Acute dialysis and continuous renal replacement: the emergence of new technology involving the nephrologist in the intensive care setting.
The emergence of dialytic support for patients with reversible renal failure was one of the most significant advances in critical care medicine. Supporting a patient with a failed organ till organ recovery has not had the same success with other organ failures. Despite the indispensable nature of the support, dialysis was intermittent at best, and carried its own morbidity. The emergence of a "continuous" dialysis delivery system, originally through an arteriovenous access and later through veno-venous methodology, began to simulate the continuity of the natural kidney, and lifted much of the fluid and drug restrictions imposed by the intermittent nature of standard dialytic therapies. Components of the system were next reviewed for improvement and biocompatability. Differences in patient outcome were documented with various component comparisons, and disparate patient tolerance of delivery modality was also clearly proven. The hemodynamic stability of continuous treatment created utilization to be focused on the more unstable, the more severely compromised patient group. In this context, comparative studies with intermittent delivery methods showed improved hemodynamic stability among patients treated with continuous renal replacement therapies (CRRT), but no clear difference in patient mortality. Patient characteristics and severity scoring have recently been undertaken to better describe the population, and attempts at dialysis dosing is currently being developed for ARF dialysis recipients. Early results seem to point toward a dialysis dose effect on mortality in certain groups of ICU acute renal failure patients. However, the dialytic process is only depurative and artificial. Plastic membrane bio-incompatibility, human physiological responses to foreign material exposure, either in the circuit material itself or introduced from therapy methodology, pose practical and theoretical problems. Recent advances in the field of bio-artificial technology have allowed the development of functioning hybrid "blood processors," which function as a renal tubule and may be able to not only "clean" blood, but also allow for other cellular functions not currently possible with dead membrane technology. Combining living cells with a continuous delivery method may be the next significant step toward a fully functional renal replacement therapy.


Batch and Continuous-Flow Iron(II)-Catalyzed Synthesis of Sulfilimines and Sulfoximines using N-Mesyloxycarbamates.
The synthesis of sulfilimines and sulfoximines with N-mesyloxycarbamates in presence of catalytic iron(II) chloride hydrate is described. The use of 1-butylimidazole as a base proved instrumental in enabling a homogeneous reaction mixture compatible with continuous flow processes. The amination is applicable to a wide range of substrates, and affords the desired product in good to excellent yields within 1 to 60 minutes.


MODULEWRITER: a program for automatic generation of database interfaces.
MODULEWRITER is a PERL object relational mapping (ORM) tool that automatically generates database specific application programming interfaces (APIs) for SQL databases. The APIs consist of a package of modules providing access to each table row and column. Methods for retrieving, updating and saving entries are provided, as well as other generally useful methods (such as retrieval of the highest numbered entry in a table). MODULEWRITER provides for the inclusion of user-written code, which can be preserved across multiple runs of the MODULEWRITER program.


Embedded ring injury of the middle finger in an amphetamine abuser.
Embedded finger-ring injury is not usually encountered in clinical practice, and most patients present with psychiatric or physical/mental impairment. We report herein an 18-year-old male amphetamine abuser who presented to our emergency department (ED) for embedded finger-ring injury over his left middle finger. The embedded ring was removed in the ED under heavy sedation, and the wound healed uneventfully over 2 weeks. Thereafter, the young man received psychiatric treatment. Embedded finger-ring injury has never been reported in a drug abuser before.


[Kinetics of furfural formation as related to heating, concentration and storage of orange juices and concentrates].
According to studies on an orange concentrate diluted back with distilled water to the desired extract content, the formation of furfural follows the pattern of a consequent reaction. After the induction period, the reaction curve takes a linear course cooresponding to a reaction of a zero order. The temperature dependence of the resultant reaction constant k obeys the ARRHENIUS equation and yields the same energy of activation for all the extract contents under investigation. This is a case of specific acid catalysis, because the reaction velocity is directly proportional to the hydronium ion activity. On a semilogarithmic scale, the dependence of the k values of the extract contents of the concentrates and of the re-constituted juice can be presented for various temperatures in the form of parallels. According to the literature, the amount of the furfural produced correlates with the quality of the orange juices and concentrates. Consequently, this amount might be used as an indicator in evaluating quality deteriorations due to unsuitable manufacturing and storage on the one hand, and for the computation and optimization of the manufacturing processes and parameters on the other hand.


Characterization of colon-specific antigen-p and isolation of immunologically active tryptic peptides.
CSAp was originally detected with antisera to an unfractionated extract of GW-39 human colonic carcinoma xenografts, and was determined to be restricted to normal and neoplastic gastrointestinal tissues and certain ovarian tumors. Gel filtration chromatography of GW-39 extract on Sepharose 4B columns reveals that more than 90% of the CSAp is associated with the void volume fraction. The smaller m.w. CSAp fraction is a population of fragments heterogeneous in respect to size but immunologically identical to the void CSAp. Efforts to dissociate intact CSAp from the void fraction by treatment with solutions of high ionic strength, SDS, non-ionic detergents, and 1 M lithium bromide have not been successful. CSAp is a glycoprotein that binds to Sepharose-concanavalin A and is distinct from other known tumor-associated antigens in immunologic and physicochemical properties. The antigen shows sensitivity to high concentrations of chaotropic reagents and especially to sulfhydryl reagents, even in low concentrations, which supports earlier results indicating that the CSAp antigenic determinant is associated with the polypeptide chain rather than with a carbohydrate moiety. CSAp has been reduced in size by either sonication or partial tryptic digestion. The former produces immunologically active fragments, heterogeneous in respect to size, that resemble the smaller size CSAp, whereas the tryptic digest generates 2 distinct peptides. The major tryptic peptide is found to have an approximate molecular size of 120,000, as determined by gel filtration.


Correlated responses in growth hormone to selection for weight gain in mice.
Correlated responses in pituitary gland weight and growth hormone (GH) concentration in the serum and pituitary were studied in lines of mice selected for growth rate, and in controls. The selection criteria were weight gain between 28 and 38 days on an ad libitum feed intake (EPA line), or on intake restricted to 80% of the control mice (EPR line), and weight gain between 48 and 58 days under the above two feeding regimes (LPA and LPR lines). The control line was maintained by random breeding. In generation 13, pituitary weight and growth hormone levels were determined at 38 days in lines EPA, EPR and the control and at 58 days in lines LPA, LPR and the control. Pituitary weight, corrected for body weight gain, was smaller in the EPA line than in the control line at 38 days and was greater in the LPR line than in the control line at 58 days. There were large differences in serum GH concentrations between the selected lines and the control; the differences were statistically significant at 38 days, with the EPA and EPR lines having lower levels than the controls. ZUSAMMENFASSUNG: Veränderung von Wachstumshormonspiegel bei Selektion für Zuwachs bei Mäusen Veränderungen im Hypophysengewicht und Wachstumshormon-(GH)-Konzentrationen im Serum und in der Hypophyse wurden bei Wachstumsselektionslinien und bei Kontrollmäusen untersucht. Selektionskriterien waren Zuwachs zwischen 28 und 38 Tagen bei ad libitum Futteraufnahme (EPA Linie) oder bei Linien, wo Futteraufnahme auf 80% derjenigen der Kontrollmäuse (EPR Linie) begrenzt wurde und Zuwachs zwischen 48 und 58 Tagen unter beiden Futterweisen (LPA und LPR Linie). Die Kontrollinie wurde durch Zufallspaarung fortgepflanzt. In Generation 13 wurden Hypophysengewicht und Wachstumshormonspiegel im Alter von 38 Tagen in Linien EPA, EPR und in Kontrollen und bei 58 Tagen in Linien LPA und LPR und Kontrollen bestimmt. Hypophysengewicht, korrigiert für Zuwachs, war geringer in der LPA Linie als in der Kontrolle bei 38 Tagen Alter und größer in der LPR Linie als in der Kontrolle bei 58 Tagen. Zwischen GH Konzentrationen selektierter und Kontrollinien waren erhebliche Differenzen, die bei 38 Tagen signifikant waren, wobei EPA und EPR Linien geringere Werte als die Kontrollen aufwiesen.


Oriented attachment kinetics for ligand capped nanocrystals: coarsening of thiol-PbS nanoparticles.
In this work, the growth kinetics of thiol-capped PbS nanoparticles was studied. Two-stage growth process was observed, which was controlled first by oriented attachment (OA) mechanism and then by the hybrid Ostwald ripening (OR) and OA mechanism. Different from the NaOH-ZnS system, where OA will occur between any two multilevel nanoparticles, an OA kinetic model only considering the attachment related to original particles was fitted well with the experimental results. Analysis reveals that this model may be a universal one to describe the OA crystal growth process of nanocrystals capped with easily destroyed ligands, such as thiol-ZnS in the previous report. The OA crystal growth characteristics determined by the surface agent were discussed and compared. We propose that with stronger surface capping, the OR growth of nanocrystals is hindered, which facilitates the size controlling via OA kinetics during nanosynthesis.


Neuropsychological, olfactory, and hygiene deficits in men with negative symptom schizophrenia.
Associations between symptom subtypes, life skills, olfactory identification, and neuropsychological ability were investigated in patients with schizophrenia and related to observations of poor personal hygiene and implied functional compromise of orbitofrontal integrity. Twenty-seven men with chronic schizophrenia were assessed using the Positive and Negative Syndrome Scale for Schizophrenia and the Life Skills Profile. Performance on the University of Pennsylvania Smell Identification Test (UPSIT), the Modified Wisconsin Card Sorting Test (MWCST), delayed response/alternation, and memory tasks derived from the Wechsler Memory Scale-Revised (WMS-R) was also compared to that of an age-, sex-, and IQ-matched control group. Patient UPSIT, MWCST, and WMS-R performance was significantly impaired in comparison to controls. Poor UPSIT performance and poor self-care were significantly associated with negative symptoms. Also, UPSIT ability was associated with performance on the MWCST in both patients and controls, whereas an association with performance on the WMS-R was only found in normal subjects rather than in the patients with schizophrenia. The importance of these findings to postulated mechanisms involving prefrontal rather than mediotemporal lobe (MTL) function in schizophrenia are discussed, as is the relevance of the use of smell identification ability to subtype identification and rehabilitative strategies.


Association between childhood health, socioeconomic and school-related factors and effort-reward imbalance at work: a 25-year follow-up study.
Stress pathways can have origins in childhood, but few early predictors have been explored in relation to adult job stress. This study examined whether childhood school, health or socioeconomic factors were associated with adult job stress. Data came from the Childhood Determinants of Adult Health study that began in 1985 with children aged 7-15 years who reported effortreward imbalance (ERI) scales at ages 31-41 years. Linear regression assessed the association between childhood factors and adult ERI adjusted for age and socioeconomic position (SEP) in childhood and adulthood. There were between 999 and 1390 participants in each analysis. Lower adulthood ERI, indicating less job stress, was predicted by several school-related factors in men. For example, each higher category of learner self-concept was associated with a 19% (95% CI - 32% to 6%) reduction in adult ERI, and each unit increase in academic attainment was associated with a 15% (95% CI -28% to 3%) reduction in adult ERI. Childhood health was associated with adult ERI. For example, in women, overweight children had 14% (95% CI 5% to 22%) higher adult ERI scores compared with healthy weight children, and each unit of negative affect was associated with 2% (95% CI 1% to 4%) increase in adult ERI. Adult SEP had no effect on these associations for men but explained some of the effect in women. Childhood SEP had inconsistent associations with adult ERI. Our findings suggest that a range of childhood socioeconomic, school- and health-related factors might contribute to the development of job stress in adulthood.


Distribution of molecular size within an unfolded state ensemble using small-angle X-ray scattering and pulse field gradient NMR techniques.
The size distribution of molecules within an unfolded state of the N-terminal SH3 domain of drk (drkN SH3) has been studied by small-angle X-ray scattering (SAXS) and pulsed-field-gradient NMR (PFG-NMR) methods. An empirical model to describe this distribution in the unfolded state ensemble has been proposed based on (i) the ensemble-averaged radius of gyration and hydrodynamic radius derived from the SAXS and PFG-NMR data, respectively, and (ii) a histogram of the size distribution of structures obtained from preliminary analyses of structural parameters recorded on the unfolded state. Results show that this unfolded state, U(exch), which exists in equilibrium with the folded state, F(exch), under non-denaturing conditions, is relatively compact, with the average size of conformers within the unfolded state ensemble only 30-40% larger than the folded state structure. In addition, the model predicts a significant overlap in the size range of structures comprising the U(exch) state with those in a denatured state obtained by addition of 2 M guanidinium chloride.


Newer aspects of hepatic encephalopathy.
Recently attempts have been made to standardize terminology in the field of hepatic encephalopathy. We are now facing a new problem. Chronic hepatitis C-induced cirrhosis occurs in an older population; this may change the presentation pattern of hepatic encephalopathy in future. Ammonia has once again become prominent as the leading toxin likely to play a role in the pathogenesis of this syndrome. How ammonia interacts with other proposed mechanisms should be an area of active research. The treatment arena has seen some advances. Unfortunately, the economics of having newer treatments approved in the USA is formidable. Rifaximine, L-ornithine-L-aspartate, sodium benzoate and possibly flumazenil appear to be significant advances. More elective shunt suppression for selected patients will be seen. Liver transplantation remains the only option for truly intractable hepatic encephalopathy.


[Fecal incontinence. Personal experience in direct sphincteric repair].
Fecal incontinence is a disabling condition causing social isolation, whose real incidence is difficult to be exactly valued because patients are often reluctant to speak about it, even with their physician, or because they don't trust on surgical procedure. Aim of this study is report our experience in sphincteric reconstruction by direct sphincteric repair in patients suffering from post-traumatic fecal incontinence. Seven patients suffering from fecal incontinence due to traumatic lesions of anal sphincterial apparatus were surgically treated between 1981-2000; in the first patient cause was an injury due to impaling, in the second a previous obstetrical lesion and in the last five a previous fistulectomy. Direct sphincteric reconstruction after finding and isolation of two retracted terminals of sectioned sphincter was performed in all the patients. Sphincteric reconstruction has been always accompanied by total parenteral nutrition for about two weeks during the postoperative period. A protective colostomy was never performed. In five cases the results were excellent: patients had continence total recovery and postoperative manometry recorded basal and voluntary contraction pressures normalisation. In the two remaining cases there was only a modest improvement because of concomitant pudendal neuropathy. No operative wound infection was observed. We hope that more attention is paid to fecal incontinence either regarding instrumental semeiotics or medical or surgical therapy. In particular, direct sphincteroplasty can restore a satisfactory continence in a strong number of patients with anal sphincterial apparatus single traumatic lesions without pudendal neuropathy, relieving them from a heavily disabling condition.


Five-year comparison of wear using oxidised zirconium and cobalt-chrome femoral heads in total hip arthroplasty: a multicentre randomised controlled trial.
Oxidised zirconium (OxZi) has been developed as an alternative bearing surface for femoral heads in total hip arthroplasty (THA). This study has investigated polyethylene wear, functional outcomes and complications, comparing OxZi and cobalt-chrome (CoCr) as part of a three-arm, multicentre randomised controlled trial. Patients undergoing THA from four institutions were prospectively randomised into three groups. Group A received a CoCr femoral head and highly cross-linked polyethylene (XLPE) liner; Group B received an OxZi femoral head and XLPE liner; Group C received an OxZi femoral head and ultra-high molecular weight polyethylene (UHMWPE) liner. At five years, 368 patients had no statistically significant differences in short-form-36 (p = 0.176 mental, p = 0.756 physical), Western Ontario and McMaster Universities Osteoarthritis Index (p = 0.847), pain scores (p = 0.458) or complications. The mean rate of linear wear was 0.028 mm/year (standard deviation (SD) 0.010) for Group A, 0.023 mm/year (SD 0.010) for Group B, and 0.09 mm/year (SD 0.045) for Group C. Penetration was significantly higher in the UHMWPE liner group compared with both XLPE liner groups (p < 0.001) but no significant difference was noted between CoCr and OxZi when articulating with XLPE (p = 0.153). In this, the largest randomised study of this bearing surface, it appears that using a XLPE acetabular liner is more important in reducing THA component wear than the choice of femoral head bearing, at mid-term follow-up. There is a non-significant trend towards lower wear, coupling OxZi rather than CoCr with XLPE but long-term analysis is required to see if this observation changes with time and becomes significant.


Peak expiratory flow rate of children working in lock factories.
Peak expiratory flow rate (PEFR) of 106 children working in different units of lock factory was measured and compared with age and sex matched control group of same socio-economic status children. All the children worked for about ten hours per day. It was observed that there was a significant decrease in PEFR of children working in the different units of lock factories i.e. Hand press, Polishing, Lock fitting, Lock packing units as compared to control group (P>0.001). The reduction percentage of PEFR was maximum in children working in polishing unit (25.48%).


Micro-computed tomography based computational fluid dynamics for the determination of shear stresses in scaffolds within a perfusion bioreactor.
Perfusion bioreactors are known to exert shear stresses on cultured cells, leading to cell differentiation and enhanced extracellular matrix deposition on scaffolds. The influence of the scaffold's porous microstructure is investigated for a polycaprolactone (PCL) scaffold with a regular microarchitecture and a silk fibroin (SF) scaffold with an irregular network of interconnected pores. Their complex 3D geometries are imaged by micro-computed tomography and used in direct pore-level simulations of the entire scaffold-bioreactor system to numerically solve the governing mass and momentum conservation equations for fluid flow through porous media. The velocity field and wall shear stress distribution are determined for both scaffolds. The PCL scaffold exhibited an asymmetric distribution with peak and plateau, while the SF scaffold exhibited a homogenous distribution and conditioned the flow more efficiently than the PCL scaffold. The methodology guides the design and optimization of the scaffold geometry.


Transseptal antegrade transcatheter aortic valve replacement for patients with no other access approach - a contemporary experience.
To assess the feasibility and outcomes in patients undergoing transvenous transseptal (TS) transcatheter aortic valve replacement (TAVR). TS approach for TAVR was abandoned in favor of retrograde transfemoral, transaortic, or transapical approaches. TS TAVR may still be warranted in patients for whom no other approach is feasible. Observational consecutive case series at a single center, to evaluate technical outcomes in inoperable patients with aortic stenosis who had contraindications for other approaches and who underwent TAVR via a transvenous TS antegrade approach using the Edwards-Sapien (ES) valve. Over a 4-month period, 9 patients underwent TS TAVR with 26 mm (n = 4) and 23 mm (n = 5) ES valves. Mean age was 84.5 ± 6.6 years and Society of Thoracic Surgeons predicted risk of mortality was 7.8 ± 2.8%. Specific contraindications for other access included iliofemoral arterial diameter <7 mm in 9 (100%), porcelain aorta in 6 (66%) patients, multiple (≥2) sternotomies in 2 (22%) patients, severe pulmonary disease in 3 (33%), extreme frailty in 1 (11%), spinal stenosis with impaired ability to rehabilitate postsurgery in 1 (11%) and apical left ventricular thrombus in 1 (11%) patient. Antegrade deployment of the ES prosthetic valve was technically feasible in 8 patients. Major bleeding occurred in 4 patients, two patients suffered acute kidney injury without need for dialysis and one patient required a permanent pacemaker. The median (25th, 75th percentiles) fluoroscopy time was 49 (34, 81) minutes and contrast volume was 150 (120, 225) ml. No patient had hemodynamically significant post-TAVR aortic insufficiency nor damage to the mitral valve. At 6 months follow-up, there were no cerebrovascular events or rehospitalizations and mean NYHA Class improved from 3.4 to 1.7. The antegrade TS approach to TAVR is a technically feasible option for "no-access" patients. Prospective assessment of the safety and efficacy of this approach in the current era warrants further study.


Osteoporosis: genetic determinants and relationship with cardiovascular disease.
Osteoporosis has become one of the major public health problems, affecting about two hundred million people worldwide, including one third of all postmenopausal women. The paper presents a review of the current literature concerning the pathophysiology and the most common genetic and environmental determinants that account for the individual predisposition to age-related osteoporosis. Particular emphasis is placed on the specific linkage between the causative factors of osteoporosis and atherosclerotic cardiovascular disease.


Changes of knee joint and ankle joint orientations after high tibial osteotomy.
We sought to determine (1) whether change in the tibial plateau inclination (TPI) after high tibial osteotomy (HTO) is different from change in the knee joint line orientation (KJLO) relative to the ground; (2) whether, in varus knee OA patients before and after HTO, these radiographic measures are different from those in normal control; and (3) whether the postoperative values of the TPI and KJLO relative to the ground are associated with short term clinical outcome scores after HTO. Fifty patients who underwent HTO and 75 normal controls were assessed with four radiographic measures. We compared the measures before HTO with those after HTO and with those of the normal controls, then examined associations between the postoperative radiographic measures and clinical outcome scores 1-year after HTO. After HTO, TPI increased 9.0°, whereas KJLO relative to the ground only increased 4.1°, with a compensatory change of the ankle joint line orientation. However, the postoperative KJLO relative to the ground in the HTO group was significantly different from that of the normal controls (mean difference, 4.9°; P < 0.001). In the multiple regression analyses, the postoperative radiographic measures were not associated with outcome clinical scores 1 year after HTO. After HTO the relative KJLO changed significantly less than did the anatomical geometry of the proximal tibia. Although the KJLO after the HTO was still significantly different from that of normal knees, its value did not adversely affect clinical outcome scores 1 year after HTO.


The aggregation of alpha-synuclein is stimulated by FK506 binding proteins as shown by fluorescence correlation spectroscopy.
Aggregation of alpha-synuclein (alpha-SYN) plays a key role in Parkinson's disease (PD). We have used fluorescence correlation spectroscopy (FCS) to study alpha-SYN aggregation in vitro and discovered that this process is clearly accelerated by addition of FK506 binding proteins (FKBPs). This effect was observed both with E. coli SlyD FKBP and with human FKBP12 and was counteracted by FK506, a specific inhibitor of FKBP. The alpha-SYN aggregates formed in the presence of FKBP12 showed fibrillar morphology. The rotamase activity of FKBP apparently accelerates the folding and subsequent aggregation of alpha-SYN. Since FK506 and other non-immunosuppressive FKBP inhibitors are known to display neuroregenerative and neuroprotective properties in disease models, the observed inhibition of rotamase activity and alpha-SYN aggregation, may explain their mode of action. Our results open perspectives for the treatment of PD with immunophilin ligands that inhibit a specific member of the FKBP family.


Flap physiology and the prediction of flap viability.
Skin flaps are classified as random, axial, musculocutaneous, or fasciocutaneous according to the anatomy by which the skin receives its blood supply. The delay phenomenon allows larger and more reliable skin flaps to be transferred but requires additional surgical procedures. Efforts to mimic the delay phenomenon by pharmacologic means have, unfortunately, been disappointing. The major recent advances in flap design and reliability have come from increased knowledge of the anatomy of skin circulation, specifically musculocutaneous and fasciocutaneous circulation. In an effort to accurately predict flap survival, various monitoring techniques have been tried. These include visual inspection of fluorescein, fluorescein photography, dermofluorometry, surface temperature readings, photoplethysmography, ultrasound Doppler flowmeters, laser Dopplers, and transcutaneous PO2 monitors. Fluorescein has proved to be consistent and reliable, and the dermofluorometer has the advantage of using smaller fluorescein doses that can be frequently repeated. The other monitoring devices each have additional advantages and disadvantages.


Factor XIII-dependent generation of 5th complement component(C5)-derived monocyte chemotactic factor coinciding with plasma clotting.
Blood coagulation or plasma clotting caused generation of a monocyte chemotactic factor(s) in vitro. The chemotactic factor, of which the apparent molecular mass was 75 kDa, shared antigenicity with complement C5 and possessed the affinity to monocytes, but not to polymorphonuclear leukocytes. The generation of the chemotactic factor was hindered in the presence of a thiol enzyme inhibitor, p-chloromercuriphenyl sulfonic acid, at the concentration of 1 mmol/l, although the gelation of plasma was apparently completed. Furthermore, the generation of chemotactic factor was not observed when a plasma deficient in blood coagulation factor XIII, which is a precursor of a thiol enzyme, plasma transglutaminase, was used; and the activity normally appeared when the deficient plasma was reconstituted with purified factor XIII or with a tissue transglutaminase prior to clotting. When the human sera were injected into guinea pig skin, the serum derived from normal plasma or from the reconstituted factor XIII deficient one caused mononuclear cell infiltration, however, the serum from the deficient plasma without reconstitution infiltrated to a significantly smaller extent. These results indicated that the complement system was initiated somehow during the clotting process resulting in the generation of the C5-derived monocyte chemotactic factor in cooperation with factor XIIIa (activated factor XIII).


Changes in adipokine expression during food deprivation in the mouse and the relationship to fasting-induced insulin resistance.
We investigated the changes in insulin resistance and adipose tissue expression of the adipokines resistin, adiponectin, and leptin and the transcription factors peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and retinoid X receptor-alpha (RXR-alpha) during 48 h of food deprivation. Insulin sensitivity (SI) declined, whereas glucose effectiveness (SG) increased. Plasma adiponectin levels declined in the first 8 h and remained constant thereafter. There was no correlation between either SI or SG and adiponectin protein or mRNA levels. PPAR-gamma mRNA abundance remained constant, whereas leptin and resistin mRNAs and plasma leptin declined and RXR-alpha mRNA abundance increased in both white and brown fat. Leptin mRNA abundance was closely correlated with SI (R2 = 0.91 and 0.87 for white and brown fat, respectively). Resistin mRNA abundance correlated inversely with SG (R2 = 0.99 and 0.84 for white and brown fat, respectively). These data indicate that changes in the expression of leptin are more closely correlated with the insulin resistance of fasting than with changes in other adipokines or RXR-alpha and PPAR-gamma expression.


Randomized crossover study that used methylene blue or random 4-quadrant biopsy for the diagnosis of dysplasia in Barrett's esophagus.
Barrett's esophagus is generally accepted to be a premalignant condition. Previous studies have suggested the use of methylene blue (MB) chromoendoscopy to aid the identification of dysplasia in Barrett's esophagus surveillance programs, but a recent study has raised the concern that MB might induce oxidative damage of DNA. The aim of this study was to compare MB directed biopsies (MBDB) with our current standard, which is random 4 quadrant biopsies (RB). A randomized prospective crossover study. Single center. Patients with a diagnosis of dysplasia identified in Barrett's esophagus within a 2-year period before entering the study. Either 4 random quadrant biopsies taken every 2 cm through the length of the Barrett's esophagus or MBDB from unstained or heterogenously stained mucosa. The number of patients with a diagnosis of dysplasia by each intervention. Thirty-six percent of eligible patients declined the invitation to participate. Thirty patients completed the crossover study. The median length of Barrett's esophagus was 5 cm (interquartile range [IQR] 3-9 cm). At baseline histology, grades were as follows: 17 low-grade dysplasia (LGD), 3 high-grade dysplasia (HGD), and 10 no dysplasia. At completion, there were 10 LGD, 8 HGD, and 12 no dysplasia. Overall, dysplasia was identified in 17 of 18 patients by RB and in 9 of 18 by MBDB (McNemar test, p = 0.02). Our study showed MBDB to be significantly less sensitive in detecting dysplasia than RB in Barrett's esophagus. Hence, we discourage its use during routine surveillance of Barrett's esophagus.


18-oxocortisol: effect of dexamethasone, ACTH and sodium restriction.
The urinary excretion of 18-oxocortisol in 37 normal subjects consuming a normal sodium diet was 1.2 +/- 0.9(SD) microgram/24 h. Dexamethasone administration to 5 normal individuals suppressed the excretion of 18-oxocortisol from 1.16 +/- 0.5 micrograms/24 h to 0.6 +/- 0.2 micrograms/24 h. While they still received dexamethasone, ACTH administration raised the 18-oxo-cortisol excretion to 3.82 +/- 1.2 micrograms/24 h. Seven normal subjects were placed on a sodium restricted diet, and the urinary excretion of 18-oxocortisol rose from 1.5 +/- 1.21 micrograms/24 h to 8.54 +/- 5.08 micrograms/24 h and aldosterone from 6.6 +/- 2.0 micrograms/24 h to 39.7 +/- 14.6 micrograms/24 h. Two of the seven individuals showed minimal increases in the excretion of 18-oxocortisol, but in all cases aldosterone increased with sodium restriction. The urinary excretion of 18-oxocortisol correlated significantly with the excretion of aldosterone, 18-hydroxycortisol, cortisol, and 19-nordeoxycorticosterone. These studies indicate that 18-oxocortisol secretion is under ACTH regulation, but since sodium restriction also increases the excretion of 18-oxocortisol, the renin-angiotensin system must also participate in its regulation. However, some individuals do not increase their excretion of 18-oxocortisol with sodium restriction, although aldosterone excretion increases as expected, suggesting that additional factors participate in the regulation of 18-oxocortisol production.


The unique role of the trigeminal autonomic reflex and its modulation in primary headache disorders.
The trigeminal autonomic reflex is a physiological reflex with an important protective function which also plays a role in pathophysiological conditions, such as primary headache. It is not understood whether the autonomic symptoms in trigeminal autonomic cephalalgias and migraine are the consequence of severe trigeminal discharge or indeed directly driven by central generators as part of the pathophysiology, underlying these syndromes. Modulating this reflex, and particularly the parasympathetic reflex arc, has been shown to be effective in treating headache. Among these modulators, left noninvasive vagal nerve stimulation has been shown to bilaterally inhibit the parasympathetic output of the reflex. Furthermore, the peripheral activation of the reflex, resulting in parasympathetic discharge, is not sufficient to provoke headache attacks in cluster headache patients, suggesting a central modulation. Here, we review the anatomy and physiology of the trigeminal autonomic reflex and its involvement in primary headache. Possible candidates who have a modulating effect, including neurostimulation and pharmacological approaches, are described.


Ohio House approves two restrictive abortion bills.
A bill prohibiting the use of state funds to pay for state employees' health benefits related to "nontherapeutic abortions" passed the House on September 9 by a vote of 60-34. The measure, HB 395, defines a "nontherapeutic abortion" as a procedure performed when the life of the mother would not be endangered by carrying the pregnancy to term; the bill was amended to exempt victims of rape and incest from the funding restriction. Under HB 395, the state would pay for benefit plans that allow state employees to purchase an optional rider for abortion coverage. Also on September 9, the House passed HB 421 by a vote of 66-28. The measure amends Ohio's informed consent law for abortion by requiring a physician, but not necessarily the same physician who will perform the procedure, to meet with the patient in person and in a private setting 24 hours prior to the procedure. Just before the vote was taken, an amendment was offered and approved 68-26 which changes Ohio's parental notification law to parental consent. Both bills have been referred to the Senate for consideration.


Induced damage zone in micro-fine dental finishing of a feldspathic porcelain.
Intraoral adjustment of ceramic prostheses involving micro-finishing a feldspathic porcelain using very fine diamond burs was reported in Med Eng Phys 2008;30:856-864 with respect to finishing force, energy and surface integrity. The measured finishing forces were found to be very small. The remaining question is whether these small forces in the micro-dental finishing induced any subsurface damage to the porcelain. This paper addresses the finite element analysis (FEA) of the finishing-induced stresses and the depths of subsurface damage in micro-fine finishing. It also reports on the measurement of the subsurface damage using scanning electron microscopy (SEM). The results indicate that while finishing using fine diamond burs diminished subsurface damage, damage depths of smaller than 18 microm remained depending on the bur depth of cut and feed rate. These damages can only be minimized under very fine finishing conditions.


Screening, staffing, and emergency preparedness at worksite wellness facilities.
The purpose of this survey was to examine compliance of worksite health and fitness facilities with the American Heart Association/American College of Sports Medicine (AHA/ACSM) recommendations for cardiovascular screening, staffing, and emergency policies for health and fitness facilities. A survey was developed and sent to 529 worksite health and fitness facilities. A total of 221 surveys were returned (42% response rate). Twelve percent of facilities had no staff supervision. Among facilities with staff, 12% were not certified in basic life support, and 6% had no national professional certification. Ninety-two percent of facilities followed a health history screening policy although 13% of these facilities administered it irregularly or not at all. Of a total 187 responding facilities, 122 (65%) defined "at risk" as two or more risk factors for heart disease. Of these, 97% either required or recommended new members obtain physician clearance before participation. Four (3%) responding facilities did not require physician clearance. Twenty-five percent of facilities experienced at least one emergency that required ambulance support in the previous year. Although this was a low response rate, most responding worksite health and fitness facilities appear to be in compliance with the AHA/ACSM recommendations yet have inconsistencies in some specific practices. There appears to be a need for further consistent implementation of these recommendations into worksite settings.


[Change of phenotypic properties of escape mutants and readaptants of influenza virus A (H1N1)pdm09 under the influence of selected mutations in the molecule of hemagglutinin.]
After the emergence and spread of pandemic H1N1 viruses in 2009, antigenic epitopes recognized by neutralizing antibodies against the hemagglutinin of influenza A/Moscow/01/09(H1N1)pdm09 viruses were studied. The purpose of the study was to obtain readapted variants of the virus from a low-virulent escapemutant that has an increased affinity of the avian and the human types cellular receptors compared to the wild type and the comparative study of their antigenic and receptor specificity. Viruses were accumulated in 10-day-old chicken embryos. The MAB panel against HA of influenza virus strain A/IIV-Moscow/01/09(H1N1)sw1 was used in the form of ascites fluids from mice. Immunization of mice, HI testing, elution of viruses from chicken erythrocytes, PCR and sequencing of readapted variants were performed by standard methods. The amino acid substitution A198E acquired in the process of readaptation leads to changes in the antigenic specificity. A correlation was found between a decrease in virulence of a low-virulent escape mutant associated with the substitution D190N in the hemagglutinin molecule and an increase in the hemagglutinating titer to inhibitors in normal mouse serum. Viruses with low affinity of cellular receptor analogs and carrying amino acid substitutions have an increased ability to elute from chicken erythrocytes. The results discuss the effect of mutations in the HA molecule of the influenza A(H1N1) pdm09 virus to the change in antigen specificity; virulence for mice, adsorption-elution at cellular receptors. A comparative study of the antigenic specificity and receptor-binding activity of the escape mutants was conducted for the hemagglutinin of the influenza virus A/Moscow/01/2009 (H1N1)swl, and the readapted variants obtained for one of the escape mutants with reduced virulence for mouse. Monitoring the pleiotropic effect of mutations in the hemagglutinin H1 molecule is necessary to predict variants of the virus with pandemic potential.


Comparative kinetics of bloodmeal intake by Triatoma infestans and Rhodnius prolixus, the two principal vectors of Chagas disease.
Chagas disease vector insects Triatoma infestans and Rhodnius prolixus (fifteen stage III nymphs per 4 litre cage) were allowed to feed on anaesthetized mice for 1 h (control group), or on active non-anaesthetized mice (NAM) for 2, 4 or 8 h exposure. The bloodmeal size (weight increase) for both species was proportional to the duration of contact with NAM, due to ingestion of multiple small bloodmeals, up to 142% of control weight for T. infestans with 8 h exposure to NAM. The mean weight increase of T. infestans nymphs after 4 h contact with NAM was similar to that of the control group, whereas for R. prolixus, 8 h contact with NAM gave only 64% of the control value. For both species of insect, within 4 h of feeding, > 20% of the bloodmeal weight was lost by defaecation and diuresis. The proportions of unfed nymphs and mortality during 2 h contact with NAM were significantly higher for R. prolixus, demonstrating better exploitation of the host blood source by T. infestans, apparently because during blood-feeding the latter insect species caused less irritation to the host.


An easy access to retrieve dental implants displaced into the maxillary sinus: the bony window technique.
To present the authors' experience concerning the removal of dental implants displaced in the maxillary sinus via an intraoral approach consisting of the creation of a bony window pedicled to the maxillary sinus membrane. Thirty-six systemically healthy patients, presenting with oral implants displaced into the maxillary sinus, but with no signs of acute or chronic sinusitis, were consecutively treated between 2002 and 2012 via an intraoral approach with the bony window technique. Removal of oral implants from the maxillary sinus was achieved in all patients, and postoperative recovery was uneventful in all of them. Computed tomographies performed after surgery showed no signs of residual sinus infection in all patients and a complete ossification of the bony window margins. Twelve of the 36 treated patients were treated with a sinus grafting procedure 12-18 months after in the same areas previously treated with the bone lid technique. Seventeen implants were placed in the grafted areas 6-9 months later and, after a further waiting period needed for osseointegration, the treated patients were rehabilitated with implant-supported prostheses. The survival rate of implants was 100%, and no complications related to the sinuses and implants were recorded. Results from this study seem to demonstrate that the bony window technique is a safe and easy way to remove oral implants from the maxillary sinus under local anesthesia. The surgical access is hardly visible 6-12 months after surgery, and maxillary sinuses appeared free from residual pathology in all treated patients. Finally, this procedure allows a second-stage sinus grafting procedure via a lateral approach as in a previously untreated maxillary sinus, thus allowing an implant-supported prosthetic restoration.


ACOG Committee Opinion No. 745: Mode of Term Singleton Breech Delivery.
There is a trend in the United States to perform cesarean delivery for term singleton fetuses in a breech presentation. The number of practitioners with the skills and experience to perform vaginal breech delivery has decreased. The decision regarding the mode of delivery should consider patient wishes and the experience of the health care provider. Obstetrician-gynecologists and other obstetric care providers should offer external cephalic version as an alternative to planned cesarean for a woman who has a term singleton breech fetus, desires a planned vaginal delivery of a vertex-presenting fetus, and has no contraindications. External cephalic version should be attempted only in settings in which cesarean delivery services are readily available. Planned vaginal delivery of a term singleton breech fetus may be reasonable under hospital-specific protocol guidelines for eligibility and labor management. If a vaginal breech delivery is planned, a detailed informed consent should be documented-including risks that perinatal or neonatal mortality or short-term serious neonatal morbidity may be higher than if a cesarean delivery is planned.


Stroke volume variation and intraoperative bleeding during functional endoscopic sinus surgery.


Effects of tributyltin at concentrations below ambient levels in seawater on Caprella danilevskii (Crustacea: Amphipoda: Caprellidae).
Hatched juveniles of Caprella danilevskii (Crustacea: Amphipoda) were exposed to one of two concentrations of tributyltin (TBT) (1.1 and 10.7 ng TBTL(-1)) for 49 d at 20 degrees C. These concentrations are near or below ambient levels in seawater. In both treatments and control, the survival rate was 100% at maturation, and >85% at the end of the experiments. Females reached maturation at 20 (median) to 21.5d at instar VII, and repeated spawning 4-5 times during the experiment. The total number of juveniles per female decreased significantly from 39.5 in the control to 24.5 and 17.5 in 1.1 ng L(-1) and 10.7 ng L(-1) treatments, respectively. An earlier study reported that as the TBT concentration in seawater increased from a 0-10 ng L(-1) regime to a 10-20 ng L(-1) regime, the number of stations where Caprella spp. could be collected decreased along the coast of the Seto Inland Sea, of Japan. Thus, the present study indicates the possibility that the extremely low concentration of TBT measured in Japanese waters after 2000 lead to a reduction in reproductive success of Caprella spp.


The Role of Surface Active Agents in Ophthalmic Drug Delivery: A Comprehensive Review.
With the significant advances made in nanotechnology, research efforts focused on developing novel drug delivery platforms that can overcome the multitude of challenges encountered in ophthalmic drug delivery. Surface active agents (SAAs) have been extensively used for the formulation of many of the dosage forms targeting ocular tissues. Novel ophthalmic carriers utilizing SAAs were broadly classified into particulate, vesicular, and controlled release drug delivery systems. Depending on their physicochemical properties, SAAs can perform a variety of roles ranging from wetting agents, emulsifiers, stabilizers, charge inducers, solubilizers, antimicrobial agents, corneal permeation enhancers, and gelling agents. Nevertheless, their use is limited by their potential toxicity and possible interactions with other formulation ingredients. This review provides a comprehensive analysis of the different functional roles of SAAs in novel ophthalmic drug delivery platforms, their mechanism of action, and limitations that need to be considered during formulation to maximize their potential benefit. Understanding the mechanisms by which they perform their different roles and the possible interactions between SAAs and other formulation ingredients can help orientate the choice of formulators toward the SAA most suitable for the intended ocular application at a concentration that is both safe and effective.


Hepatic gene expression and lipid homeostasis in C57BL/6 mice exposed to hydrazine or acetylhydrazine.
Hydrazine (HD) and acetylhydrazine (AcHD) are metabolites of the antituberculosis drug isoniazid (INH) that have been implicated in INH-induced liver damage. The hepatotoxicity of AcHD and HD were compared in adult male C57Bl/6J mice by evaluating hepatic histopathology, plasma biochemistry, and hepatic gene expression. By all measures, HD had significantly greater effects than AcHD. There was no evidence of liver damage following exposure to AcHD (300 mg/kg, po). However, HD at this dose caused marked hepatic necrosis, macrovesicular degeneration, and steatosis. Lipid accumulation was initiated 2 h after HD exposure, with hepatic macrovesicular degeneration evident after 4 h, and severe necrosis by 36 h. Gene expression profiles were compared 24 h following 100 mg/kg po of HD or AcHD. HD changed the hepatic expression of more genes than AcHD, particularly lipid synthesis, transport, and metabolism genes that may be involved in steatosis. Hepatic expression of genes regulated by peroxisome proliferator activated receptors (PPAR) and sterol regulatory element binding protein (SREBP) transcription factors was increased only by HD. The hepatotoxicty and hepatic gene expression profile of HD, but not AcHD, indicate that exposure to HD initiates a process whereby the production and intracellular transport of hepatic lipids is favored over the removal of fatty acids and their metabolites.


Characteristics of lethal substances and the removal effect of molecular sulfur in the Salmonella mutagenicity test for river sediments.
The lethal action and the effect from the removal of molecular sulfur by copper treatment were investigated in the Salmonella mutagenicity test for river sediments. Survival ratios of Ames Salmonella strains for five different sediment extracts were tested, and it was found that many of the river sediments showed the lethal action on TA98 and TA100, and the lethal action was stronger in the sample from which larger amount of extracts per unit weight were obtained. It was also found that the lethal action was reduced with the addition of the metabolizer S9 mix, and TA98 was more resistant than TA100 against the lethal substances in sediment extracts. Further, removal of molecular sulfur, one of the lethal substances, by copper treatment raised survival ratios of the tester strains. On high-pressure liquid chromatographic fractionation, the lethal substances, including molecular sulfur distributed in non-polar and slightly polar fractions, and medium or high polar fractions did not reveal lethal action. Consequently, the removal procedure of molecular sulfur was proper for applying on the fraction contained non-polar and slightly polar compounds.


De novo folding of GFP fusion proteins: high efficiency in eukaryotes but not in bacteria.
Eukaryotic genomes encode a considerably higher fraction of multi-domain proteins than their prokaryotic counterparts. It has been postulated that efficient co-translational and sequential domain folding has facilitated the explosive evolution of multi-domain proteins in eukaryotes by the recombination of pre-existent domains. Here, we tested whether eukaryotes and bacteria differ generally in the folding efficiency of multi-domain proteins generated by domain recombination. To this end, we compared the folding behavior of a series of recombinant proteins comprised of green fluorescent protein (GFP) fused to four different robustly folding proteins through six different linkers upon expression in Escherichia coli and the yeast Saccharomyces cerevisiae. We found that, unlike yeast, bacteria are remarkably inefficient at folding these fusion proteins, even at comparable levels of expression. In vitro and in vivo folding experiments demonstrate that the GFP domain imposes significant constraints on de novo folding of its fusion partners in bacteria, consistent with a largely post-translational folding mechanism. This behavior may result from an interference of GFP with adjacent domains during folding due to the particular topology of the beta-barrel GFP structure. By following the accumulation of enzymatic activity, we found that the rate of appearance of correctly folded fusion protein per ribosome is indeed considerably higher in yeast than in bacteria.


Iridium-catalyzed asymmetric ring opening of azabicyclic alkenes by amines.
The enantioselective ring-opening reactions of azabicyclic alkenes with primary and secondary aromatic amine nucleophiles are reported using an iridium catalyst generated in situ from 1.5 mol % of [Ir(COD)Cl](2) and 3 mol % of (S)-BINAP. The reaction affords the corresponding trans-1,2-diamine derivatives in moderate to good yields with moderate to high enantioselectivities (up to 97% ee). The trans-configuration of the 1,2-diamino product 2g was confirmed by X-ray crystallography.


Impact of road traffic injuries on disability rates and long-term care costs in Spain.
Road traffic injuries are one of the leading causes of increasing disability-adjusted life expectancy. We analyze long-term care needs associated with motor vehicle crash-related disability in Spain and conclude that needs attributable traffic injuries are most prevalent during victims' mid-life years, they create a significant burden for both families and society as a whole given that public welfare programmes supporting these victims need to be maintained over a long time frame. High socio-economic costs of road traffic accidents (in Spain 0.04% of the GDP in 2008) are clearly indicative of the need for governments and policymakers to strengthen road accident preventive measures.


Surgical correction of cartilaginous nasal septum deformities.
Septal cartilage deviations which are usually present in deformities of the cartilaginous nasal septum are corrected by scarification on the concave side of the curvature. Histological studies indicated that this procedure was best adapted to the structure of the elastic fibres constituting the cartilaginous nasal septum. Follow-up examinations in 33 patients who having undergone surgery showed nasal breathing to be unobstructed bilaterally in all cases; in 29 patients an aesthetically satisfactory nasal shape was restored and full re-alignment of the cartilaginous nasal septum was obtained.


6q- is an early and persistent chromosomal aberration in CD3-CD4+ T-cell clones associated with the lymphocytic variant of hypereosinophilic syndrome.
The lymphocytic variant of hypereosinophilic syndrome (LV-HES) is an underrated disease defined by the monoclonal proliferation of interleukin-5 secreting T-cells. This disease is distinguished by a period of chronic lymphoproliferation without clinical transformation, which is frequently a precursor to T-cell lymphoma. In this study, LV-HES was used as a model of pre-malignancy to identify specific marker(s) predictive of the potential for malignant transformation. The karyotypic abnormalities detected in the abnormal CD3-CD4+ T cells were further characterized by fluorescent in situ hybridization. A multi-step retrospective analysis was performed on successive blood samples during a six-year follow up to correlate the evolution of cytogenetic changes with clinical progression. Expression array analysis was used to investigate the effect of these chromosomal aberrations on gene expression. A 6q deletion was detected in the two LV-HES patients during their chronic disease phase. An additional 10p deletion was found alone or in association with the 6q defect in one patient prior to the development of a CD3-CD4+ T-cell lymphoma six years after diagnosis. We show that the 6q but not the 10p deletion is both stable and persistent throughout the chronic disease, finally emerging as the predominant aberration in the lymphoma cells. Six genes mapped to the 6q-deleted region displayed altered gene expression profiles both in the chronic and malignant disease phases. Our data suggest that the 6q deletion represents an early cytogenetic marker for T-cell transformation.


[Unilateral gigantomastia of pregnancy: case-report of a giant breast hamartoma].
Breast hamartoma is a benign tumour consisting of fat, fibrous and glandular tissue. A young woman in her 19th week of pregnancy underwent exceptional surgery for a unilateral gigantomastia secondary to a rapid-growth giant hamartoma during her second pregnancy. Rigourous clinical and ultrasonographic examinations were performed followed by multiple biopsies. The decision to perform surgery was guided by the risk to skin integrity and of tumour infarct. Our report provides detailed information on gestational benign breast tumours, on the specificities of medical imaging and breast surgery in pregnant patients.


Response to anti-programmed cell death protein-1 antibodies in men treated for platinum refractory germ cell cancer relapsed after high-dose chemotherapy and stem cell transplantation.
Treatment options for patients with platinum refractory metastatic germ cell tumours (GCT) relapsing after high-dose chemotherapy and autologous stem cell transplantation are limited and survival is poor. Antibodies directed against programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are currently assessed within clinical trials. We present updated data on our experience with checkpoint inhibitors as a compassionate use off-label treatment attempt for highly-pretreated patients with GCT and provide an overview of the current literature on PD-L1 expression in this rare tumour entity. We analysed all patients with platinum refractory GCT treated with checkpoint inhibitors at our institutions between 2015 and 2017. Data were retrieved retrospectively from the patient charts. Seven patients were treated with nivolumab or pembrolizumab. Four patients received single-dose treatment and died shortly afterwards due to tumour progression; the remaining three patients received treatment for at least 6 months. No significant treatment toxicity was observed. Long-term tumour response was achieved in two of the three patients, both of them highly positive for PD-L1 staining. We consider checkpoint inhibition to be efficient in carefully selected patients with platinum refractory GCT. However, predictive markers associated with tumour response are not yet known and larger prospective clinical trials are warranted.


Taste Preferences of Horses in Relation to Their Breed and Sex.
The aim of this study was to determine the taste preferences of horses in relation to their breed and sex. Forty-eight adult purebred Arabian, Anglo-Arabian, Polish Konik, and Polish cold-blooded horses-stallions and mares in equal numbers-were examined in the study. During the experiment, five types of industrially processed feeds based on oats and natural dried products commonly regarded as horse treats (i.e., sour and sweet apples, carrots, sugar beet molasses, and barley with salt) were given to horses in buckets on three consecutive days. The behavior of the horses during the experiment was evaluated, as was the way in which they expressed their taste preferences, the sequence in which they consumed the pellets, the time they took to become interested in the pellets, and the time they took to consume each kind of pellet. The taste preferences of the horses were found to depend on their breed and sex. Pellets containing molasses were consumed more willingly by mares than stallions. Feeds with the addition of apples or carrots were the favorite treats of all tested breeds. The greatest variety in pellet taste preferences was found in purebred Arabian horses. Pellets with a distinct sweet taste or slightly salty cereals should be given to horses if other options are not available. In most cases, these two additions were chosen last by the horses in the experiment. Primitive horses had a distinct manner of expressing taste sensations. Horse behavior indicating an interest in a feed should not be taken as a proof of its tastiness. The first food chosen is not necessarily the one consumed most quickly.


Complete remission of gastric plasmacytoma following eradication of "Candidatus Helicobacter heilmannii".
This is the first case report of gastric plasmacytoma associated with "Candidatus Helicobacter heilmannii" ('H. heilmannii') infection. The patient was a 40-year-old woman with epigastric discomfort. Upper gastrointestinal endoscopy demonstrated a white granular lesion on the wall of the gastric body. Histological studies showed numerous eosinophilic globules expanding the lamina propria mucosae. Immunohistochemically, the cells with these globules stained positive for CD138, CD79a, immunoglobulin (Ig) M, and kappa light chain, but negative for CD20, IgG, IgA, and lambda light chain. A diagnosis of plasmacytoma was made. Although a Helicobacter pylori infection was not detected, the patient received H. pylori eradication treatment. Two months after H. pylori eradication treatment, an upper gastrointestinal endoscopy showed a reduction of the white granular lesion. Eighteen months after eradication treatment, endoscopy, endoscopic ultrasonography and histological studies revealed complete remission of the lesion. No relapse has been documented 30 months after the initial diagnosis of plasmacytoma. Retrospectively, analysis of biopsy specimens removed before eradication treatment demonstrated that this patient had 'H. heilmannii' infection. Therefore, H. pylori eradication therapy should be considered as a potential first-line therapy for early-stage gastric plasmacytoma with or without H. pylori infection.


Clinical tuberculosis in 2 of 3 siblings with interleukin-12 receptor beta1 deficiency.
We describe 3 siblings with interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency, a known genetic etiology of clinical disease caused by infection with poorly virulent mycobacteria, such as mycobacteria found in bacille Calmette-Guérin (BCG) vaccines and environmental nontuberculous mycobacteria (NTM). One child had disseminated tuberculosis, the second had extraintestinal salmonellosis and pulmonary tuberculosis, and the third remained asymptomatic. IL-12Rbeta1 deficiency should be considered as a diagnosis in patients with severe salmonellosis or tuberculosis, even if they do not have disease due to BCG or NTM.


Mineral homeostasis in obesity: effects of euglycemic hyperinsulinemia.
We explored the effects of insulin on mineral homeostasis in five lean and six moderately obese nondiabetic premenopausal women. Serum and urine minerals were measured before and during the steady-state phase of a euglycemic insulin clamp. Each subject participated in two insulin clamp studies on separate days at insulin infusion rates of 10 and 40 mU/m2/min. Euglycemic hyperinsulinemia was associated with (1) a significant increase in urinary calcium excretion when expressed per minute with no change in total serum calcium; (2) a decrease in urine and serum phosphate; (3) a decrease in serum potassium with no change in urine potassium; and (4) no measurable effects on urine or serum sodium. At any given insulin level, the obese individuals excreted significantly more calcium, phosphate, and potassium per minute than lean controls. While insulin administration had no effect on serum parathyroid hormone (PTH) or vitamin D levels, baseline serum 1,25(OH)2D concentration was significantly higher and serum ultrafilterable calcium was significantly lower in obese subjects than in lean controls.


Auditory skills of figure-ground and closure in air traffic controllers.
To investigate the auditory skills of closure and figure-ground and factors associated with health, communication, and attention in air traffic controllers, and compare these variables with those of other civil and military servants. Study participants were sixty adults with normal audiometric thresholds divided into two groups matched for age and gender: study group (SG), comprising 30 air traffic controllers and control group (CG), composed of 30 other military and civil servants. All participants were asked a number of questions regarding their health, communication, and attention, and underwent the Speech-in-Noise Test (SIN) to assess their closure skills and the Synthetic Sentence Identification Test - Ipsilateral Competitive Message (SSI-ICM) in monotic listening to evaluate their figure-ground abilities. Data were compared using nonparametric statistical tests and logistic regression analysis. More individuals in the SG reported fatigue and/or burnout and work-related stress and showed better performance than that of individuals in the CG for the figure-ground ability. Both groups performed similarly and satisfactorily in the other hearing tests. The odds ratio for participants belonging in the SG was 5.59 and 1.24 times regarding work-related stress and SSI-ICM (right ear), respectively. Results for the variables auditory closure, self-reported health, attention, and communication were similar in both groups. The SG presented significantly better performance in auditory figure-ground compared with that of the CG. Self-reported stress and right-ear SSI-ICM were significant predictors of individuals belonging to the SG.


The Role of Natural Killer Cells and Regulatory T Cells While Aging with Human Immunodeficiency Virus.
Combined antiretroviral therapy (cART) has increased the quality of life of people living with HIV (PLHIV). Consequently, the number of PLHIV >50 years is increasing worldwide. Patients on cART are known to remain in a proinflammatory state. The latter is linked to the development of non-AIDS-related chronic conditions. Although the number of aging PLHIV is increasing, the effect of HIV infection on the process of aging is not fully understood. Understanding the complexity of aging with HIV by investigating the effect of the latter on different components of the innate and adaptive immune systems is important to reduce the impact of these comorbid conditions and improve the quality of life of PLHIV. The role of killer immunoglobulin receptors (KIRs), expressed on the surface of natural killer (NK) cells, and their human leukocyte antigen (HLA) ligands in the clearance, susceptibility to or disease progression following HIV infection is well established. However, data on the effect of KIR-HLA interaction in aging HIV-infected population and the development of non-AIDS-related comorbid conditions are lacking. Moreover, conflicting data exist on the role of regulatory T cells (Tregs) during HIV infection. The purpose of this review is to advance the current knowledge on the role of NK cells and Tregs while aging with HIV infection.


Protein phosphatase 1 dephosphorylates Orc2.
Phosphorylation of Thr(116) and Thr(226) on Orc2, one of the six subunits of the origin recognition complex (ORC), by cyclin A/CDK2 during S phase leads to the dissociation of Orc2, Orc3, Orc4, and Orc5 subunits (Orc2-5) from human chromatin and replication origins. The phosphorylated Orc2 becomes dephosphorylated in the late M phase of the cell cycle. Here we show that protein phosphatase 1 (PP1) dephosphorylates Orc2. Dephosphorylation of Orc2 was accompanied by associating the dissociated Orc subunits with chromatin. Inhibitors of PP1 preferentially inhibited the dephosphorylation of Orc2. The overexpression of the α, β and γ PP1 isoforms decreased the amount of phosphorylated Orc2, and the depletion of these isoforms by RNA interference increased the amount of phosphorylated Orc2. These results suggest that PP1 dephosphorylates Orc2 to promote the binding of ORC to chromatin.


Novel disease-modifying therapeutics for the treatment of Alzheimer's disease.
Alzheimer's disease is the most common cause of dementia and is becoming a global health concern. Despite a well-established understanding of the molecular mechanism involved in its pathogenesis, and millions of dollars of investment in drug discovery and clinical trials, no single molecule has yet been approved for its treatment since the advent of cholinesterase inhibitors and memantine. This review examines first the optimal use of currently approved agents and then explores in detail the current Phase II and III clinical trial landscape, while spending some time on the mechanistic details. Driven by the increasing knowledge gleaned from numerous Phase III failures and improvements in early detection and biomarkers, there is renewed enthusiasm that a cure is taking shape along the visible horizon.


[Efficacy of vigabatrin associated with carbamazepine in the treatment of epilepsy. Follow up 1993-1996].
To verify tolerance and clinical efficacy of vigabatrin (VGB), a new antiepileptic drug, in an add-on therapy with carbamazepine (CBZ). From september 1993 to december 1996, 35 patients with partial complex seizures (CPC) and CPC plus secondary generalization were treated, with VGB plus CBZ, VGB dose was 1.41 +/- 0.26 (g/die +/- SD) and CBZ 2.28 +/- 0.60 (g/die +/- SD). Patients were followed-up every 4 months showing an improvement between 61.5% and 68.8% from baseline. In all patients we observed an improvement during the follow-up period. Side effects were mild and well tolerated.


Retention characteristics of porous rooted Co-Cr-Mo alloy dental implants.
The interface characteristics of porous rooted cobalt-chromium-molybdenum alloy (Co-Cr-Mo) dental implants which had been in free standing function in canine mandibles for a period of two years were investigated. The displacement of the implants and of points on the adjacent mandibular cortex were determined by mechanical testing. Bone ingrowth was quantified, and the structure of the bone-implant interface and mandibular cortex were characterized using histologic and microradiographic analyses. Displacement characteristics were correlated with determinations of the tissue structure adjacent to and growth within the implant to provide information about the biological attachment. A correlation was found between the thickness of the buccal and lingual cortical plates and implant displacements; implants having the greatest displacement response were in mandibles with the thinnest cortical plates. A relationship could not be established between the implant displacement response and the quantitative tissue structure data. Differences observed in the displacement response of the implant by mechanical testing were not observed by clinical measurements of mobility. It was concluded that implant retention mechanical behavior results from both interfacial displacement and deflection of the adjacent mandibular structures.


Global gene expression analysis of glucose overflow metabolism in Escherichia coli and reduction of aerobic acetate formation.
During aerobic growth on glucose, Escherichia coli produces acetate in the so-called overflow metabolism. DNA microarray analysis was used to determine the global gene expression patterns of chemostat cultivations of E. coli MG1655 that were characterized by different acetate formation rates during aerobic growth on glucose. A correlation analysis identified that expression of ten genes (sdhCDAB, sucB, sucC, acnB, lpdA, fumC and mdh) encoding the TCA cycle enzymes succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinyl-CoA synthetase, aconitase, fumarase and malate dehydrogenase, respectively, and of the acs-yjcH-actP operon for acetate utilization correlated negatively with acetate formation. Relieving transcriptional control of the sdhCDAB-b0725-sucABCD operon by chromosomal promoter exchange mutagenesis yielded a strain with increased specific activities of the TCA cycle enzymes succinate dehydrogenase, alpha-ketoglutarate dehydrogenase and succinyl-CoA synthetase, which are encoded by this operon. The resulting strain produced less acetate and directed more carbon towards carbon dioxide formation than the parent strain MG1655 while maintaining high growth and glucose consumption rates.


Regulation of lutenizing hormone secretion and subunit messenger ribonucleic acid expression by gonadal steroids in perifused pituitary cells from male monkeys and rats.
The mechanisms by which gonadal steroids regulate gonadotropin secretion remain incompletely understood. As previous studies suggest that the pituitary actions of testosterone (T) and estradiol (E) differ in male primates and rodents, we compared the effects of 10 nM T, 0.1 nM E, and 10 nM dihydrotestosterone (DHT) on the LH response to hourly pulses of GnRH as well as the GnRH receptor (GnRH-R) and LH subunit messenger RNA (mRNA) levels in dispersed pituitary cells from intact male monkeys and rats. T suppressed (P < 0.01) and E increased (P < 0.05) GnRH-stimulated LH secretion by rat pituitary cells. With monkey pituitary cells, on the other hand, there was no significant effect of either T or DHT on GnRH-stimulated LH secretion. In E-treated monkey cells, a period of initial enhancement (P < 0.05) was followed by significant suppression (P < 0.05) of LH secretion. GnRH-R mRNA was unchanged by T or E in either rat or monkey cells. T suppressed LHbeta (P < 0.01) and alpha-subunit (P < 0.01) mRNAs, whereas E increased alpha-subunit (P < 0.01), but did not alter LHbeta mRNA levels in rat cells. In monkey cells, however, neither T nor E affected LHbeta or alpha-subunit mRNA levels significantly. Our results identify different regulatory mechanisms by which testicular steroid hormones control LH secretion by the pituitary in male primates and rodents. We propose that the primary site of androgen negative feedback in the male primate is to restrain GnRH pulsatile secretion, whereas in the male rat T also decreases gonadotropin synthesis and secretion by directly affecting the pituitary. E suppresses GnRH-stimulated LH secretion in the primate pituitary, but amplifies the action of GnRH in the rat. Our data also reveal that the action of T to suppress LH secretion and subunit mRNA in male rats is not through decreased GnRH-R gene expression.


An evidence-based review of systemic treatments for itch.
Many treatment modalities are used for itch treatment in daily medical practices without adequate evidence of their efficacy. The purpose of this study was to provide an evidence-based review of the literature as to the clinical benefits of systemic anti-itch treatments. We performed a systematic review and, when appropriate, meta-analysis from available placebo-controlled randomized controlled trails (RCTs). A systematic search of the literature was performed using Pub Med, Cochrane Library and EMBASE. The primary outcome was the change in the itch score comparing the intervention group and placebo group. The meta-analysis method was used to calculate the pooled outcome of each treatment modality. Twenty-six eligible RCTs were included. We found evidence for the effectiveness of: naltrexone (in cholestatic itch and atopic eczema), nalfurafine (in uraemic itch), gabapentin (in uraemic itch) and ursodeoxycholic acid (in intrahepatic cholestasis of pregnancy). The results of two RCTs with naltrexone in uremic itch are conflicting. On the other hand, we did not find any benefit from ondansetron (in cholestatic and uraemic itch), ergocalciferol (in uraemic itch), colesevelam (in cholestatic itch) or gabapentin (in cholestatic itch). The possible effectiveness of sertraline, paroxetine, cromolyn sodium, zinc sulphate, omega-3 fatty acid, montelukast, doxepin and rifampin need to be confirmed from future large studies, because the available evidence is insufficient. The findings from this study suggest the effective therapeutic approaches for itch. The major limitations are that there are small numbers of available RCTs and methodological differences across studies.


The Principles and Practice of Re-irradiation in Clinical Oncology: An Overview.
Long-term cancer survivors are at risk of the development of recurrence or a new primary cancer that requires a second (or third) radio-oncological treatment. Publications on re-irradiation have been followed and are summarised in this overview. Information from clinical and experimental animal studies suggests that specific normal tissues can tolerate a considerable retreatment radiation dose. However, the risk of normal tissue damage and the impact on the quality of life must be considered. If a second course of radiotherapy needs to be administered, this should be done with maximum care and accuracy. Optimum conformation of the dose to the planning target volume is required. For radiobiological reasons - in order to reduce the risk of late effects - hyperfractionation protocols should be applied for curative treatments. Alternatively, small volume exposure may be considered in a highly conformal, image-guided stereotactic approach.


The application of a modified neuroprosthetic hand system in a child with a C7 spinal cord injury. Case report.
A neuroprosthetic hand system developed at Case Western Reserve University has been modified for use by an 8 year old child with an incomplete C7 spinal cord injury. This system has been adapted to accommodate voluntary thumb and finger extension, and provides stimulated finger flexion and thumb position for lateral and palmar prehension. Three months were required to develop grasp with sufficient strength and coordination for functional use. This period consisted of: implantation and immobilization of percutaneous intramuscular electrodes; stimulated exercise of the muscles of the hand and forearm; programming grasp patterns; and system training. Functional assessments show that the neuroprosthetic hand system allows the subject to perform unilateral and bilateral tasks that were otherwise impossible or were previously performed bimanually. The ability to perform activities of daily living with one hand frees the contralateral upper extremity to be used either for balance which increases the work area, or to stabilize an object allowing manipulation with the instrumented hand. Telephone interviews suggest that the hand system is used on a consistent basis at home and school. This single subject application indicates that a stimulation system designed for adults with C5-6 spinal cord injuries can enhance hand function and facilitate independence in a child with a low level cervical lesion.


Association of virulence of Neisseria meningitidis with transparent colony type and low-molecular-weight outer membrane proteins.
To assess the factors that might be associated with the virulence of Neisseria meningitidis, isolates from the blood or cerebrospinal fluid of patients with meningococcal disease and meningococcal isolates from the nasopharynx of asymptomatic carriers were compared with regard to opacity or transparency of colonies. Neisseria meningitidis isolated from patients with meningitis and septicemia grew in predominantly transparent colonies, whereas meningococci isolated from asymptomatic carriers generally formed opaque or a mixture of opaque and transparent colonies. Piliated meningococci from opaque colonies attached to human mucosal cells in significantly greater numbers than did piliated meningococci from transparent colonies of the same isolate. Meningococci from transparent colonies were more resistant to killing by normal human serum than were meningococci from isogenic opaque colonies. Disease-associated isolates that formed transparent colonies contained one or more heat-modifiable outer membrane proteins of molecular weight 26,000-32,000 which were not found in some isogenic clones that formed opaque colonies. Transparency of meningococcal colonies may be an important marker for factors that mediate meningococcal virulence.


Children's cycling skills: Development of a test and determination of individual and environmental correlates.
Children's ability to perform cycling skills was found to play an important role in cycling accidents. Therefore, this study developed a test to gain a detailed insight into the cycling skills of 9-10 year old children and evaluated individual and physical environmental correlates of cycling skills. Children (n=93) took a cycling test consisting of 13 test stations. In addition, parents completed a questionnaire on school commuting behavior. An exploratory factor analysis was conducted to investigate the factor structure of the cycling test and ICC's were calculated to examine interrater reliability. Descriptive statistics were executed on children's cycling skill scores. Regression analyses were conducted to evaluate individual and environmental correlates of cycling skills. Three factors were extracted: the 'during-cycling skills', the 'before/after-cycling skills' and a 'transitional-cycling skills' factor. These factors accounted for 56.74% of the total variance. Furthermore, intraclass correlation coefficients ranged from 0.75 to 0.98. For all cycling skill, except two, 50% of children scored higher than 7.5/10. Additionally, 18.4% of children scored lower than 3/10 on at least two cycling skills. Parental perceived motor competence of the child explained 10% of the variance in cycling skills (β=0.33), residential density explained 12% of the variance (β=-0.37). In order to get an overall picture of the cycling skills of children, the 'during-cycling skills', the 'before/after-cycling skills' and the 'transitional-cycling skills' need to be examined. Furthermore, Flemish children of the 4th grade scored well on cycling skills. However, cycle training programs should focus more on one-handed skills and those children scoring lower than 3/10 on one or more cycling skills.


Dosing frequency of unfractionated heparin thromboprophylaxis: a meta-analysis.
In medical patients, it is unclear whether thromboprophylaxis with low-dose unfractionated heparin (UFH) should be administered bid or tid. This study was a mixed-treatment comparison meta-analysis of randomized control trials that enrolled hospitalized nonsurgical patients at risk for VTE and compared UFH bid, UFH tid, or low-molecular-weight heparin (LMWH) to one another or to an inactive control subject. DVT, pulmonary embolism (PE), major bleeding, and death were measured. A Bayesian framework using a random-effects model was applied. Sixteen trials with moderate methodologic quality enrolling 27,667 patients contributed to this analysis. The relative risk and 95% credible intervals comparing UFH tid to UFH bid for DVT, PE, death, and major bleeding were 1.56 (0.64-4.33), 1.67 (0.49-208.09), 1.17 (0.72-1.95), and 0.89 (0.08-7.05), respectively. When compared with either dose of UFH, the use of LMWH has an effect similar to UFH on all four outcomes. Moderate-quality evidence suggests that subcutaneous UFH bid and UFH tid do not differ in effect on DVT, PE, major bleeding, and mortality. Either of the two dosing regimens of UFH or LMWH appears to be a reasonable strategy for thromboprophylaxis in medical patients. A future randomized trial comparing the two doses of UFH is very unlikely, considering the very large sample size that would be required to demonstrate a significant difference, which, if it exists, is undoubtedly small.


Chronic nicotine in utero selectively suppresses hypoxic sensitivity in neonatal rat adrenal chromaffin cells.
Nicotine in cigarette smoke has been linked to several deleterious side effects on the offspring of smoking mothers, including impaired development of the sympathoadrenal system, abnormal arousal reflexes, and sudden infant death syndrome. Catecholamine (CA) release from adrenomedullary chromaffin cells (AMCs) in response to asphyxial stressors, e.g., low O(2) (hypoxia) and elevated CO(2) (hypercapnia), is critical for adaptation to extrauterine life and occurs before splanchnic innervation. Here, we investigated the effects of prenatal nicotine bitartrate exposure on the ability of neonatal (P0) rat AMCs to respond appropriately to asphyxial stressors. Control AMCs isolated from pups born to saline-treated dams displayed typical responses to hypoxia and hypercapnia, including inhibition of outward K(+) current, membrane depolarization, increased cytosolic calcium, and CA secretion. In contrast, P0 AMCs from pups born to nicotine-treated dams showed a marked suppression or loss of hypoxic sensitivity, although hypercapnic sensitivity and the expression of CO(2) markers (i.e., carbonic anhydrase I and II) appeared normal. Moreover, isolated saline-treated P0 AMCs lost their hypoxic sensitivity when grown in culture for approximately 1 wk in the presence of a subsaturating concentration of nicotine base (50 microM), and this effect was abolished by the nicotinic acetylcholine receptor (nAChR) blocker mecamylamine (100 microM). Taken together, these data suggest that the adverse effects of maternal smoking on sympathoadrenal function in the offspring are due in part to a loss or suppression of acute hypoxic sensitivity in adrenal chromaffin cells, triggered by the direct action of nicotine on endogenous nicotinic acetylcholine receptors.


[Quality Assurance in Sociomedical Evaluation by Peer Review: A Pilot Project of the German Statutory Pension Insurance].
The sociomedical evaluation by the German Pension Insurance serves the purpose of determining entitlement to disability pensions. A quality assurance concept for the sociomedical evaluation was developed, which is based on a peer Review process. Peer review is an established process of external quality assurance in health care. The review is based on a hierarchically constructed manual that was evaluated in this pilot project. The database consists of 260 medical reports for disability pension of 12 pension insurance agencies. 771 reviews from 19 peers were included in the evaluation of the inter-rater reliability. Kendall's coefficient of concordance W for more than 2 raters is used as primary measure of inter-rater reliability. Reliability appeared to be heterogeneous. Kendalls W varies for the particular criteria from 0.09 to 0.88 and reached for primary criterion reproducibility a value of 0.37. The reliability of the manual seemed acceptable in the context of existing research data and is in line with existing peer review research outcomes. Nevertheless, the concordance is limited and requires optimisation. Starting points for improvement can be seen in a systematic training and regular user meetings of the peers involved.


Identification of a consensus motif in Erg28p required for C-4 demethylation in yeast ergosterol biosynthesis based on mutation analysis.
The Erg28p protein is localized to the endoplasmic reticulum, where it acts as a scaffold to tether the C-4 demethylase complex involved in the sterol biosynthesis pathway of Saccharomyces cerevisiae. However, due to the challenges involved in characterizing the interactions of membrane proteins, the precise region of Erg28p that is responsible for the assembly of this enzyme complex remains unknown. To address this question, mutants with serial truncations in the C-terminus of Erg28p were constructed based on a topology prediction of its transmembrane domain. Sterol profiles demonstrated that intermediates involved in the stepwise removal of the two C-4 methyl groups from the tetracyclic sterol ring were accumulated in the ERG28Δ135-447 strain. Homologous alignment of Erg28p further identified a highly conserved 10-amino acid sequence (63LS/QARTFGT/LWT72) within the truncated region of ERG28Δ136-273. Complementation of the BY4741/erg28 strain with the ScERG28Δ175-204 plasmid resulted both in a significant growth inhibition and a reduction of ergosterol biosynthesis compared with the plasmid without the Δ175-204 truncation. Furthermore, homology modeling of the Erg28p mutant indicated that the deletion of residues 63-72 significantly disrupted the 3D structure of the four parallel helices in Erg28p. Taken together, the data indicate that the region spanning amino acids 63-72 constitutes a key consensus motif within Erg28p that is required for sterol C-4 demethylation during ergosterol biosynthesis in S. cerevisiae.


A method for correlating skin exposure to S-mustard vapor with skin damage.
An experimental procedure is described as a means for assessing the efficiency of skin-protecting measures against the vapors of hazardous substances. Bis(2-chloroethyl)sulfide (S-mustard) is used as the test substance. A continuous flow of S-mustard vapor is conducted through an exposure cell which is attached to the inner side of a rabbit's ear. From the difference in the concentrations measured before and behind the exposure cell, the absorption and the permeation rate of mustard into the skin is calculated. The skin damage, consisting of a reversible erythema, is quantified by measuring the optical transmittance of the exposed skin area during the following days and correlated with the respective absorption (dose) and exposure parameters (ct-product, with c = 3-50 ng/cm3 and t = 60 and 120 min). Reversible, i.e., completely healing, erythema are evoked by ct-products in the range of 250-2000 ng.min/cm3 corresponding to doses from about 0.1 to 1.1 micrograms/cm2. A comparison with older data reveals that human skin, in this respect, is about eight times more sensitive than the inner side of the rabbit's ear.


The levels, sources and reactivity of volatile organic compounds in a typical urban area of Northeast China.
Air concentrations of volatile organic compounds (VOCs) were continually measured at a monitoring site in Shenyang from 20 August to 16 September 2017. The average concentrations of alkanes, alkenes, aromatics and carbonyls were 28.54, 6.30, 5.59 and 9.78 ppbv, respectively. Seven sources were identified by the Positive Matrix Factorization model based on the measurement data of VOCs and CO. Vehicle exhaust contributed the most (36.15%) to the total propene-equivalent concentration of the measured VOCs, followed by combustion emission (16.92%), vegetation emission and secondary formation (14.33%), solvent usage (10.59%), petrochemical industry emission (9.89%), petrol evaporation (6.28%), and liquefied petroleum gas (LPG) usage (5.84%). Vehicle exhaust, solvent usage and combustion emission were found to be the top three VOC sources for O3 formation potential, accounting for 34.52%, 16.55% and 11.94%, respectively. The diurnal variation of the total VOCs from each source could be well explained by their emission characteristics, e.g., the two peaks of VOC concentrations from LPG usage were in line with the cooking times for breakfast and lunch. Wind rose plots of the VOCs from each source could reveal the possible distribution of the sources around the monitoring site. The O3 pollution episodes during the measurement period were found to be coincident with the elevation of VOCs, which was mainly due to the air parcel from the southeast direction where petrochemical industry emission was found to be dominant, suggesting that the petrochemical industry emission from the southeast was probably a significant cause of O3 pollution in Shenyang.


Long-term Results for Maxillomandibular Advancement to Treat Obstructive Sleep Apnea: A Meta-analysis.
To examine outcomes in the intermediate term (1 to <4 years), long term (4 to <8 years), and very long term (≥8 years) for maxillomandibular advancement (MMA) as treatment for obstructive sleep apnea (OSA). The Cochrane Library, Google Scholar, Embase, Cumulative Index to Nursing and Allied Health, and PubMed/MEDLINE. Three authors systematically reviewed the international literature through July 26, 2018. A total of 445 studies were screened, and 6 met criteria (120 patients). Thirty-one patients showed a reduction in apnea-hypopnea index (AHI) from a mean 48.3 events/h (95% CI, 42.1-54.5) pre-MMA to 8.4 (95% CI 5.6, 11.2) in the intermediate term. Fifty-four patients showed a reduction in AHI from a mean 65.8 events/h (95% CI, 58.8-72.8) pre-MMA to 7.7 (95% CI 5.9, 9.5) in the long term. Thirty-five showed a reduction in AHI from a mean 53.2 events/h (95% CI 45, 61.4) pre-MMA to 23.1 (95% CI 16.3, 29.9) in the very long term. Improvement in sleepiness was maintained at all follow-up periods. Lowest oxygen saturation improvement was maintained in the long term. The current international literature shows that patients with OSA who were treated with MMA maintained improvements in AHI, sleepiness, and lowest oxygen saturation in the long term; however, the mean AHI increased to moderate OSA in the very long term. Definitive generalizations cannot be made, and additional research providing individual patient data for the intermediate term, long term, and very long term is needed.


Magnetic assembly and patterning of general nanoscale materials through nonmagnetic templates.
Applied magnetic field represents an effective tool to rapidly assemble micro- and nanoscale magnetic objects into defined structures. Ordered assembly is typically achieved by using magnetic micropatterns, for which the downside is that they require advanced microfabrication techniques to produce. In addition, most conventional magnetic assembly strategies are restricted to target objects that possess magnetic properties. Herein we present a general strategy that allows convenient magnetically driven assembly of nonmagnetic objects in defined locations with high spatial resolution. The process involves immersing a polymer relief pattern in a uniformly magnetized ferrofluid, which modulates the local magnetic fields around the pattern. Nonmagnetic target objects dispersed in the same ferrofluid can then be magnetically assembled at positions defined by the polymer pattern. As the nonmagnetic polymer patterns can be conveniently fabricated at low cost through photolithography and soft-lithography processes, our method provides a general yet very effective means to assemble a wide range of nonmagnetic objects with controlled spatial distribution, paving the way toward patterning functional microstructures.


Histone demethylase KDM4A regulates adipogenic and osteogenic differentiation via epigenetic regulation of C/EBPα and canonical Wnt signaling.
Epigenetic modifications play a central role in cell differentiation and development. In the current study, we have recognized lysine demethylase 4A (KDM4A) as a novel epigenetic regulator of osteoblast and adipocyte differentiation. Kdm4a expression was upregulated during osteogenesis and adipogenesis of primary marrow stromal cells and established stromal ST2 line. Overexpression of wild-type Kdm4a promoted adipogenic differentiation and blocked osteogenic differentiation of the progenitor cells. This effect was largely alleviated when the catalytically dead mutation was made. Conversely, depletion or inactivation of Kdm4a in undifferentiated progenitor cells inhibited the formation of adipocytes and promoted the differentiation of osteoblasts. Mechanism explorations showed that overexpression of Kdm4a upregulated the expression of secreted frizzled-related protein 4 (Sfrp4) and CCAAT/enhancer-binding protein α (C/ebpα). Chromatin immunoprecipitation assay demonstrated that KDM4A directly bound the promoters of Sfrp4 and C/ebpα, removed the histone methylation mark H3K9me3, and reduced DNA methylation levels of CpG in promoter regions of C/ebpα and Sfrp4. Furthermore, overexpression of Kdm4a inactivated canonical Wnt signaling. Moreover, activation of canonical Wnt signaling through silencing of Sfrp4 in ST2 attenuated the inhibition of osteogenic differentiation and the enhancement of adipogenic differentiation by KDM4A. These data have identified KDM4A as a novel regulator of osteoblast and adipocyte differentiation and suggest KDM4A inhibition as a potential therapeutic target for treating metabolic disorders such as osteoporosis.


How the newly insured use health services: a lesson for the U.S. from Medicare.
The Congressional Budget Office estimates that about 32 million previously uninsured people will gain coverage by 2016, when health care reforms are fully implemented. But will these newly insured people use the health care system in the same ways as others? Is insurance enough to change patterns of use? The example of Medicare may provide some insight. This Issue Brief summarizes research that investigates how health care use and patterns change among the uninsured and insured once they gain Medicare coverage at age 65.


Goniometry of the proximal and distal interphalangeal joints, Part II: placement prefereces, interrater reliability, and concurrent validity.
The purposes of this repeated-measures single-case-design study were to describe goniometric placement preferences and their effect on the measurement of the proximal and distal interphalangeal joints, to determine interrater reliability, and to determine concurrent validity. Thirty-nine therapists measured one patient dorsally and laterally with the DeVore and the 6" clear goniometers. No significant differences were found between the two goniometers used in the study. Comparison of the means of lateral and dorsal measurements revealed that the only joint associated with a significant difference was the contracted index proximal interphalangeal joint (p=0.0347). Preferences did affect the standard deviations and ranges but not the means of the measurements. Interrater reliability was high (ICC 2,1: 0.99 and 0.86). Clinical and radiographic measurements were markedly different from each other (paired-difference t-tests), leading to inconclusive concurrent validity.


Occurrence of copper resistant mutants in the toxic cyanobacteria Microcystis aeruginosa: characterisation and future implications in the use of copper sulphate as algaecide.
Freshwater toxic cyanobacteria are an increasing problem to human and animal health. Control of cyanobacteria in water supply reservoirs involves the use of algaecides, such as copper sulphate, usually in a repetitive way. Repercussions of recurrent algaecide treatments on cyanobacteria population dynamics remain still unknown. We studied the adaptation of cyanobacteria to lethal doses of copper sulphate by using Microcystis aeruginosa as an experimental model. A fluctuation analysis demonstrated that copper-resistant cells arise by spontaneous mutations that occur randomly prior to exposition to copper sulphate. The rate of spontaneous mutation from copper sensitivity to resistance was 1.76 x 10(-6) mutants per cell division. Resistant mutants exhibited a diminished fitness in the absence of copper sulphate, but only these variants were able to grow at Cu(2+) concentrations higher than 5.8 microM. In addition, copper-resistant cells were significantly smaller than wild-type ones. Warnings on the long-term consequences of repetitive algaecide treatments in water supplies are suggested.