Pneumococcal antibody protection in patients with autoimmune inflammatory rheumatic diseases with varying vaccination status.

Objectives: The aims of this cross-sectional study were to assess the pneumococcal antibody coverage in patients with autoimmune inflammatory rheumatic disease (AIRD) and to identify predictors associated with inadequate protective antibody levels. Method: Antibodies to 12 serotypes occurring in the commonly applied pneumococcal vaccines in Denmark were measured in AIRD patients with a diagnosis of rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis attending the Department of Rheumatology at the North Denmark Regional Hospital. Immunization against pneumococcal infection was defined as a geometric mean level ≥ 1 µg antibodies/mL. Clinical information about vaccination status and disease/treatment history was retrieved from the medical file system. Results: Results of antibody measurement and vaccination status were available from 346 AIRD patients, of whom 200 (58%) were registered as receiving pneumococcal vaccination, whereas the remaining 146 patients (42%) were not. Of all 346 patients, only 61 (18%) were measured with an adequate level of protective antibodies (30% vs 1%, respectively). Methotrexate treatment at the time of vaccination and increasing age were identified as predictors of poor vaccination outcome in multiple logistic regression analysis. Conclusions: This post-vaccination study showed that less than one-fifth of the AIRD patients are adequately protected against pneumococcal infection, although the immunization programme had been implemented in more than half of the study population. Development of improved vaccination strategies is required to achieve a higher immunization coverage rate and more efficient lasting antibody response.

Feature domain-specific movement intention detection for stroke rehabilitation with brain-computer interfaces.

Brain-computer interface (BCI) driven electrical stimulation has been proposed for neuromodulation for stroke rehabilitation by pairing intentions to move with somatosensory feedback from electrical stimulation. Movement intentions have been detected in several studies using different techniques, with temporal and spectral features being the most common. A few studies have compared temporal and spectral features, but conflicting results have been reported. In this study, the aim was to investigate if complexity measures can be used for movement intention detection and to compare the detection performance based on features extracted from three different domains (time, frequency and complexity) from single-trial EEG. Two data sets were used where four different isometric palmar grasps or dorsiflexions were performed while continuous EEG was recorded. 39 healthy subjects performed or imagined these movements and 11 stroke patients attempted to perform the movements. The EEG was pre-processed and divided into two epoch classes: Background EEG (2 s) and movement intention (2 s). To obtain an estimated detection performance, temporal, spectral and complexity features were extracted and classified (linear discriminant analysis) after the feature vector was reduced using sequential forward selection. The results show that accuracies between 82-87% and 74-80% are obtained for foot and hand movements, respectively. The temporal feature domain was the most dominant for foot movement intention detection, while the spectral features contributed more to the hand movement detection. The complexity features could be used to detect movement intentions, but the performance was much lower compared to temporal and spectral features.

The effect of Lactobacillus paracasei subsp. paracasei L. casei W8® on blood levels of triacylglycerol is independent of colonisation.

Gut microbiota (GM) dysbiosis has been linked to obesity and its metabolic complications such as cardiovascular disease (CVD). The risk of developing CVD increases with elevated concentration of serum triacylglycerol (TAG). In a blinded, randomised two-arm parallel human intervention study we have previously found that four weeks of supplementation with Lactobacillus paracasei subsp. paracasei L. casei W8® (L. casei W8) compared to placebo reduced the concentration of TAG in 64 young healthy adults, an effect, likely mediated by a decreased stearoyl- CoA desaturase-1 (SCD1) activity. In the present study we analysed faecal samples obtained during the intervention study to investigate whether this effect was related to the ability of L. casei W8 to colonise the human gut after supplementation of L. casei W8 (1010 cfu daily) as determined by qPCR specific for L. paracasei and L. casei (L. casei group); whether L. casei W8 consumption affected GM composition as determined by 16S rRNA gene targeted 454/FLX amplicon sequencing; and whether these changes were associated with changes in TAG concentration and SCD1 activity. Faecal samples were collected at baseline, after four weeks supplementation and two weeks after the supplementation was ended, and fasting blood samples were collected at baseline and after 4 weeks. Four weeks supplementation with L. casei W8 did not affect the overall composition of the GM; however, an increase in the relative abundance of the L. casei group from 8.48×10-6% of the total GM compared to 2.83×10-3% at baseline (P<0.001) was observed. Two weeks after supplementation ended, the relative abundance of the L. casei group was still increased 14 times compared to before the intervention (P<0.01). However, neither the increase in the abundance of the L. casei group nor overall GM composition correlated with changes in blood lipids or SCD1 activity.

TLR-mediated B cell activation results in ectopic CLIP expression that promotes B cell-dependent inflammation.

Infectious pathogens produce compounds called Toll ligands that activate TLRs on lymphocytes. Acute activation triggered by certain TLRs appears to "jump start" the innate immune response, characterized by the release of inflammatory cytokines and cellular expansion. In some individuals, there is a failure to control acute inflammation, resulting in postinfectious, chronic inflammation. Susceptibility to chronic inflammation is strongly associated with an individual's MHC genes. Recent clinical trials for several autoimmune diseases characterized by chronic inflammation suggest that B lymphocyte depletion therapies dampen chronic immune activation. However, currently, there is no known mechanism that accounts for the correlation among TLR activation, MHC genetics, and a pathological role for B-lymphocytes. Our hypothesis is that TLR-activated B cells (B cells that have been polyclonally activated in the absence of antigen-specific signals) are not controlled properly by T cell-dependent B cell death, thereby causing B cell-dependent chronic inflammation. Here, we show that treatment with Toll ligands results in polyclonal B cell activation accompanied by ectopic expression of CLIP. Furthermore, by adoptively transferring purified CLIP+ B cells in syngeneic animals, we find that CLIP+ B cells induce production of TNF-α by host T cells. Finally, we demonstrate that CLIP-targeted peptide competition results in the death of polyclonally activated CLIP+ B cells.

Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy.

OBJECTIVE: Menopause is linked to an increase in fat mass and a decrease in lean mass exceeding age-related changes, possibly related to reduced output of ovarian steroids. In this study we examined the effect of combined postmenopausal hormone replacement therapy (HRT) on the total and regional distribution of fat and lean body mass. RESEARCH METHODS AND PROCEDURES: Sixteen healthy postmenopausal women (age: 55 +/- 3 years) were studied in a placebo-controlled, crossover study and were randomized to 17beta estradiol plus cyclic norethisterone acetate (HRT) or placebo in two 12-week periods separated by a 3-month washout. Total and regional body composition was measured by DXA at baseline and in the 10th treatment week in both periods. Changes were compared by a paired Student's t test. RESULTS: The change in body weight during HRT was equal to the change during placebo (-24.6 g vs. -164 g, p = 0.42), but relative fat mass was significantly reduced (-0.5% vs. +1.24%, p < 0.01). During HRT, compared with during placebo, lean body mass increased (+347 g vs. -996 g, p < 0.01) and total fat mass decreased (-400 g vs. +836 g, p = 0.06). Total bone mineral content increased (+28.9 g vs. -4.4 g, p = 0.04) and abdominal fat decreased (-185 g vs. +253 g, p = 0.04) during HRT compared with placebo. DISCUSSION: HRT is linked to the reversal of both menopause-related obesity and loss of lean mass, without overall change in body weight. The increase in lean body mass during HRT is likely explained by muscle anabolism, which in turn, prevents disease in the elderly.

Polycomb group genes control pattern formation in plant seed.

Transcriptional activators of the Trithorax group (TRX-G) and repressors of the Polycomb group (Pc-G) are involved in multiple aspects of embryogenesis in Drosophila and the mouse [1, 2] and appear to have a conserved role in the zygotic control of the development of the anterior-posterior axis [3, 4, 5]. In the model plant Arabidopsis, three Pc-G genes have been isolated and characterized to date. CURLY LEAF (CLF) represses the expression of a floral homeotic gene in vegetative tissues but does not appear to have a role in plant embryogenesis [6]. Two other Pc-G genes, FIS1/MEDEA [7, 8, 9], and FIS3/FIE [8, 10] have been characterized in studies of mutants that produce seeds in the absence of fertilization. Seeds resulting from autonomous development in fis mutants do not contain an embryo but only endosperm, the second product of double fertilization in flowering plants [11, 12]. Thus, FIS genes are considered to be repressors of endosperm development before fertilization. We report that when fis ovules are fertilized, the endosperm patterning along the major polar axis is perturbed. Posterior structures develop in more anterior domains of the endosperm. This correlates with the ectopic expression of a posterior molecular marker. FIS genes appear to be potent regulators of the establishment of the anterior-posterior polar axis in the endosperm.

Temporal changes in cardiac function and cerebral blood flow during sequential postmenopausal hormone replacement.

OBJECTIVE: The purpose was to assess the temporal changes in cardiac function and cerebral blood flow during postmenopausal administration of estrogen with and without progestogen. STUDY DESIGN: Sixteen postmenopausal volunteers were assessed during estradiol plus sequential norethindrone acetate and placebo in two 12-week periods. Temporal changes were measured by magnetic resonance flow mapping 8 times. RESULTS: Systemic vascular resistance was reduced during estradiol (-6.9%; P <.05), declined further during the addition of norethindrone acetate, and was accompanied by an increase in stroke volume (maximum increase, 5.2%; P <.05) without fluid retention. Both systolic (-5 mm Hg; P =.03) and diastolic (-3 mm Hg; P =.03) blood pressure were reduced during estradiol. Cerebral blood flow was reduced after 9 weeks of hormone replacement therapy (-37 mL/min; P =.01) but increased to baseline after the addition of norethindrone acetate. CONCLUSIONS: Sequential hormone replacement therapy is associated with changes in cardiac function, which are of therapeutic potential in cardiovascular disorders. Sequential hormone replacement therapy exhibits an overall neutral effect on cerebral blood flow.

Temporal changes in clinic and ambulatory blood pressure during cyclic post-menopausal hormone replacement therapy.

OBJECTIVE: Post-menopausal hormone replacement (HRT) might protect against cardiovascular disease, possibly by arterial vasodilation and reduced blood pressure. Progestogens are needed to avoid endometrial disease but vascular effects are controversial. The objective was to assess temporal changes in blood pressure (BP) by two measurement techniques during a cyclic hormone replacement regimen. DESIGN AND METHODS: Sixteen healthy and normotensive post-menopausal women (age 55 +/- 3 years) were studied in a placebo-controlled, randomized crossover study, and were randomized to 17beta-oestradiol plus cyclic norethisterone acetate (NETA) or placebo in two 12-week periods separated by a 3-month washout Clinic blood pressure was measured sitting by the same observer with a mercury manometer at four visits in each period. Twenty-four hour ambulatory blood pressure was measured at baseline and in the ninth weeks of treatment in both periods. RESULTS: Clinic systolic and diastolic BP were reduced after 10 days of oestradiol (-5.1 and -3.2 mmHg respectively, P < or = 0.05). After 9 weeks of cyclic HRT, prior to progestogen addition, clinic BP returned to baseline. During addition of NETA, diastolic blood pressure was again reduced (-3.6 mmHg, P= 0.037). Mean 24 h ambulatory systolic and diastolic blood pressures were significantly lower than clinic measurements (-15.7 and -5.9 mmHg, P < 0.001) but were unaffected by HRT. CONCLUSIONS: Clinic blood pressure is reduced during a cyclic HRT regimen but the reduction varies with the HRT regimen, which might explain the diversity in previous BP findings during HRT. Norethisterone acetate might possess additive blood pressure-lowering effects in postmenopausal women.

Differences between users and non-users of emergency contraception after a recognized unprotected intercourse.

Knowledge of emergency contraception is crucial but might not transform into use. Factors influencing decision-making related to use of emergency contraception after an unprotected intercourse and the characteristics of users of emergency contraception (EC) were assessed. In an abortion clinic setting, 217 women referred for termination of pregnancy were asked to fill in a questionnaire. Of the 217 women, 139 (64%) were aware of pregnancy risk but only 9 (4%) had used EC after the unprotected intercourse. 42% were estimated to have sufficient knowledge to use hormonal emergency contraception. In a larger background population, a calculated 29% used EC after a recognized unprotected intercourse. EC users were older, better educated, more often in stable relationships, had experienced more abortions, and gestation age was less. However, younger women were in general better informed of EC. Knowledge of EC does not necessarily transform into action. Neglect of risk after an unprotected intercourse is frequent in younger well-informed women and information has to be better targeted.

Zinc, magnesium and calcium in human seminal fluid: relations to other semen parameters and fertility.

The effects of zinc, magnesium and calcium in seminal plasma on time-to-pregnancy (TTP) in healthy couples, on conventional semen parameters and computer-assisted semen analysis (CASA) parameters were evaluated. The localization of chelatable zinc ions in seminal plasma and spermatozoa were assessed by autometallography (AMG). Differences in chelatable zinc localization in samples with high and low total zinc were evaluated. Semen samples from 25 couples with short TTP and 25 couples with long TTP were subjected to conventional semen analysis, CASA, zinc and magnesium measurements by inductively coupled plasma mass spectrometry, and calcium by flame atomic absorption spectrometry. The cations were strongly inter-correlated, but no correlation with TTP or conventional semen parameters was found. Semen samples with high zinc concentrations exhibited statistically significant poorer motility assessed by the CASA parameters straight line velocity and linearity than samples with low zinc content. Calcium concentration also showed statistically significant differences for the same parameters, but the effect was removed by entering zinc concentration into a multiple regression model. Semen samples with high total zinc exhibited stronger staining of the seminal plasma at AMG. It is suggested that high seminal zinc concentrations have a suppressing effect on progressive motility of the spermatozoa ('quality of movement'), but not on percentage of motile spermatozoa ('quantity of movement').

Chelation of intracellular zinc ions affects human sperm cell motility.

The effects of two different zinc chelators, diethyldithiocarbamate (DEDTC) and calcium ethylenediaminetetraacetic acid (EDTA), in full semen samples and 'swim-up' samples were investigated. DEDTC, which crosses cell membranes, and EDTA, which does not cross cell membranes, were added to semen samples in different concentrations. Sperm cell motility parameters were assessed by computer-assisted semen analysis (CASA). It was found that very small concentrations (0.01 mM) of DEDTC immobilized the sperm cells within 80 min, while EDTA had no depressing effect at the concentrations used. In full semen samples EDTA enhanced straight line velocity (VSL) at concentrations of 1.0 and 0.5 mM; this effect was not found at higher concentrations. It is suggested that intracellular mitochondrial zinc ions play a crucial role for sperm cell motility, while loosely bound or free zinc ions in the seminal plasma exert a secondary role on human sperm cell motility.

Prognostic implications of ventricular ectopy one week, one month, and sixteen months after an acute myocardial infarction. Danish Study Group on Verapamil in Myocardial Infarction.

BACKGROUND: Ventricular ectopy early after an acute myocardial infarction (AMI) has previously been demonstrated to predict mortality. Less information is available about the prognostic implications of ventricular ectopy occurring late after an AMI, and no information is available about the prognostic implication of the development of ventricular ectopy during the first year after an AMI. HYPOTHESIS: The purpose of the present prospectively conducted trial, a part of the Danish Verapamil Infarction Trial II (DAVIT II), was to evaluate the prognostic implication of (1) ventricular premature complexes (VPCs) recorded by 24-h Holter monitoring 1 week, 1 month, and 16 months after an AMI; and (2) development of > 10 VPCs/h or of any complex ventricular ectopy, that is, pairs, more than two types of VPCs, ventricular tachycardia, or > 10 VPCs/h during follow-up after an AMI. METHODS: Patients were monitored 1 week (n = 250), 1 month (n = 210), and 16 months (n = 201) after AMI. RESULTS: Multivariate analyses based on history, clinical findings, and ventricular ectopy showed the following results: After 1 week, > 10 VPCs/h (p = 0.0006) and heart failure (p < 0.007); after 1 month, > 10 VPCs/h (p = 0.003) and resting heart rate (p < 0.02); and after 16 months, ventricular tachycardia (p = 0.002) independently predicted long-term mortality. Mortality was significantly predicted by the development of > 10 VPCs/h from 1 week to 1 month (p = 0.003) and 16 months (p = 0.03), and from 1 to 16 months (p = 0.007) after AMI, as well as by the development of any complex ventricular ectopy from 1 week to 1 month (p = 0.02) and 16 months (p = 0.01), and from 1 to 16 months (p = 0.04) after AMI. CONCLUSION: The present study demonstrated that 1 week and 1 month after an AMI the quantity of VPCs, that is, > 10 VPCs/h, predicted mortality, whereas 16 months after an AMI the quality of VPCs, that is, ventricular tachycardia, predicted mortality.

Whipple's operation for carcinoma of the pancreatic head and the ampullary region. Short-and long-term results.

BACKGROUND AND METHODS: In this retrospective review short- and long-term perspectives have been evaluated for 108 patients who, during 1982 through 1992, had Whipple's operation performed for carcinoma of the pancreatic head (PC, n=63) or the ampullary region (AC, n=45). In 24 patients the operation was not radical (21 with PC and 3 with AC). RESULTS: Total perioperative morbidity was 60%, and 13 patients (12%) died within 30 days of operation. This decreased from 15.2% in the first half of the study period to 8.2% in the second half. Recurrence occurred in 56.2% of the remaining 73 patients, with no significant differences between PC and AC. Recurrence was related to regional lymph node metastases and poor tumour differentiation. Overall 5-year survival was 7.4% for PC and 24.8% for AC. For patients with radically excised tumours surviving 30 days the 5-year survival rates were 13.1% for PC and 30% for AC. CONCLUSION: Careful preoperative evaluation is still of great importance.

Histochemical tracing of zinc ions in the rat testis.

To detect free zinc ions in the rat testes four rats were transcardially perfused with Na2S, and the seminiferous tubules from two other rats were incubated in Na2S. Sections from the two sources were autometallographically (AMG) developed, whereby zinc sulphide crystal lattices created in the tissue by the sulphide treatment were silver enhanced. Light microscopical analysis showed zinc ions in primary spermatogonia until the zygotene primary spermatocytes (stage I), in late pachytene spermatocytes (stages XII and XIII), and in late spermatids from step 15 to step 19 (stages I-VIII). The highest intensity of AMG grains was detected in the residual bodies and tails of step 19 spermatids. Grains were occasionally found in the cytoplasm of Leydig cells. Sections from animals treated with the chelator diethyldithiocarbamate prior to sulphide treatment showed a complete lack of AMG staining. At ultrastructural levels the AMG grains were found in smooth-surfaced endoplasmic reticulum of all spermatogonial stages, and in the acrosome, midpiece, and tail of late spermatids. The presence of zinc ions in preleptotene spermatocytes and cytoplasmic lobes of late spermatids suggests a specific role of free zinc at the onset of meiosis and at spermiation.

Autometallographic demonstration of zinc ions in rat sperm cells.

An in-vitro technique for autometallographic (AMG) demonstration of chelatable zinc in electroejaculated sperm cells and spermatozoa from the epididymis is presented and the localization of zinc ions in rat spermatozoa is described. Sperm cells from caput epididymis showed zinc staining in all parts of the tail and a sparse, dispersed staining in the acrosome. Spermatozoa from cauda epididymis showed heavy staining in the acrosome but no staining in the tail, or post-acrosomal part of the sperm head. This distinct acrosomal AMG staining was also found in ejaculated spermatozoa, but additionally a segmentation of the tail was seen based on differences in staining intensity. The membrane penetrating chelator diethyldithiocarbamate (DEDTC) was found to block the AMG staining whereas calcium-EDTA, known not to pass through cell membranes, did not influence the staining, proving that the detected zinc ions are intracellularly located. Two different approaches for demonstrating the presence of a chelatable zinc pool at electron microscope levels are presented, and the ultrastructural presence of AMG grains located in the acrosome and in the mitochondria of the midpiece is demonstrated. It is postulated that an exchange of zinc ions takes place between the epididymal epithelium and the sperm cells as they pass along the epididymal duct.

Histochemical demonstration of zinc ions in ejaculated human semen.

A revised in-vitro technique for autometallographic demonstration of chelatable zinc in the human ejaculate is presented, and the localization of the loosely bound pool of zinc ions is described in semen smears and at the ultrastructural level. In semen smears, black autometallographic (AMG) grains indicated the presence of zinc ions dispersed between the spermatozoa. These AMG grains have the same size as grains associated with the sperm tail and may have the same origin. EM analysis of AMG-developed smears fixed in osmium suggested that the detected zinc ions might be related to huge protein molecules present in semen and adhering to the surface of the spermatozoa. Spermatozoa in AMG-stained smears exhibited zinc ions in the midpiece and head, and also joined to the membrane of the tail. Washed spermatozoa exhibited zinc ions only within the midpiece. Ultrastructurally, they were found located in the helecine mitochondria. A few grains were found in the acrosome of the washed spermatozoa. Treatment with the chelating agent DEDTC resulted in complete bleaching of the zinc staining. These findings and the fact that calcium EDTA acid blocks the plasma and surface staining, but not the acrosomal and mitochondrial staining, suggest that chelatable zinc ions exist in two separate pools in human semen.

Ultrastructural localization of zinc ions in the rat prostate: an autometallographic study.

BACKGROUND: The prostate contains high amounts of free zinc ions which are excreted into the seminal fluid. The extra- and intracellular distribution of zinc ions using the highly specific autometallographical (AMG) method is described. METHODS: Prostates from sulfide-perfused rats were excised, and the ZnS crystals were silver-enhanced to sizes detectable by the electron and light microscope. RESULTS: AMGZnS grains were found primarily in the acinic lumen of the lateral lobes. The dorsal lobe stained only faintly, while the ventral lobe was void of grains. At ultrastructural levels, the presence of zinc ions was confined to apical secretory vesicles and lysosome-like structure of the epithelium of mainly the lateral lobes. CONCLUSIONS: We suggest a constant secretion of zinc ions from the epithelial cells into both the acinar lumen and the intercellular canaliculi, and that the zinc enriched secretory cells in the prostate belong to a system of glandular cells that uses zinc ions to aggregate macromolecules to be excreted.