Aberrant frontostriatal connectivity in Alzheimer's disease with positive palmomental reflex.

BACKGROUND AND PURPOSE: Primitive reflexes may reoccur in various neurodegenerative diseases. However, little is known about their structural and functional correlates in the human brain. Notably, the neural mechanisms underlying a positive palmomental reflex (PMR) are poorly understood. As recent studies link Alzheimer's disease (AD)-related primitive reflexes to a dysfunction of the corticostriatal motor circuit (CMC), we conducted the present study to investigate functional and structural correlates of a positive PMR. We hypothesized an involvement of frontostriatal structures and an impairment of the CMC. METHODS: Using whole-brain resting-state functional connectivity (FC), hypothesis and FC result-based probabilistic tractography, and voxel-based morphometry analyses, we compared two groups of AD patients with either positive (n = 12) or negative PMR (n = 12). RESULTS: No significant differences in grey matter volume or structural connectivity (SC) could be observed between the PMR-positive and PMR-negative groups. In contrast, the PMR-positive group showed a decreased seed-to-voxel FC between the bilateral supplementary motor area and parts of the right-hemispherical caudate nucleus and thalamus and a decreased region of interest (ROI)-to-ROI FC between the left putamen and the left superior frontal gyrus. CONCLUSION: Data suggest that dysfunction of the CMC reflected by decreased FC underlies a positive PMR in patients with AD. The lack of significant grey matter or SC differences might reflect that changes in FC appear before changes in SC in the structures of the CMC and brain atrophy.

Surgical technique for placement of the automated low flow ascites pump (Alfapump).

Approximately 10% of patients with ascites associated with cirrhosis fail to respond to dietary rules and diuretic treatment and therefore present with refractory ascites. In order to avoid iterative large-volume paracentesis in patients with contraindication to TIPS, the automated low flow ascites pump system (Alfapump) was developed to pump ascites from the peritoneal cavity into the urinary bladder, where it is eliminated spontaneously by normal micturition. This manuscript reports the surgical technique for placement of the Alfapump.

[Biliary atresia and congenital cholestatic syndromes : Characteristics before, after and during transition]. / Gallengangatresie und angeborene Cholestasesyndrome : Besonderheiten vor, nach und während der Transition.

BACKGROUND: A growing number of patients with biliary atresia and congenital cholestatic syndromes are reaching adulthood. These patients often have a number of typical medical features, including specific characteristics of liver transplantation medicine. OBJECTIVE: What are the special features in the care of adults suffering from liver diseases with manifestation in childhood and adolescence, both before and after liver transplantation (LTX). How does the progression of individual diseases differ depending on age at manifestation? What are specific aspects following pediatric LTX? PATIENTS AND METHODS: Evaluation and discussion of existing guidelines and recommendations of the individual disciplines and professional societies as well as the current literature. Joint discussion of the recommendations between disciplines (gastroenterology, pediatric gastroenterology, surgery). Inclusion of center-specific experiences with transition from existing transition outpatient departments and training. RESULTS: The recommendations are presented specifically for each disease. Special features in individual diseases after LTX are also discussed. Diagnosis-independent general treatment concepts for cholestasis and chronic liver disease are presented. CONCLUSION: Patients with biliary atresia and congenital cholestatic syndromes have a life-long chronic liver disease with and without LTX and require specific medical care. The patients benefit from the pooling of expertise in the individual disciplines.

[Transplant Surgeon Meets Nephrologist: Important Nephrological Aspects Before and After Kidney or Liver Transplantation]. / Abdominalchirurgie trifft Nephrologie: Wichtige nephrologische Aspekte vor und nach Nieren- bzw. Lebertransplantation.

In cases of chronic renal insufficiency, successful kidney transplantation is the method of choice to restore patients' health, well-being and physical fitness. The interdisciplinary collaboration of nephrologists and transplant surgeons has always been a prerequisite for the successful pre-, peri- and post-transplant care of renal transplant patients. The same holds true for liver transplant patients. Here the nephrologist is often involved in cases requiring pre- or post-transplant dialysis as well as in decision making for combined liver-kidney transplantation. This review focuses on nephrological aspects in patient care before and after kidney and liver transplantation.

ω-Transaminases for the amination of functionalised cyclic ketones.

The potential of a number of enantiocomplementary ω-transaminases (ω-TAms) in the amination of cyclic ketones has been investigated. After a preliminary screening of several compounds with increasing complexity, different approaches to shift the equilibrium of the reaction to the amine products were studied, and reaction conditions (temperature and pH) optimised. Interestingly, 2-propylamine as an amine donor was tolerated by all five selected ω-TAms, and therefore used in further experiments. Due to the higher conversions observed and interest in chiral amines studies then focused on the amination of α-tetralone and 2-methylcyclohexanone. Both ketones were aminated to give the corresponding amine with at least one of the employed enzymes. Moreover, the amination of 2-methylcyclohexanone was investigated in more detail due to the different stereoselectivities observed with TAms used. The highest yields and stereoselectivities were obtained using the ω-TAm from Chromobacterium violaceum (CV-TAm), producing 2-methylcyclohexylamine with complete stereoselectivity at the (1S)-amine position and up to 24 : 1 selectivity for the cis : trans [(1S,2R) : (1S,2S)] isomer.

Everolimus and early calcineurin inhibitor withdrawal: 3-year results from a randomized trial in liver transplantation.

The feasibility of de novo everolimus without calcineurin inhibitor (CNI) therapy following liver transplantation was assessed in a multicenter, prospective, open-label trial. Liver transplant patients were randomized at 4 weeks to start everolimus and discontinue CNI, or continue their current CNI-based regimen. The primary endpoint was adjusted estimated GFR (eGFR; Cockcroft-Gault) at month 11 post randomization. A 24-month extension phase followed 81/114 (71.1%) of eligible patients to month 35 post randomization. The adjusted mean eGFR benefit from randomization to month 35 was 10.1 mL/min (95% confidence interval [CI] -1.3, 21.5 mL/min, p = 0.082) in favor of CNI-free versus CNI using Cockcroft-Gault, 9.4 mL/min/1.73 m(2) (95% CI -0.4, 18.9, p = 0.053) with Modification of Diet in Renal Disease (four-variable) and 9.5 mL/min/1.73 m(2) (95% CI -1.1, 17.9, p = 0.028) using Nankivell. The difference in favor of the CNI-free regimen increased gradually over time due to a small progressive decline in eGFR in the CNI cohort despite a reduction in CNI exposure. Biopsy-proven acute rejection, graft loss and death were similar between groups. Adverse events led to study drug discontinuation in five CNI-free patients and five CNI patients (12.2% vs. 12.5%, p = 1.000) during the extension phase. Everolimus-based CNI-free immunosuppression is feasible following liver transplantation and patients benefit from sustained preservation of renal function versus patients on CNI for at least 3 years.

[Sleep disturbances and suicidality: relationships and clinical implications]. / Schlafstörungen und Suizidalität: Zusammenhänge und klinische Bedeutung.

Besides several risk factors for suicide, there is a recent increase in clinical and epidemiological studies pointing to a potential relationship between sleep loss or sleep disturbances and suicidality. This work, based on a systematic literature research, gives an overview on the findings of relationships between suicidality (i. e., suicidal thoughts, suicide attempts, suicides) and sleep disturbances, especially insomnia, nightmares, but also hypersomnia and nocturnal panic attacks. There is evidence that sleep disturbances in suicidal insomniacs with comorbid psychiatric disorder are independently predictive for suicidality, too. Shared aspects of pathogenesis of the two entities and therapeutic options are also discussed. Recognition of sleep disturbances is essential for suicide prevention in clinical practice.

Metabolic syndrome: a follow-up study of acute depressive inpatients.

Previous studies pointed out the high prevalence of the metabolic syndrome among patients with bipolar disorder and major depression. A link between depression and a metabolic syndrome remains in dispute despite these studies. This study was conducted to evaluate the occurrence of the metabolic syndrome in depressive inpatients, to analyze the association between the severity of depression and the metabolic syndrome and to screen specific laboratory values in the course of depressive illness. 60 acute depressive patients were recruited for the study and underwent psychometric testing [21-item Hamilton Depression Rating Scale (HAMD), Beck Depression Inventory (BDI), Clinical Global Impression Scale (CGI) and Global Assessment of Functioning Scale (GAF)] and a metabolic syndrome screening using the modified criteria of the American National Cholesterol Education Program (NCEP) Treatment Panel III (ATP III). Moreover, CRP, cholesterol, HDL-cholesterol, fasting glucose, triglyceride and leptin levels were measured. 42 patients were reexamined in state of (partial) remission. Depression was reassessed using the 21-item HAMD, and laboratory values were analyzed a second time. 25% of the depressive patients fulfilled the criteria of metabolic syndrome (MS+). Only in the MS+ group, a positive correlation between triglyceride blood levels and severity of depression became evident as well in the state of acute depression as in the state of remission. In the group of patients without metabolic syndrome, laboratory values were not associated with severity of depression. An association between metabolic parameters and the course of depression could only be detected in the group of patients with metabolic syndrome. These findings suggest that, in these patients, a beneficial outcome of depressive illness may improve the metabolic situation.

Design of super-strong and thermally stable nanotwinned Al alloys via solute synergy.

Al alloys have widespread industrial applications. However, their mechanical strength is often much lower than steels. Here, we investigate the influence of solutes on achieving ultrahigh strength and thermal stability of nanotwinned Al alloys. In situ micropillar compression tests show the addition of a small amount of Ti can significantly increase the mechanical strength of Al-Ni alloys to 2 GPa. Deformation induced detwinning, Ni segregation and grain coarsening as discovered in binary Al-Ni alloys are mostly absent in the ternary Al-Ni-Ti alloys. Moreover, the ternary Al-Ni-Ti alloys have outstanding thermal stability. Density function theory calculations reveal the synergetic pinning effect of Ni-Ti solute pairs on incoherent twin boundaries. This study demonstrates that the proper selection of synergistic solute pairs is critical to improve the thermal stability and mechanical properties of nanotwinned Al alloys.

Single-trial P3 amplitude and latency informed event-related fMRI models yield different BOLD response patterns to a target detection task.

Using single-trial parameters as a regressor in the General Linear Model (GLM) is becoming an increasingly popular method for informing fMRI analysis. However, the parameter used to characterise or to differentiate brain regions involved in the response to a particular task varies across studies (e.g. ERP amplitude, ERP latency, reaction time). Furthermore, the way in which the single-trial information is used in the fMRI analysis is also important. For example, the single-trial parameters can be used as regressors in the GLM or to modify the duration of the events modelled in the GLM. The aim of this study was to investigate the BOLD response to a target detection task when including P3 amplitude, P3 latency and reaction time parameters in the GLM. Simultaneous EEG-fMRI was recorded from fifteen subjects in response to a visual choice reaction time task. Including P3 amplitude as a regressor in the GLM yielded activation in left central opercular cortex, left postcentral gyrus, left insula, left middle frontal gyrus, left insula and left parietal operculum. Using P3 latency and reaction time as an additional regressor yielded no additional activation in comparison with the conventional fMRI analysis. However, when P3 latency or reaction time was used to determine the duration of events at a single-trial level, additional activation was observed in the left postcentral gyrus, left precentral gyrus, anterior cingulate cortex and supramarginal gyrus. Our findings suggest that ERP amplitudes and latencies can yield different activation patterns when used to modify relevant aspects of the GLM.

Expression of CD4 on Epstein-Barr virus-immortalized B cells.

Human antigen presenting cells commonly express CD4 but the significance of this phenomenon has not been clarified. We analyzed a panel of Epstein-Barr virus-immortalized B cells (so called lymphoblastoid cell lines, LCL) by using flow cytometry, DNA-microarray analysis, and reverse transcriptase-polymerase chain reaction (RT-PCR). The number of CD4(+) cells varied from cell line to cell line but expression of CD4 was detected by flow cytometry and RT-PCR in all investigated cell lines. To characterize CD4 expressing LCL in more detail, we separated CD4(+) and CD4(-) cells from single cell lines by using immunomagnetic beads. When we cultured sorted CD4(+) and CD4(-) cells, we observed that CD4 expression was stable for several passages. However, the number of CD4(+) cells decreased with time in culture. We never observed that CD4(-) cell lines returned back to a CD4(+) phenotype. DNA-microarray analysis of isolated CD4(+) and CD4(-) cells indicated that the overall gene expression profile of both cell populations was highly similar. In addition, CD4(+) and CD4(-) cells showed the same allostimulatory capacity. CD4(+) LCL showed a slightly increased interleukin-16 induced chemotaxis. Differences in the gene expression profile of CD4(+) and CD4(-) cell lines suggested that loss of CD4 expression occurred during a differentiation step involving achaete-scute complex homolog-like 1.

[Current problems of kidney transplantation]. / Aktuelle Probleme der Nierentransplantation.

The long-term problems after kidney transplantation have changed considerably in recent years. While formerly immunosuppression and prevention of acute rejection were of prime concern, now attention focuses on chronic alterations of the transplanted organ and long-term survival of the patients. The transplantation procedure itself has evolved into a standardized technique with a high level of surgical quality. Problems involving organ preservation and ischemia/reperfusion damage also play a role, especially in view of chronic aspects. Monitoring of long-term complications should follow a program for the transplanted organ as well as a program for the patient. Monitoring kidney function should address the organ more precisely than has previously been the case. Serum creatinine level and proteinuria alone provide insufficient information and only change long after cellular deterioration has begun. Hence it is imperative that new testing methods be developed. One possibility is offered by protocol biopsies that allow histological and molecular analysis of the kidney at regular intervals. The patient programs concentrate on diagnostics and treatment of the cardiovascular diseases. Furthermore, the patients must be screened for occurrence of neoplasia. There are no prospective studies covering all cardiovascular risk factors after kidney transplantation. This pertains particularly to the subject of hypertension.

Test-retest variability of resting-state networks in healthy aging and prodromal Alzheimer's disease.

In recent years, changes in resting-state networks (RSN), identified by functional magnetic resonance imaging (fMRI), have gained increasing attention as potential biomarkers and trackers of neurological disorders such as Alzheimer's disease (AD). Intersession reliability of RSN is fundamental to this approach. In this study, we investigated the test-retest reliability of three memory related RSN (i.e., the default mode, salience, and executive control network) in 15 young, 15 healthy seniors (HS), and 15 subjects affected by mild cognitive impairment (MCI) with positive biomarkers suggestive of incipient AD (6 females each). FMRI was conducted on three separate occasions. Independent Component Analysis decomposed the resting-state data into RSNs. Comparisons of variation in functional connectivity between groups were made applying different thresholds in an explorative approach. Intersession test-retest reliability was evaluated by intraclass correlation coefficient (ICC) comparisons. To assess the effect of gray matter volume loss, motion, cerebrospinal fluid based biomarkers and the time gap between sessions on intersession variation, the former four were correlated separately with the latter. Data showed that i) young subjects ICCs (relative to HS/MCI-subjects) had higher intersession reliability, ii) stringent statistical thresholds need to be applied to prevent false-positives, iii) both HS and MCI-subjects (relative to young) showed significantly more clusters of intersession variation in all three RSN, iv) while intersession variation was highly correlated with head motion, it was also correlated with biomarkers (especially phospho-tau), the time gap between sessions and local GMV. Results indicate that time gaps between sessions should be kept constant and that head motion must be taken into account when using RSN to assess aging and neurodegeneration. In patients with prodromal AD, re-test reliability may be increased by accouting for overall disease burden by including biomarkers of neuronal injury (especially phospho-tau) in statistical analyses. Local atrophy however, does not seem to play a major role in regards to reliability, but should be used as covariate depending on the research question.

Geometrical control of pure spin current induced domain wall depinning.

We investigate the pure spin-current assisted depinning of magnetic domain walls in half ring based Py/Al lateral spin valve structures. Our optimized geometry incorporating a patterned notch in the detector electrode, directly below the Al spin conduit, provides a tailored pinning potential for a transverse domain wall and allows for a precise control over the magnetization configuration and as a result the domain wall pinning. Due to the patterned notch, we are able to study the depinning field as a function of the applied external field for certain applied current densities and observe a clear asymmetry for the two opposite field directions. Micromagnetic simulations show that this can be explained by the asymmetry of the pinning potential. By direct comparison of the calculated efficiencies for different external field and spin current directions, we are able to disentangle the different contributions from the spin transfer torque, Joule heating and the Oersted field. The observed high efficiency of the pure spin current induced spin transfer torque allows for a complete depinning of the domain wall at zero external field for a charge current density of [Formula: see text] A m-2, which is attributed to the optimal control of the position of the domain wall.

Antihypertensive effect of 0.1-Hz blood pressure oscillations to the kidney.

BACKGROUND: Physiological blood pressure (BP) fluctuations with frequencies >0.1 Hz can override renal blood flow autoregulation. The influence of such immediate changes in renal perfusion pressure (RPP) on daily BP regulation, eg, via shear stress-stimulated liberation of renal endothelial NO, however, is unknown. Thus, we studied the effects of such RPP oscillations on renal function and on systemic BP during the onset of renal hypertension. METHODS AND RESULTS: Seven beagles (randomly assigned to each of the following protocols) were chronically instrumented for the measurement of systemic BP, RPP, and renal excretory function. An inflatable cuff was used to reduce and to oscillate RPP over 24 hours in the freely moving dog. Reducing RPP to 87+/-2 mm Hg diminished excretion of sodium and water and doubled plasma renin activity (PRA, n=7, P<0. 01) but had no significant effect on urinary nitrate excretion (n=6), a marker of NO generation. Superimposing 0.1-Hz oscillations (+/-10 mm Hg) onto the reduced RPP blunted hypertension, returned fluid excretion almost to control levels, and doubled renal sodium elimination. Nitrate excretion peaked at 8 hours, only to return to control values shortly thereafter. PRA, conversely, was significantly reduced during the last third of the experimental protocols. CONCLUSIONS: BP fluctuations transiently stimulate NO liberation and induce a reduction in PRA, which enhances 24-hour sodium and water excretion and markedly attenuates the acute development of renovascular hypertension.

Persistence of donor lymphocytes in liver allograft recipients.

Occasional cases of graft-versus-host disease after liver transplantation indicate a transfer of donor lymphocytes by human liver grafts. However, little is known about the usual fate and potential function of passenger lymphocytes in clinical liver transplantation. In this study, we have analyzed liver graft recipients for the presence of donor lymphocytes in the early course after transplantation. The presence of such cells in blood, the graft, and, occasionally, the skin was studied by the use of mAb to polymorphic HLA class I determinants and double-staining techniques in flow cytometry and immunocytology. The findings were compared with the clinical courses and with the results of routine graft biopsies. Within the first week after transplantation, in all 16 patients, between 1% and 24% donor lymphocytes (T, NK, and B cells) were detectable in blood, and in 14 of 22 patients (64%), between 2% and 23% donor T cells were found in the graft. After more than 2 weeks, donor cells were still present in blood in 2 of 14 patients at very low numbers. The presence of donor lymphocytes in the graft was associated with intragraft immune activation in 5 of 15 patients, but no clinical rejection occurred in these cases; mild graft-versus-host disease was observed in one patient. These findings demonstrate that donor lymphocytes regularly persist in liver-grafted patients for some time; this transient mixed lymphoid chimerism is only rarely associated with clinical graft-versus-host disease and some evidence even suggests that these donor-derived lymphocytes may exert beneficial immunomodulatory properties.

Distinct expression of cell-cell and cell-matrix adhesion molecules on endothelial cells in human heart and lung transplants.

BACKGROUND AND METHODS: Intercellular reactions and cell-matrix interactions are mediated by a number of specific adhesion molecules. For the intravascular reactivity of leukocytes and thrombocytes the endothelial expression of adhesion ligand molecules is of main importance. This condition may be of special relevance for the organ-specific manifestation of immune reactions in heart and lung transplants. The question was investigated as to whether organ-specific differences exist on arterial, venous, and capillary endothelial lining cells in heart and lung transplants and whether this condition is modified during transplant rejection. Transplant biopsy specimens of 24 heart transplant recipients (n = 303) and lung transplant recipients who underwent retransplantation for rejection (n = 4), as well as normal heart (n = 7) and lung tissue (n = 4), were studied. Cell-cell adhesion molecules (intercellular adhesion molecule-1 (CD54) and -2; LFA-3; CD31; vascular cellular adhesion molecule-1; neural cellular adhesion molecule; E-/P-selectin; CD44) and cell-matrix adhesion molecules (very late antigen-1 through -6; CD51) were studied on cryostat sections by means of standard immunohistology. RESULTS: (1) Arterial, venous, and capilary endothelia in lung and heart tissue show a distinct pattern of cell-cell and cell-matrix adhesion molecules: capillary and venous endothelia are in contrast to arterioles negative for vascular cellular adhesion molecule-1 and P-selectin. Arterial endothelia of the lung, in contrast to veins and capillaries, express no receptors for laminin (very late antigen-2 and very late antigen-6). (2) With transplant rejection, an induction of a number of adhesion molecules was noted on all endothelial lining cells in heart and lung transplants (intercellular adhesion molecule-1[CD54], intercellular adhesion molecule-2, lymphocyte function antigen-3, very late antigen-2, and very late antigen-6). Capillaries of the lung, in contrast to heart capillaries, displayed no inducibility of vascular cellular adhesion molecule-1 and E-selectin. In heart transplants, differences between capillaries and arteriovenous endothelia were found for virus-like agent-2 and -3. CONCLUSIONS: These results show a distinct expression of a both cell-cell and cell-matrix adhesion molecules on arterial, venous, and capillary endothelia of heart and lung transplants. This expression may influence the local regulation of leukocyte and thrombocyte adhesion during transplant rejection. Especially lung capillaries show a lack of inducibility for vascular cellular adhesion molecule-1 and E- and P-selectin required for the induction phase of leukocyte adhesion. This lack was not found in heart transplants. This observation may explain differences in intravascular adhesion and infiltration between vessel compartments in hearts and lungs and could be of relevance for therapeutic interventions to modify leukocyte and thrombocyte adhesion, as during transplant rejection and reperfusion damage.

Allogeneic lymphocyte chimerism after clinical lung transplantation.

Donor lungs contain large amounts of passenger leukocytes which are transferred to the recipient by organ transplantation. In this study we have analysed the fate of these cells and have studied the populations of donor leucocytes detectable in the blood circulation of ten lung transplanted patients during the first postoperative weeks. To this aim we have applied immunocytological as well as flow cytometric analyses using monoclonal antibodies against polymorphic HLA class I antigens that differed between donor and recipient as well as antibodies against cell differentiation markers. The results demonstrate that donor cells can be detected in the circulation of all lung transplanted patients but there is a considerable interindividual variability between 0.9% and 17.5% (mean 5.1%) on postoperative day 3. Cells were usually detectable for 2-4 weeks and had disappeared in all patients after 1 month. The circulating donor cells consisted exclusively of lymphocytes. T cells were the predominant population, most of which seemed to be CD45R0+, but B and NK (natural killer) cells were also present. Probably due to the small numbers of patients studied no correlation between clinical parameters and the extent of donor lymphocyte persistence; there were no clinical graft-versus-host reactions. The findings demonstrate the regular existence of a transient (macro)chimerism due to passenger lymphocytes in the early phase after lung transplantation. The immunological function and the relation between this phenomenon and the long-term microchimerism which frequently develops after solid organ transplantation remain unclear.

The efficacy of relaxation training with children.

This paper reviews studies that have examined the efficacy of relaxation training techniques in the treatment of childhood disorders. Methodological problems encountered in doing research in this area resemble those found in working with an adult population: imprecise definitions of subject populations and use of a variety of dependent variables from one study to another. Findings suggest that relaxation training is at least as effective as other treatment approaches for a variety of learning, behavioral, and physiological disorders when it is continued over an extended period of time and is augmented by other supportive measures. Needs for future research include better follow-up studies and further investigations with a behaviorally disruptive population.

Guilt, isolation and hopelessness among female survivors of childhood sexual abuse: effectiveness of group work intervention.

OBJECTIVE: This study explores the effects of group work intervention on female survivors' senses of guiltlessness, affiliation and hopefulness. METHOD: Secondary comparative analyses of a large quasi-experiment-based clinical data base were accomplished (Richter, Snider, & Gorey): group work intervention (N = 78) and a waiting-list condition (N = 80). RESULTS: Group work was found to have beneficial effects on adult female survivors' appropriate sense of guiltlessness for their childhood sexual abuse, as well as on their sense of affiliation and hopefulness. Consistent across the three outcome measures of guilt/guiltlessness, isolation/affiliation and hopelessness/hopefulness, 16 to 18 of every 20 such women who participated in group work did better than the average woman in the waiting-list comparison group. Moreover, these apparent clinical benefits were maintained for 6 months (all p < .01). CONCLUSION: Such effects may be characterized as very large, and are generally larger than those previously observed in this field of practice that have typically been based on more general measures of depression, self-esteem or global symptoms.