A Jovian Magnetodisc Model for the Juno Era.

The Jovian magnetosphere assumes a disc-like geometrical configuration ("magnetodisc") owing to the persistent presence of a system of azimuthal currents circulating in a washer-shaped volume aligned with, or near, the magnetic equatorial plane. A Voyager era empirical model of the magnetodisc is fitted to vector magnetic field measurements obtained during the Juno spacecraft's first 24 orbits. The best fitting (within 30 Jovian radii) magnetodisc model is characterized by an inner and outer radius of 7.8 and 51.4 Jovian radii, a half-thickness of 3.6 Jovian radii, with a surface normal at 9.3° from the Jovigraphic pole and 204.2° System 3 west longitude. We supplement the magnetodisc model with a second current system, also confined to the magnetic equatorial plane, consisting of outward radial currents that presumably effect the transfer of angular momentum to outward flowing plasma. Allowing for variation of the magnetodisc's azimuthal and radial current systems from one 53-day orbit to the next, we develop an index of magnetospheric activity that may be useful in interpretation of variations in auroral observations.

Prophylactic incisional negative pressure wound therapy reduces the risk of surgical site infection after caesarean section in obese women: a pragmatic randomised clinical trial.

OBJECTIVE: To evaluate the reduction of surgical site infections by prophylactic incisional negative pressure wound therapy compared with standard postoperative dressings in obese women giving birth by caesarean section. DESIGN: Multicentre randomised controlled trial. SETTING: Five hospitals in Denmark. POPULATION: Obese women (prepregnancy body mass index (BMI) ≥30 kg/m2 ) undergoing elective or emergency caesarean section. METHOD: The participants were randomly assigned to incisional negative pressure wound therapy or a standard dressing after caesarean section and analysed by intention-to-treat. Blinding was not possible due to the nature of the intervention. MAIN OUTCOME MEASURES: The primary outcome was surgical site infection requiring antibiotic treatment within the first 30 days after surgery. Secondary outcomes included wound exudate, dehiscence and health-related quality of life. RESULTS: Incisional negative pressure wound therapy was applied to 432 women and 444 women had a standard dressing. Demographics were similar between groups. Surgical site infection occurred in 20 (4.6%) women treated with incisional negative pressure wound therapy and in 41 (9.2%) women treated with a standard dressing (relative risk 0.50, 95% CI 0.30-0.84; number needed to treat 22; P = 0.007). The effect remained statistically significant when adjusted for BMI and other potential risk factors. Incisional negative pressure wound therapy significantly reduced wound exudate whereas no difference was found for dehiscence and quality of life between the two groups. CONCLUSION: Prophylactic use of incisional negative pressure wound therapy reduced the risk of surgical site infection in obese women giving birth by caesarean section. TWEETABLE ABSTRACT: RCT: prophylactic incisional NPWT versus standard dressings postcaesarean in 876 women significantly reduces the risk of SSI.

Cost-effectiveness of incisional negative pressure wound therapy compared with standard care after caesarean section in obese women: a trial-based economic evaluation.

OBJECTIVE: To evaluate the cost-effectiveness of incisional negative pressure wound therapy (iNPWT) in preventing surgical site infection in obese women after caesarean section. DESIGN: A cost-effectiveness analysis conducted alongside a clinical trial. SETTING: Five obstetric departments in Denmark. POPULATION: Women with a pregestational body mass index (BMI) ≥30 kg/m2 . METHOD: We used data from a randomised controlled trial of 876 obese women who underwent elective or emergency caesarean section and were subsequently treated with iNPWT (n = 432) or a standard dressing (n = 444). Costs were estimated using data from four Danish National Databases and analysed from a healthcare perspective with a time horizon of 3 months after birth. MAIN OUTCOME MEASURES: Cost-effectiveness based on incremental cost per surgical site infection avoided and per quality-adjusted life-year (QALY) gained. RESULTS: The total healthcare costs per woman were €5793.60 for iNPWT and €5840.89 for standard dressings. Incisional NPWT was the dominant strategy because it was both less expensive and more effective; however, no statistically significant difference was found for costs or QALYs. At a willingness-to-pay threshold of €30,000, the probability of the intervention being cost-effective was 92.8%. A subgroup analysis stratifying by BMI shows that the cost saving of the intervention was mainly driven by the benefit to women with a pre-pregnancy BMI ≥35 kg/m2 . CONCLUSION: Incisional NPWT appears to be cost saving compared with standard dressings but this finding is not statistically significant. The cost savings were primarily found in women with a pre-pregnancy BMI ≥35 kg/m2 . TWEETABLE ABSTRACT: Prophylactic incisional NPWT reduces the risk of SSI after caesarean section and is probably dominant compared with standard dressings #healtheconomics.

The half-life and exposure of cefuroxime varied in newborn infants after a Caesarean section.

AIM: No information was available on how fast intravenous cefuroxime administered to pregnant women before a Caesarean section was cleared in newborn infants. This study investigated the drug's half-life and the exposure of healthy newborn infants after their mothers received the drug. METHODS: Healthy mothers received a single dose of cefuroxime 15-60 minutes before skin incision. One blood sample was drawn from the umbilical cord, and two blood samples were drawn from the infant after delivery. Total plasma cefuroxime (µg/mL) was measured using high-pressure liquid chromatography. RESULTS: Cefuroxime was given to 22 mothers, including two who had twins. The concentration of cefuroxime varied significantly among infants (p < 0.001), while the rate of decline did not (p = 0.24). The median cefuroxime half-life was 3.5 hours (range 2.9-5.5), which was approximately three times longer than in normal adults and seemed to clear within 24 hours. The median area under the concentration-time curve was 65.0 hour µg/mL (range 31.7-162.4). CONCLUSION: We found that the cefuroxime half-life after a Caesarean section varied among infants and was longer than in normal adults but cleared within 24 hours. Exposure to cefuroxime in newborn infants may influence the gut microbiota and should be investigated further.

Meta-analysis of negative-pressure wound therapy for closed surgical incisions.

BACKGROUND: Postoperative wound complications are common following surgical procedures. Negative-pressure wound therapy (NPWT) is well recognized for the management of open wounds and has been applied recently to closed surgical incisions. The evidence base to support this intervention is limited. The aim of this study was to assess whether NPWT reduces postoperative wound complications when applied to closed surgical incisions. METHODS: This was a systematic review and meta-analysis of randomized clinical trials of NPWT compared with standard postoperative dressings on closed surgical incisions. RESULTS: Ten studies met the inclusion criteria, reporting on 1311 incisions in 1089 patients. NPWT was associated with a significant reduction in wound infection (relative risk (RR) 0·54, 95 per cent c.i. 0·33 to 0·89) and seroma formation (RR 0·48, 0·27 to 0·84) compared with standard care. The reduction in wound dehiscence was not significant. The numbers needed to treat were three (seroma), 17 (dehiscence) and 25 (infection). Methodological heterogeneity across studies led to downgrading of the quality of evidence to moderate for infection and seroma, and low for dehiscence. CONCLUSION: Compared with standard postoperative dressings, NPWT significantly reduced the rate of wound infection and seroma when applied to closed surgical wounds. Heterogeneity between the included studies means that no general recommendations can be made yet.

Pregestational body mass index is related to neonatal abdominal circumference at birth--a Danish population-based study.

OBJECTIVES: To examine the impact of maternal pregestational body mass index (BMI) and smoking on neonatal abdominal circumference (AC) and weight at birth. To define reference curves for birth AC and weight in offspring of healthy, nonsmoking, normal weight women. DESIGN: Population-based study. SETTING: Data from the Danish Medical Birth Registry. POPULATION: All live singletons without congenital malformations in Denmark 2004-10. METHODS: Data on 366,886 singletons at 35(+0) to 41(+6) weeks(+days) of gestation were extracted and analysed using multivariate linear regressions. MAIN OUTCOME MEASURES: Birth AC and weight in relation to pregestational maternal BMI, maternal smoking and medical conditions (any). RESULTS: Birth AC and weight increased with increasing pregestational BMI, and decreased with smoking (P < 0.0001). Reference curves were created for offspring of healthy, nonsmoking mothers with normal pregestational BMI. Mean AC ranged from 30.1 cm and 30.2 cm at 35 weeks of gestation to 33.9 cm and 34.1 cm at 41 weeks of gestation, for girls and boys, respectively. Mean birthweight ranged from 2581 and 2666 g at 35 weeks to 3705 and 3852 g at 41 weeks of gestation for girls and boys, respectively. Pregestational BMI correlated more to the Z score of birthweight than to the Z score of AC (P < 0.0001). CONCLUSION: Birth AC and weight are affected by maternal smoking status and pregestational BMI. Pregestational BMI correlated more to birthweight than to AC. Using data from healthy, nonsmoking mothers with normal pregestational BMI we have provided new reference curves for birth AC and birthweight.

Relaxant effect of a novel calcium-activated potassium channel modulator on human myometrial spontaneous contractility in vitro.

AIM: To investigate the effect of 4,5-dichloro-1,3-diethyl-1,3-dihydro-benzoimidazol-2-one (NS4591), a novel SK/IK channels positive modulator, on human myometrial activity. METHODS: Organ bath studies were performed on myometrial preparations obtained from women undergoing elective caesarean section at term (N = 11) or hysterectomy (N = 11). NS4591 was added cumulatively in the concentration range of 0.3-30 µm. In separate experiments, the effects of pre-incubation of muscle preparation with the SK or IK channel blockers apamin (1 µm) and TRAM34 (10 µm) on the outcomes of NS4591 were evaluated. Simultaneous vehicle controls were performed for all experiments. The effects of drugs were studied on spontaneous contractions. RESULTS: NS4591 exerted an inhibitory effect on myometrial contractions in muscle strips from non-pregnant and pregnant women. The contractility in non-pregnant and pregnant myometrium was reduced to the following values respectively: amplitude 20.65 ± 7.38% (P < 0.001) and 42.85 ± 11.04% (P < 0.05) and area under the curve 11.72 ± 7.39% (P < 0.001) and 34.84 ± 10.50% (P < 0.001) and are reflective of 30 µm NS4591 compared to vehicle control. In non-pregnant tissue, apamin partially reduced the inhibitory effects of NS4591, but we observed relaxation mediated by NS4591 despite pre-incubation with TRAM34. In contrast, in pregnant tissue, neither apamin nor TRAM34 could reverse the relaxatory effects of NS4591. CONCLUSION: Our findings imply that SK/IK channels are present and functional in myometrium from pregnant and non-pregnant women. The SK/IK channel-positive modulator NS4591 exerts relaxation of human myometrium in vitro, and this may have implications for the clinical management of preterm labour.

Severe hypothyroidism due to atrophic thyroiditis from second year of life influenced developmental outcome.

UNLABELLED: From the second year of life a girl showed an insidious development of clinical hypothyroidism due to a non-goitrous lymphocytic thyroiditis without traceable circulating levels of thyroid antibodies measured by routine immunoassays. The diagnostic delay of this rare variant of atrophic thyroiditis caused persistent neuropsychological deficits. CONCLUSION: Her difficulties with speed of processing and working memory in particular could suggest a frontal deficit, possibly in the dorsolateral prefrontal circuit. This contrasts with findings in congenital hypothyroidism, suggesting a relatively preserved frontal function, and could illustrate different neuropsychological deficits of hypothyroidism at different ages in early childhood.

Personality disorders in a total population twin cohort with eating disorders.

Findings regarding the occurrence of personality disorders (PDs) in eating disorders (EDs) have been contradictory. Most previous studies have been clinic-based. The aims of the current study were to assess the prevalence of PD in ED in a population-based twin group and to establish the distribution of PD in three subgroups of ED. A two-step screening and diagnostic study of ED was performed in a large Danish twin population. Axis I and axis II DSM-III-R and DSM-IV ED diagnoses were made on the basis of results obtained at clinical investigations and interviews. Forty-nine percent of the participants with ED had at least one PD, compared to 26% in those with no ED (P <.001). Cluster C PD was the most common type of PD in all subgroups of ED, and cluster B PD was found only in participants with bulimic symptoms. Genetic factors appeared to contribute significantly to the variance of cluster C PD in ED, which was evaluated as a possibly important background factor in ED.

Aromatic quinolinecarboxamides as selective, orally active antibody production inhibitors for prevention of acute xenograft rejection.

The prevention of xenograft rejection is substantially dependent on inhibiting antibodies (Ab) produced by B-cells independently of T-cell signals (TI-1). Due to their ubiquitous biochemical mechanisms of action, the immunosuppressants currently employed not only fail to discriminate between B- and T-cells but also have a narrow therapeutic window and, thus, their prolonged use in complex immunosuppressive regimens is problematic. By capitalizing on the target enzyme-bound (DHODH) structure 1b of one of these compounds, leflunomide, and modulating part of its multiple mechanisms of action to gain selectivity, the quinoline-8-carboxamide 3 was designed as a potentially weak enzyme inhibitor but effective immunosuppressant. Compound 3 fulfilled the mechanistic criteria set and had 10-fold B-cell over T-cell selectivity. Its pyridyl analogue 4 was found to be a highly potent and selective B-cell immunosuppressant with a 75-fold selectivity for B- over T-cells (as judged by the MLR data) and no general cytotoxicity at concentrations up to 160-fold higher than those required to inhibit B-cells. In the mouse, 4 effectively blocked TI-1 Ab production and suppressed Ab-mediated xenograft rejection in a xenotransplantation model under a once-daily dosing regimen, with efficacy down to 0.3 mg/kg/day po. These are the first data demonstrating the feasibility of the development of drugs specific for impeding Ab production.

A preliminary population-based twin study of self-reported eating disorder.

BACKGROUND: Twin studies have concluded that there is a substantial genetic contribution to the aetiology of eating disorders. The aim of the present study was to estimate the genetic contribution to the aetiology of self-reported eating disorders in a sample of representative twins. METHOD: A population cohort of 34142 young Danish twins was screened for eating disorders by a mailed questionnaire. RESULTS: Concordance rates differed significantly across monozygotic and dizygotic twin pairs for broadly defined self-reported anorexia nervosa and bulimia nervosa. Heritability estimates of 0.48, 0.52 and 0.61 respectively were estimated for narrow and broad definitions of self-reported anorexia nervosa and for self-reported bulimia nervosa. CONCLUSIONS: There is a genetic contribution to the aetiology of self-reported eating disorders in the general population. The relationship between self-reported and clinical eating disorder remains to be examined.

Short-chain fatty acids stimulate mucosal cell proliferation in the closed human rectum after Hartmann's procedure.

Hartmann's procedure in humans results in a closed rectum deprived of its natural short-chain fatty acid source. This induces atrophy of the entire rectal wall. Ki-67 is a monoclonal antibody directed towards proteins in the cell nucleus that are present only during cell proliferation. This study investigated the effects of short-chain fatty acids on mucosal cell proliferation in the human rectum after Hartmann's procedure by means of Ki-67. Eight patients in whom Hartmann's procedure was performed were treated with placebo and then short-chain fatty acids for 14 days. Biopsies specimens were taken from the rectum before and after treatment; these were prepared with Ki-67 and labeling index was determined. The treatment was found significantly to increase proliferative activity in the rectal mucosa (P<0.01); the increase was principally in the middle (P<0.01) and upper crypt (P<0.05) compartments.

Contribution of CD40-CD154-mediated costimulation to an alloresponse in vivo.

BACKGROUND: Costimulation through CD40-CD154 plays an important role in T-cell activation. Although systemic administration of anti-CD154 antibody prevents or delays rejection of organ allografts in animal models, the molecular mechanisms responsible for this effect are not well defined. METHODS: We have previously demonstrated that priming of mice (H2d) with CD40-/- but not with wildtype naive B cells (H2b) leads to alloantigen-specific T-cell hyporesponsiveness in vitro. In the present study, we investigated whether such priming modifies allograft rejection in a major histocompatibility complex-mismatched murine cardiac transplantation model. RESULTS: Priming of hosts with donor-specific CD40-/- B cells delayed rejection of subsequently transplanted wild-type cardiac allografts by 8.0 days (P<0.001). The lack of CD40 on the cardiac graft delayed rejection in unprimed or primed hosts by 3-5 days. Prolongation of graft survival correlated with the failure of infused CD40-/- B cells to express B7.2 and ICAM-1 in vivo. CONCLUSIONS: Our data suggest that CD40-CD154 costimulation contributes to T cell priming to alloantigens in vivo and to a second set rejection phase in which donor antigens are presented to primed T cells.

Contribution of donor-specific antibodies to acute allograft rejection: evidence from B cell-deficient mice.

BACKGROUND: The role of T lymphocytes in acute allograft rejection is well established. The involvement of B lymphocytes in this process, however, is more controversial. A series of reports showed that mice without a functional B-cell compartment rejected allografts with the same kinetics as control animals. In rats, however, alloantibodies were found to play a decisive role in allograft rejection. To provide an explanation for the discrepant results, we readdressed the role of B cells and antibodies in mice with disrupted immunoglobulin mu chain genes. The use of cyclosporine (CsA), which strongly suppresses T cells, allowed us to focus specifically on the function of B cells. METHODS: C57BL/6 mice rendered B cell deficient by targeted disruption of the immunoglobulin mu chain gene (referred to as microMT/microMT mice) and microMT/+ control mice with one functional mu chain were heterotopically transplanted with fully MHC-disparate BALB/c hearts. CsA was administered subcutaneously by Alzet osmotic pumps. Normal and immune serum specific for donor hearts was given to assess the role of antibodies in the rejection process. RESULTS: Both B cell-deficient microMT/microMT and heterozygous microMT/+ mice were found to reject transplanted hearts within a similar period of time. In contrast, when T cells were partially suppressed with CsA, graft survival was significantly prolonged in microMT/microMT mice as compared with heterozygous controls. Passive transfer of donor-specific immune serum, obtained from microMT/+ animals rejecting allogeneic hearts, to CsA-treated microMT/microMT mice significantly accelerated allograft rejection as opposed to recipients treated with normal serum. CONCLUSIONS: B lymphocytes and antibodies play an important role in acute allograft rejection particularly when the dominant T-cell compartment is partially suppressed.

Allo- and autotransplantation of carotid artery--a new model of chronic graft vessel disease: evaluation by magnetic resonance imaging and histology.

BACKGROUND: Graft vessel disease is a special form of accelerated arteriosclerosis. Because immunological and nonimmunological factors can contribute to graft vessel disease, we developed a model that enables the study of both factors simultaneously. METHODS: A carotid artery was allografted from DA to Lewis rats, with the excised native artery autografted on the contralateral side. Five groups of six to seven rats were treated for 8 weeks with vehicle (placebo) or cyclosporine (CsA) (0.3, 1, 3, and 10 mg x kg(-1) x day(-1)), which was administered using subcutaneous osmotic minipumps. The carotid lumen area was estimated in vivo at 2, 4, and 8 weeks by magnetic resonance imaging (MRI); CsA blood levels were determined twice. Carotid neointimal thickening and medial and luminal area were measured with histological techniques. RESULTS: MRI showed bulging of the allografts but not autografts. Bulging disappeared over time with narrowing of the allograft lumina estimated by both MRI and histology. Histologically, vehicle-treated animals developed a massive neointima, which was inhibited in a dose-dependent manner by CsA. Autografts remained normal except for minimal subintimal thickening of two of four arteries in the group given the highest dose of CsA. Cellular rejection was detected in the allografts of all but the highest-dose group. The CsA blood levels were similar to those used in man at the two lower doses and about 10-fold higher at the highest dose. CONCLUSIONS: Subintimal thickening did not correlate with in vivo lumen size, a phenomenon that we have previously described for balloon catheter-induced lesions. CsA blood concentrations similar to those used in patients suppressed neointima formation in part, and 10-fold higher concentrations almost completely suppressed neointima formation.

SDZ RAD, a new rapamycin derivative: synergism with cyclosporine.

BACKGROUND: SDZ RAD is a new rapamycin analog with potent immunosuppressive activity. Compounds of the rapamycin class differ in their mode of action from cyclosporine, thus providing a rationale for potential synergism of these two potent immunosuppressants. METHODS: The two-way mouse mixed lymphocyte reaction (BALB/c-CBA strain combination) was applied. Orthotopic kidney and heterotopic heart allografting was performed in the stringent DA-to-Lewis rat strain combination, with administration of compounds orally as microemulsion preconcentrate (i.e., Neoral in the case of cyclosporine). RESULTS: Isobologram analysis of checkerboard titrations of SDZ RAD and cyclosporine in two-way mouse mixed lymphocyte reactions indicates a synergistic interaction in vitro. In vivo, the minimal effective dose of microemulsion cyclosporine giving long-term graft survival was 5.0 mg/kg/day; for SDZ RAD, the minimal effective dose was 5.0 mg/kg/day in kidney transplantation and >5.0 mg/kg/day in heart transplantation. Long-term allograft survival was noted for combinations of microemulsion cyclosporine administered at 1.0 or 2.0 mg/kg/day and SDZ RAD given at between 0.5 and 2.0 mg/kg/day. The index of synergy in different combinations ranged between 0.3 and 0.7. CONCLUSIONS: SDZ RAD and cyclosporine show synergism in immunosuppression, both in vitro and in vitro. They form a promising synergistic drug combination in allotransplantation.

Magnetic resonance imaging for the evaluation of rejection of a kidney allograft in the rat.

Orthotopic DA (RT1a) into Lewis (RT1l) rat kidney allografts and control Lewis-into-Lewis grafts were assessed by magnetic resonance imaging (MRI) and perfusion measurement after intravenous injection of a superparamagnetic contrast agent. MRI anatomical scores (range 1-6) and perfusion rates were compared with graft histology (rank of rejection score 1-6). Not only acute rejection, but also chronic events were monitored after acute rejection was prevented by daily cyclosporine (Sandimmune) treatment during the first 2 weeks after transplantation. In acute allograft rejection (n = 11), MRI scores reached the maximum value of 6 and perfusion rates were severely reduced within 5 days after transplantation; histology showed severe acute rejection (histologic score 5-6). In the chronic phase (100-130 days after transplantation), allografts (n = 5) manifested rejection (in histology cellular rejection and vessel changes), accompanied by MRI scores of around 2-3 and reduced perfusion rates. Both in the acute and chronic phases, the MRI anatomical score correlated significantly with the histological score (Spearman rank correlation coefficient rs 0.89, n = 30, P < 0.01), and perfusion rates correlated significantly with the MRI score or histological score (rs values between -0.60 and -0.87, n = 23, P < 0.01). It is concluded that MRI represents an interesting tool for assessing the anatomical and hemodynamical status of a kidney allograft in the acute and chronic phases after transplantation.