growth phase but rose during stationary phase. The specific activity of the enzyme in nitrogen-starved yeast cells was 2-3-fold higher than in non-starved cells. The enzyme could be detected in yeast strains containing both, one or none of the species of cytoplasmic dsRNA (L and MdsRNAs) and may, therefore, have some wider role.


Telemedicine and other care models in pediatric rheumatology: an exploratory study of parents' perceptions of barriers to care and care preferences.
The United States pediatric rheumatology workforce is committed to a mission of providing children access to pediatric rheumatology care. With a limited number and distribution of pediatric rheumatologists, telemedicine has been proposed as one way to meet this mission, yet the adoption of this modality has been slower than expected. The purpose of this study was to explore the parent perspective on barriers to accessing pediatric rheumatology care and to explore the acceptability of telemedicine and other alternative care models. Over a period of six weeks, all new and return English-speaking parents/guardians of patients visiting a single center were offered an opportunity to complete a survey which assessed barriers to care and interest in alternative models of care. Responses were analyzed using descriptive statistics. Survey response rate was 72% (159/221). Twenty-eight percent (45/159) traveled more than three hours to the pediatric rheumatology clinic, and 43% (65/152) reported travel as inconvenient. An overwhelming majority of respondents (95%, 144/152) reported a preference for in-person visits over the option of telemedicine. This preference was similar regardless of whether respondents reported travel to the clinic as inconvenient vs convenient (inconvenient 92%, 60/65; convenient 97%, 84/87; p = 0.2881) and despite those reporting travel as inconvenient also reporting greater difficulty with several barriers to care. Those familiar with telemedicine were more likely to report a preference for telemedicine over in-person visits (27%, 3/11 vs 3%, 4/140; p = 0.0087). The option of an outreach clinic was acceptable to a majority (63%, 97/154); however, adult rheumatology and shared-care options were less acceptable (22%, 35/156 and 34%, 53/156 respectively). Among survey respondents, in-person visits were preferred over the option of telemedicine, even when travel was noted to be inconvenient. Telemedicine familiarity increased its acceptability. Outreach clinics were acceptable to a majority. Ultimately, the parent perspective can shape acceptable ways to address barriers and provide accessible care.


Conserved function of the Krüppel gap gene in the blowfly Lucilia sericata, despite anterior shift of expression.
To determine whether expression patterns of segmentation genes found in Drosophila melanogaster can be scaled to pattern larger insects, we studied the expression of the Krüppel (Kr) gene in the blowfly Lucilia sericata. Compared with Drosophila Kr, L. sericata Kr showed an unexpected 10% shift of expression towards the anterior pole. Furthermore, expression domains not found in D. melanogaster were present at the blastoderm stage of L. sericata. To compare Kr activity and function, we employed RNA interference-mediated gene silencing. We found Kr phenotypes in L. sericata comparable with those observed in D. melanogaster, demonstrating that L. sericata Kr functions as a gap gene as it does in Drosophila. Our results show that, despite an anterior shift in expression, Kr function has remained conserved during the evolution of the blowflies.


Convenient method for monitoring Abeta aggregation by quartz-crystal microbalance.
We have found that a quartz-crystal microbalance is a facile and useful tool for detecting the specific aggregation of the amyloid-beta peptides responsible for Alzheimer's disease. This method greatly reduces the time and samples (corresponds to 1 Hz frequency decrease per 30 pg mass increase on a 4.9 mm(2) electrode) that are needed in the aggregation assay, and is also applicable to molecular interactions between smaller amyloid-beta fragment peptides such as the pentapeptide KLVFF.


Fourth-order curvature energy model for the stability of bicontinuous inverted cubic phases in amphiphile-water systems.
The bicontinuous inverted cubic (Q(II)) phases of amphiphiles in water have many practical applications. It is necessary to understand the stability of these phases as a function of composition and ambient conditions in order to make the best use of them. Moreover, many biomembrane lipids and some biomembrane lipid extracts form Q(II) phases. The stability of Q(II) phases in a given lipid composition is closely related to the susceptibility of that composition to membrane fusion: changes in composition that stabilize Q(II) phases usually increase the rate of membrane fusion. However, the factors determining Q(II) phase stability are not fully understood. Previously, an expression was derived for the curvature free energy of Q(II) phases with respect to that of the lamellar (L(alpha)) phase using a model for the curvature energy with terms up to fourth order in curvature as formulated by Mitov. Here this model is extended to account for the effects of water content on Q(II) phase stability. It is shown that the observed L(alpha)/Q(II) phase-transition temperature, transition enthalpy, and transition kinetics are all sensitive to water content. The same observables also become sensitive to small noncurvature energy contributions to the total free-energy difference between the Q(II) and L(alpha) phases, especially the unbinding energy in the L(alpha) phase. These predictions rationalize earlier observations of Q(II) phase formation in N-monomethylated dioleoylphosphatidylethanolamine that otherwise appear to be inconsistent. The model also provides a fundamental explanation of the hysteresis typically observed in transitions between the L(alpha) and Q(II) phases. It is an accurate model of Q(II) phase stability when the ratio of the volume fraction of the lipid in the Q(II) phase unit cell is < or = 0.5.


Red cell sodium countertransport and cotransport in normotensive and hypertensive blacks.
We have previously described elevated Lii -Nao countertransport (CT) and Na-K cotransport (CO) in red cells of Caucasian patients from Boston. In this study, we report both transport systems in black patients from Philadelphia. The maximal rate (Vmax) of CT was assayed by measuring the Nao-stimulated Li efflux from cells containing +/- 6 mmol Li/liter. The Vmax of outward cotransport was assayed by measuring the furosemide-sensitive component of Na and K efflux into Mg medium from cells containing 50 mmol/liter of both ions. The mean value of CT for 18 normotensive (NT) subjects with no family history of hypertension, (-) FHH , was 0.18 +/- 0.05 (mmol/liter cells X hour); and in 14 hypertensive (HT) patients, 0.18 +/- 0.07. The mean values of Na and K cotransport were, respectively (mmol/liter cells X hour), in 18 NT subjects with (-) FHH , 0.38 +/- 0.24 and 0.50 +/- 0.28 in 18 HT subjects, 0.25 +/- 0.17 and 0.24 +/- 0.14. We conclude that there is no difference in the Vmax for CT between the two groups of black subjects, but that the Vmax for Na-K CO was significantly reduced in the HT group. Notably, the offspring of HT patients (age 14 years, n = 17) also had a marked reduction in the Vmax of Na (0.15 +/- 0.17) K cotransport (0.19 +/- 14) in comparison with the mean value of Na (0.40 +/- 0.2) and K (0.60 +/- 0.3) cotransport measured in offspring (n = 10) of NT subjects (age 14 years).(ABSTRACT TRUNCATED AT 250 WORDS)


Increased expression of thymic stromal lymphopoietin receptor in a rat model of middle cerebral artery occlusion.
Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine expressed in the skin, gut, lungs, and thymus. TSLP triggers dendritic cell-mediated T helper 2 inflammatory responses by formation of a ternary complex consisting of a heterodimer of interleukin-7 (IL-7) receptor α chain (IL-7Rα), TSLP, and the TSLP receptor chain (TSLPR). The present study aimed to investigate the expression of this ternary complex and its interaction with signal transducer and activator of transcription 5 (STAT5) in a ischemic stroke model using middle cerebral artery occlusion. Using immunofluorescence staining, we found that TSLPR was expressed widely in neurons and gliocytes. Using immunoprecipitation analysis, we detected an increased interaction between STAT5 and the ternary complex in the cortex of stroke rats. Moreover, using western blots, we found that expressions of the ternary complex and STAT5 were markedly increased in the cortex of stroke rats compared with the control and sham rats. These results suggest that the formation of the ternary TSLPR : TSLP : IL-7Rα complex may activate STAT5 or a STAT5-related signaling pathway to mediate neuroinflammation in ischemic stroke.


T807-modified human serum albumin biomimetic nanoparticles for targeted drug delivery across the blood-brain barrier.
Novel biocompatible Human Serum Albumin (HSA) nanoparticles composed of membrane of erythrocytes (ETm)-coated and DSPE-PEG3400-T807 segments have been designed for sustained drug delivery across the blood-brain barrier (BBB). The nanoparticles have developed by induced albumin self-assembly with glutathione as reducing agent. The chemical, physical and biocompatible properties of the T807/ETm-HSA nanoparticles have been characterised by hydrogen nuclear magnetic resonance, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, transmission electron microscopy, dynamic light scattering and confocal laser scanning microscopy techniques. The unique targeting properties of the nanoparticles after fabrication with the brain-targeted ligand T807 was demonstrated by their attaching to brain cells as well as their enhanced transport ability to cross the BBB. In a further demonstration of their ability to target brain cells, in vivo living imaging revealed that T807/ETm-HSA nanoparticles accumulated in the mice brain after intravenous injection. The surface modification of ETm/HSA nanoparticles with the brain-targeted T807 demonstrated in this work represents a highly novel and effective strategy to provide efficient brain targeting and shows promise for the future in using modified ETm-coated HSA nanoparticles to penetrate the brain.


Farnesoid X receptor activates transcription of the phospholipid pump MDR3.
The human multidrug resistance gene MDR3 encodes a P-glycoprotein that belongs to the ATP-binding cassette transporter family (ABCB4). MDR3 is a critical trans-locator for phospholipids across canalicular membranes of hepatocytes, evidenced by the fact that human MDR3 deficiencies result in progressive familial intrahepatic cholestasis type III. It has been reported previously that MDR3 expression is modulated by hormones, cellular stress, and xenobiotics. Here we show that the MDR3 gene is trans-activated by the farnesoid X receptor (FXR) via a direct binding of FXR/retinoid X receptor alpha heterodimers to a highly conserved inverted repeat element (a FXR response element) at the distal promoter (-1970 to -1958). In FXR trans-activation assays, both the endogenous FXR agonist chenodeoxycholate and the synthetic agonist GW4064 activated the MDR3 promoter. Deletion or mutation of this inverted repeat element abolished FXR-mediated MDR3 promoter activation. Consistent with these data, MDR3 mRNA was significantly induced by both chenodeoxycholate and GW4064 in primary human hepatocytes in time- and dose-dependent fashions. In conclusion, we demonstrate that MDR3 expression is directly up-regulated by FXR. These results, together with the previous report that the bile salt export pump is a direct FXR target, suggest that FXR coordinately controls secretion of bile salts and phospholipids. Results of this study further support the notion that FXR is a master regulator of lipid metabolism.


PAPNET computer-aided rescreening for detection of benign and malignant glandular elements in cervicovaginal smears: a review of 61 cases.
An increasing proportion of the recent cytodiagnostic literature has focused on automation of the Pap smear screening process in hopes of finding a feasible system to aid in the reduction of the number of reported false-negative cases. In a sense, these systems can be thought of as computer-driven sensitivity enhancers for better detection of abnormalities in smeared cervicovaginal specimens. The PAPNET system (Neuromedical Systems, Inc., Suffern, NY) relies on a neural network of artificial-intelligence technology to recognize the complex cellular arrays present in Pap smears, and was originally intended to aid in the identification of morphologically abnormal cells of squamous origin. Herein, we present the results of 61 smears containing a mixture of known diagnostically important benign, dysplastic, and malignant glandular cellular abnormalities which were reviewed by the PAPNET technology. The PAPNET system detected the diagnostic glandular material in 44 of the 45 benign cases reviewed (98% detection rate). In addition, the PAPNET technology identified abnormal cellular material in 15 of the 16 studied smears from patients with malignant/dysplastic morphology (94% detection rate). These data indicate that the PAPNET neural networks are capable of detecting cells with aberrant glandular cytomorphology. In both cases missed by the PAPNET system, the number of abnormal cells per slide was very low, indicating that as with human screeners, the capabilities of this semiautomated method may be exceeded when an extreme paucity of diagnostic cellular material is present in a given slide. Further and larger reviews of glandular abnormalities by automated technologies are needed to assess these systems for their true efficacy at diminishing false-negative cases.


The successful treatment with ixekizumab in a multi-failure psoriasis patient.
We report a patient with severe psoriasis who failed to respond to phototherapy, conventional systemic treatment and four biologic agents (etanercept, ustekinumab, adalimumab and secukinumab). Combination of a higher-dose secukinumab regimen with phototherapy had no success. Remarkably, ixekizumab, an IL-17A inhibitor, provided almost complete psoriasis clearance after 24 weeks of treatment. The reason for the success of ixekizumab after the failure to respond to a biologic with same mechanism of action is still unknown. Interestingly, failure of secukinumab does not preclude future therapeutic success with a second IL-17A-inhibitor.


Structure and solubility of interleukin-2 in sodium dodecyl sulfate.
The solubility of an interleukin-2 (C125A) in an aqueous sodium dodecyl sulfate (SDS) solution was examined as a function of SDS concentration. A stock interleukin-2 solution at 1.1 or 0.31 mg/mL was mixed with one-tenth volume of a stock SDS solution at various concentrations. At intermediate SDS concentrations, the interleukin-2 showed nearly complete precipitation, while lower or higher SDS concentrations resulted in an increase in protein solubility. Circular dichroic analysis indicated that the protein remaining in the supernatant at low or high SDS concentrations has an altered conformation. Sedimentation velocity analysis of interleukin-2 in 0.1% SDS showed that about half the protein was monomeric, with the remainder as large aggregates with a broad size distribution from 20 to 100 S (M(r) approximately 10(5) - 10(7). In contrast, interleukin-2 in 0.01% SDS has a much smaller distribution of aggregates, sedimenting at ca. 2-10 S.


Histone acetylase inhibitor trichostatin A induces acetylcholinesterase expression and protects against organophosphate exposure.
The biological effects of organophosphorous (OP) chemical warfare nerve agents (CWNAs) are exerted by inhibition of acetylcholinesterase (AChE), which prevents the hydrolysis of the neurotransmitter acetylcholine, leading to hypercholinergy, seizures/status epilepticus, respiratory/cardiovascular failure, and potentially death. Current investigations show that bioscavenger therapy using purified fetal bovine AChE in rodents and non-human primates and the more recently tested human butyrylcholinesterase, is a promising treatment for protection against multiple LD(50) CWNA exposures. Potential impediments, due to the complex structure of the enzyme, purification effort, resources, and cost have necessitated alternative approaches. Therefore, we investigated the effects of transcriptional inducers to enhance the expression of AChE to achieve sufficient protection against OP poisoning. Trichostatin A (TSA), an inhibitor of histone deacetylase that de-condenses the chromatin, thereby increasing the binding of transcription factors and mRNA synthesis, was evaluated for induction of AChE expression in various neuronal cell lines. Dose-response curves showed that a concentration of 333 nM TSA was optimal in inducing AChE expression. In Neuro-2A cells, TSA at 333 nM increased the extracellular AChE activity approximately 3-4 fold and intracellular enzyme activity 10-fold. Correlating with the AChE induction, TSA pre-treatment significantly protected the cells against exposure to the organophosphate diisopropylfluorophosphate, a surrogate for the chemical warfare agents soman and sarin. These studies indicate that transcriptional inducers such as TSA up-regulate AChE, which then can bioscavenge any organophosphates present, thereby protecting the cells from OP-induced cytotoxicity. In conclusion, transcriptional inducers are prospective new methods to protect against CWNA exposure.


The mcm5-bob1 bypass of Cdc7p/Dbf4p in DNA replication depends on both Cdk1-independent and Cdk1-dependent steps in Saccharomyces cerevisiae.
The roles in DNA replication of two distinct protein kinases, Cdc7p/Dbf4p and Cdk1p/Clb (B-type cyclin), were studied. This was accomplished through a genetic and molecular analysis of the mechanism by which the mcm5-bob1 mutation bypasses the function of the Cdc7p/Dbf4p kinase. Genetic experiments revealed that loss of either Clb5p or Clb2p cyclins suppresses the mcm5-bob1 mutation and prevents bypass. These two cyclins have distinct roles in bypass and presumably in DNA replication as overexpression of one could not complement the loss of the other. Furthermore, the ectopic expression of CLB2 in G1 phase cannot substitute for CLB5 function in bypass of Cdc7p/Dbf4p by mcm5-bob1. Molecular experiments revealed that the mcm5-bob1 mutation allows for constitutive loading of Cdc45p at early origins in arrested G1 phase cells when both kinases are inactive. A model is proposed in which the Mcm5-bob1 protein assumes a unique molecular conformation without prior action by either kinase. This conformation allows for stable binding of Cdc45p to the origin. However, DNA replication still cannot occur without the combined action of Cdk1p/Clb5p and Cdk1p/Clb2p. Thus Cdc7p and Cdk1p kinases catalyze the initiation of DNA replication at several distinct steps, of which only a subset is bypassed by the mcm5-bob1 mutation.


First reported case of paratesticular seminoma in a postpubertal cryptorchid testis.
Cryptorchidism is a very common anomaly, affecting 2-4% of male infants and is more common in premature infants. The long-term outcome despite orchidopexy still remains problematic and controversial with a risk of developing cancer 5-10 times greater than normal. Paratesticular tumors are mostly benign and very rare in children however malignant paratesticular tumors do arise, the most common being rhabdomyosarcoma. Primary paratesticular seminoma is extremely rare by itself and in most cases is associated with foci of seminoma within the testis. To the best of our knowledge, our case represents the fourth reported case of paratesticular seminoma in the published literature and being the first one in cryptorchid testis.


Food protein glycation: A review focusing on stability and in vitro digestive characteristics of oil/water emulsions.
Recently, increasing studies have shown that the functional properties of proteins, including emulsifying properties, antioxidant properties, solubility, and thermal stability, can be improved through glycation reaction under controlled reaction conditions. The use of glycated proteins to stabilize hydrophobic active substances and to explore the gastrointestinal fate of the stabilized hydrophobic substances has also become the hot spot. Therefore, in this review, the effects of glycation on the structure and function of food proteins and the physical stability and oxidative stability of protein-stabilized oil/water emulsions were comprehensively summarized and discussed. Also, this review sheds lights on the in vitro digestion characteristics and edible safety of emulsion stabilized by glycated protein. It can further serve as a research basis for understanding the role of structural features in the emulsification and stabilization of glycated proteins, as well as their utilization as emulsifiers in the food industry.


A pilot Rasch scaling of lawyers' perceptions of expert bias.
How seriously do attorneys consider the biases of their retained mental health experts? Participants in this pilot study included 40 attorneys, randomly selected from a pool of members of the Pennsylvania Bar Institute, who rated-for their biasing potential-several situations that might affect the behavior of an expert. A Rasch analysis produced a linear scale as to the perceived biasing potential of these different items from most to least biasing. Among other results, the study suggests that attorneys do view mental health experts who work on both sides of cases as being more balanced in their testimony. However, they also indicated that they have a preference for using individuals who repeatedly testify for one side. Working for only one side in both civil and criminal cases yielded large scaled values. Additional comments offered by respondents indicated that: (1) an opposing expert also serving as the litigant's treater and (2) an opposing expert being viewed as a "hired gun" (supplying an opinion only for money) were viewed by subjects as not being very biased. A discussion of the results raises the need for future research in this area.


Some biological effects of calvatic acid and its analog on isolated hepatocytes.
Calvatic acid is a new antibiotic with both a carboxylic group and an azoxy function in the benzene ring. The relationship between structure and biological activity in this substance and one of its analog, phenylazoxyxyanide, was investigated. Isolated hepatocytes were used as an experimental system: the release of lactate dehydrogenase and the colchicine-binding activity of tubulin were first evaluated; effects were dose and time dependent. micromolar concentrations of these drugs determined a significant decrease of the glucose-6-phosphatase activity and a slight inhibition of aminopyrene demethylation. A toxic effect at the microsomal level and an interaction with the microtubular system are thus possible.


Characterization of two novel proteins involved in mitochondrial DNA anchoring in Trypanosoma brucei.
Trypanosoma brucei is a single celled eukaryotic parasite in the group of the Kinetoplastea. The parasite harbors a single mitochondrion with a singular mitochondrial genome that is known as the kinetoplast DNA (kDNA). The kDNA consists of a unique network of thousands of interlocked circular DNA molecules. To ensure proper inheritance of the kDNA to the daughter cells, the genome is physically linked to the basal body, the master organizer of the cell cycle in trypanosomes. The connection that spans, cytoplasm, mitochondrial membranes and the mitochondrial matrix is mediated by the Tripartite Attachment Complex (TAC). Using a combination of proteomics and RNAi we test the current model of hierarchical TAC assembly and identify TbmtHMG44 and TbKAP68 as novel candidates of a complex that connects the TAC to the kDNA. Depletion of TbmtHMG44 or TbKAP68 each leads to a strong kDNA loss but not missegregation phenotype as previously defined for TAC components. We demonstrate that the proteins rely on both the TAC and the kDNA for stable localization to the interface between these two structures. In vitro experiments suggest a direct interaction between TbmtHMG44 and TbKAP68 and that recombinant TbKAP68 is a DNA binding protein. We thus propose that TbmtHMG44 and TbKAP68 are part of a distinct complex connecting the kDNA to the TAC.


Growth and muscle development of feedlot cattle of different genetic backgrounds.
The effects of crossbreeding, cattle type and dietary energy level on semitendinosus muscle (ST) development, feedlot performance, daily carcass protein and fat gain and serum anabolic hormone concentrations were studied. Over 3 consecutive years, 176 feedlot steers representing four cattle types - unselected Hereford (UH), selected Hereford (SH), Angus x Hereford x Charolais (AHC) and Angus x Hereford x Holstein (AHH) - were fed either an all-corn silage (HS) or a high grain (HG) diet. Steers were slaughtered on day 1 and at the end of the feedlot trial, and ST muscles were removed rapidly. During years 2 and 3, single blood samples were obtained from steers on days 1, 29, 57, 113 and 169, and analyzed for insulin and growth hormone (GH). Steers fed HG had a higher (P less than .005) average daily gain (ADG) than steers fed HS, and cattle type had an effect (P less than .005) on ADG. Cattle type and HG affected (P less than .005) daily carcass protein and fat gain. Weight of ST muscle and total muscle RNA, DNA and protein content increased with frame size, and HS steers had heavier (P less than .05) ST muscles than the HG steers. Steers fed HG had higher (P less than .01) serum insulin concentrations than steers fed HS, but there were no consistent cattle type effects. Serum GH concentrations were not affected by cattle type or diet. Serum insulin concentrations, combined across diet and cattle types, were correlated (P less than .01) with ADG; however, serum GH, assessed on the same basis, was not related to ADG. Average daily protein and fat gain were positively related to serum insulin and were negatively related to serum GH.


Integrating stratified best-worst method and GIS for landslide susceptibility assessment: a case study in Erzurum province (Turkey).
Landslides are among the most destructive geological disasters that seriously damage human life and infrastructures. Landslides mainly occur in mountainous regions around the world. One of the key processes to reduce these damages is to uncover landslide-exposed areas through different data-driven methods such as Geographical Information System (GIS) and multi-criteria decision-making (MCDM). In the literature, there are many studies developed with these fundamental tools. In this study, unlike the literature, a new landslide susceptibility assessment model is proposed by integrating GIS with the stratified best-worst method (S-BWM). This model has four main dimensions and 16 sub-dimensions under topography, environment-land, location, and hydrological factors, weighted with the S-BWM. A network was created considering the different states that may arise in the importance weights of these dimensions in the future. The transition probabilities of these states were predicted and injected into the classical BWM. Then, maps were created for these dimensions and classifications for each sub-dimension according to the map characteristics. Finally, the most susceptive landslide locations were determined with GIS-based calculations. To demonstrate the model's applicability, a case study was conducted for the Erzurum region, one of Turkey's landslide-prone regions. In addition, besides the landslide map, an analysis and discussion about the spatial distribution of susceptibility classes was presented, contributing to the study's robustness. In the results of landslide susceptibility analysis, landslides are higher in the range of about 1600-2500 m. Approximately 42% (35.59 sq. km) of the study area has high landslide susceptibility, while 58% (64.41 sq. km) has medium and low landslide susceptibility.


Super-resolution for upper abdominal MRI: Acquisition and post-processing protocol optimization using brain MRI control data and expert reader validation.
Magnetic resonance (MR) cholangiopancreatography (MRCP) is an established specialist method for imaging the upper abdomen and biliary/pancreatic ducts. Due to limitations of either MR image contrast or low through-plane resolution, patients may require further evaluation with contrast-enhanced computed tomography (CT) images. However, CT fails to offer the high tissue-ductal-vessel contrast-to-noise ratio available on T2-weighted MR imaging. MR super-resolution reconstruction (SRR) frameworks have the potential to provide high-resolution visualizations from multiple low through-plane resolution single-shot T2-weighted (SST2W) images as currently used during MRCP studies. Here, we (i) optimize the source image acquisition protocols by establishing the ideal number and orientation of SST2W series for MRCP SRR generation, (ii) optimize post-processing protocols for two motion correction candidate frameworks for MRCP SRR, and (iii) perform an extensive validation of the overall potential of upper abdominal SRR, using four expert readers with subspeciality interest in hepato-pancreatico-biliary imaging. Obtained SRRs show demonstrable advantages over traditional SST2W MRCP data in terms of anatomical clarity and subjective radiologists' preference scores for a range of anatomical regions that are especially critical for the management of cancer patients. Our results underline the potential of using SRR alongside traditional MRCP data for improved clinical diagnosis.


The new politics of U.S. health policy.
Following the demise of comprehensive health care reform in 1994, some reformers are seeking comfort in the successful "incremental" strategy for enacting Medicare that emerged out of President Harry Truman's failed campaign for national health insurance in 1948-50. But despite similarities between the Truman and Clinton health security efforts, overall contexts of government and politics are much less hospitable to governmentally funded reforms today than they were after Truman's defeat. Back then, market transformations and political dynamics were both pushing toward expanded access to health services and insurance coverage. Today, by contrast, both push in the opposite direction. The private insurance market is fragmenting, federal budgetary constraints stymie new programs, and the deficit dominates debate over existing programs. Equally important, a stable pro-reform coalition like that of Truman's day has yet to emerge, while a new and fiercely conservative corps of Republicans is championing coherent programmatic alternatives based on antigovernment premises. Although passage of the Kassebaum-Kennedy health insurance reform bill in 1996 unleashed a wave of enthusiasm about incremental health care reform, formidable political, fiscal, and technical obstacles continue to stand in the way of even relatively modest incremental solutions.


Collisional Cooling of Light Ions by Cotrapped Heavy Atoms.
We experimentally demonstrate cooling of trapped ions by collisions with cotrapped, higher-mass neutral atoms. It is shown that the lighter ^{39}K^{+} ions, created by ionizing ^{39}K atoms in a magneto-optical trap (MOT), when trapped in an ion trap and subsequently allowed to cool by collisions with ultracold, heavier ^{85}Rb atoms in a MOT, exhibit a longer trap lifetime than without the localized ^{85}Rb MOT atoms. A similar cooling of trapped ^{85}Rb^{+} ions by ultracold ^{133}Cs atoms in a MOT is also demonstrated in a different experimental configuration to validate this mechanism of ion cooling by localized and centered ultracold neutral atoms. Our results suggest that the cooling of ions by localized cold atoms holds for any mass ratio, thereby enabling studies on a wider class of atom-ion systems irrespective of their masses.


Experience with cortisone and ACTH in a private clinic.
Cortisone and ACTH are valuable agents for treating a large variety of diseases. In appropriate situations they may save life. It may be possible to prevent loss of vision in eye disease or permanent damage to important viscera in generalized disease. With ready access to these agents through the pharmacist, it is important to know that cortisone and ACTH can be used in office practice provided patients are selected carefully and followed frequently and closely. Strict observation of criteria for selection of patients limited the size of the series of patients reported upon, but by the same token the incidence of complications from therapy was exceptionally small. Every physician who elects to employ these potent hormones must become familiar with their physiological effects and with the various methods of exhibiting them. Some of these effects are noted in this paper, but the experiences reviewed here provide an incomplete picture of the wide application of cortisone and ACTH.


Successful treatment of severe hepatorenal syndrome with living donor liver transplantation.
Hepatorenal syndrome is defined as renal failure caused by acute or chronic liver failure without any laboratory or histological reasons. The exact etiology of this syndrome is unknown. However, vasodilatation in the splanchnic area as a result of cirrhosis and portal hypertension, reflex systemic and splanchnic vasoconstriction are the basic pathophysiological reasons of this syndrome. The decrease of renal perfusion, decrease in glomerular filtration rate, sodium retention and deterioration of excretion of free water are the major renal problems and these remain progressive according to the stage of liver disease. The treatment of this syndrome is correction of the underlying problem. Here, we report a patient who was having hemodialysis due to renal failure as a consequence of liver cirrhosis for three months and returned back to his normal life without a need for dialysis after liver transplantation.


Towards two-photon excited endogenous fluorescence lifetime imaging microendoscopy.
In situ fluorescence lifetime imaging microscopy (FLIM) in an endoscopic configuration of the endogenous biomarker nicotinamide adenine dinucleotide (NADH) has a great potential for malignant tissue diagnosis. Moreover, two-photon nonlinear excitation provides intrinsic optical sectioning along with enhanced imaging depth. We demonstrate, for the first time to our knowledge, nonlinear endogenous FLIM in a fibered microscope with proximal detection, applied to NADH in cultured cells, as a first step to a nonlinear endomicroscope, using a double-clad microstructured fiber with convenient fiber length (> 3 m) and excitation pulse duration (≈50 fs). Fluorescence photons are collected by the fiber inner cladding and we show that its contribution to the impulse response function (IRF), which originates from its intermodal and chromatic dispersions, is small (< 600 ps) and stable for lengths up to 8 m and allows for short lifetime measurements. We use the phasor representation as a quick visualization tool adapted to the endoscopy speed requirements.


Noradrenaline-induced afterdepolarization in cat sympathetic preganglionic neurons in vitro.
Sympathetic preganglionic neurons of the intermediolateral nucleus were identified by antidromic stimulation in the slice of the T2 or T3 segment of the cat spinal cord. In normal Krebs solution, the action potential of these neurons had a shoulder on the repolarization phase and was followed by a long-lasting afterhyperpolarization (AHP). The AHP had a fast and a slow component. Superfusion of the slice with noradrenaline (NA), 10-50 microM, resulted in depression of the shoulder on the repolarization phase of the action potential, in the appearance of an afterdepolarization (ADP), which was absent in control conditions, and in depression of the slow component of the AHP. These effects were present whether the membrane potential of the sympathetic preganglionic neurons was decreased, increased, or not changed by NA. A typical ADP had time to peak of 50 ms and decay time of 200-500 ms; the amplitude was variable and large ADPs could be suprathreshold, causing repetitive firing. The amplitude and duration of the ADP increased with NA concentration. The appearance of the ADP seemed to be independent of the depressant effect of NA on the slow AHP. The ADP was associated with a decrease in neuron input resistance and was voltage dependent, being depressed in nonlinear fashion by membrane hyperpolarization. The ADP decreased in amplitude or disappeared within a range of membrane potentials from -70 to -90 mV. The ADP was reversibly suppressed by the Ca-channel blocker cobalt (2 mM), by low Ca Krebs (0.25 mM), and by iontophoretic injection of ethyleneglycol-bis(B-aminoethyl-ether)-N,N'-tetraacetic acid into the cell. Increasing Ca concentration from 2.5 to 10.0 mM had no effect. The ADP was unaffected by tetrodotoxin, at a concentration blocking the Na spike, but was suppressed in Na-free medium, even when the Ca spike was prolonged by tetraethylammonium 20 mM. Changes in external K concentration from 3.6 to 2.5 or 10.0 mM did not change the ADP. Increasing intracellular Cl concentration or decreasing extracellular Cl concentration had no effect on the ADP. It is concluded that the ADP, evoked by NA, is due to an increase in membrane conductance involving Na and Ca ions, possibly a Ca-activated Na conductance. The ADP provides a mechanism with which NA may modulate sympathetic preganglionic neuron responsiveness to excitatory synaptic inputs.


Medical education in paradise: another facet of Hawaii.
Hawaii is synonymous with paradise in the minds of many. Few know that it is also an environment where high quality medical education is thriving. This paper outlines medical education initiatives beginning with native Hawaiian healers of centuries ago, and continuing to present-day efforts to support top-notch multicultural United States medical education across the continuum of training. The undergraduate medical education program has as its core community-based problem-based learning. The community basis of training is continued in graduate medical education, with resident doctors in the various programs rotating through different clinical experiences at various hospitals and clinics. Continuing medical education is provided by nationally accredited entities, within the local context. Educational outreach activities extend into primary and secondary schools, homeless shelters, neighbouring islands, and to countries throughout the Pacific. Challenges facing the medical education community in Hawaii are similar to those faced elsewhere and include incorporating more technology to improve efficiency, strengthening the vertical integration of the training continuum, better meeting the needs of the state, and paying for it all. Readers are invited to join in addressing these challenges to further the realisation of medical education in paradise as a paradise of medical education.


Postoperative recovery of third nerve palsy due to posterior communicating aneurysms.
Postoperative recovery of third nerve palsy due to a posterior communicating artery aneurysm was correlated with pre- and intraoperative factors. The only significant factor determining recovery was the degree of preoperative deficit. The presence of subarachnoid haemorrhage, timing of surgery and aspiration of the aneurysmal sac did not influence recovery.