Human hepatic stem cells from fetal and postnatal donors

Human hepatic stem cells (hHpSCs), which are pluripotent precursors of hepatoblasts and thence of hepatocytic and biliary epithelia, are located in ductal plates in fetal livers and in Canals of Hering in adult livers. They can be isolated by immunoselection for epithelial cell adhesion molecule-positive (EpCAM+) cells, and they constitute approximately 0.5-2.5% of liver parenchyma of all donor ages. The self-renewal capacity of hHpSCs is indicated by phenotypic stability after expansion for >150 population doublings in a serum-free, defined medium and with a doubling time of approximately 36 h. Survival and proliferation of hHpSCs require paracrine signaling by hepatic stellate cells and/or angioblasts that coisolate with them. The hHpSCs are approximately 9 microm in diameter, express cytokeratins 8, 18, and 19, CD133/1, telomerase, CD44H, claudin 3, and albumin (weakly). They are negative for alpha-fetoprotein (AFP), intercellular adhesion molecule (ICAM) 1, and for markers of adult liver cells (cytochrome P450s), hemopoietic cells (CD45), and mesenchymal cells (vascular endothelial growth factor receptor and desmin). If transferred to STO feeders, hHpSCs give rise to hepatoblasts, which are recognizable by cordlike colony morphology and up-regulation of AFP, P4503A7, and ICAM1. Transplantation of freshly isolated EpCAM+ cells or of hHpSCs expanded in culture into NOD/SCID mice results in mature liver tissue expressing human-specific proteins. The hHpSCs are candidates for liver cell therapies.     

Psychosocial issues need more attention in COPD self-management education

Abstract

Objective: To find out how regularly the contents of patient education regarded as essential for COPD patients’ self-management are provided by healthcare professionals in specialised healthcare (SHC) and primary healthcare (PHC) in Finland.

Design: A cross-sectional study based on an e-questionnaire with 42 items on the content of self-management education of COPD patients.

Setting: The study sample included all public SHC units with pulmonary outpatient clinics (n?=?29) and nine out of 160 health centres in Finland.

Subjects: 83 doctors and 162 nurses.

Main outcome measures: The respondents’ answers on how regularly they included the contents regarded as essential for COPD patients’ self-management in their education of COPD patients.

Results: COPD patients were educated regularly on medical issues regarding COPD treatment, such as smoking cessation, exercise and pharmacological treatment. However, issues vital for coping with the disease, such as psychological well-being, stress management or fatigue, were often ignored. Patient education in SHC seemed to be more systematic than education in PHC. The education provided by the asthma/COPD nurses (n?=?70) was more systematic than the education provided by the other nurses (n?=?84).

Conclusion: Healthcare professionals’ continuous education should cover not only the medical but also the psychosocial aspects of coping with COPD. The role of doctors and nurses should be considered to ensure that there is no gap in COPD patients’ education. Training asthma/COPD nurses and promoting specialised nurse-led asthma/COPD clinics in primary care could be beneficial while improving practices of patient education that enhance patients’ ability to cope with the disease.

• KEY POINTS

• Issues vital for coping with chronic obstructive pulmonary disease (COPD), such as psychological well-being, stress and fatigue, are irregularly included in self-management education both in primary and specialised healthcare.

• Patient education provided by asthma/COPD nurses is more regular than patient education provided by other nurses.

• The distribution of work between doctors and nurses should be considered to ensure that there is no gap in COPD patients’ education.

     

ERP denoising in multichannel EEG data using contrasts between signal and noise subspaces

In this paper, a new method intended for ERP denoising in multichannel EEG data is discussed. The denoising is done by separating ERP/noise subspaces in multidimensional EEG data by a linear transformation and the following dimension reduction by ignoring noise components during inverse transformation. The separation matrix is found based on the assumption that ERP sources are deterministic for all repetitions of the same type of stimulus within the experiment, while the other noise sources do not obey the determinancy property. A detailed derivation of the technique is given together with the analysis of the results of its application to a real high-density EEG data set. The interpretation of the results and the performance of the proposed method under conditions, when the basic assumptions are violated – e.g. the problem is underdetermined – are also discussed.Moreover, we study how the factors of the number of channels and trials used by the method influence the effectiveness of ERP/noise subspaces separation. In addition, we explore also the impact of different data resampling strategies on the performance of the considered algorithm. The results can help in determining the optimal parameters of the equipment/methods used to elicit and reliably estimate ERPs.     

Compensation by reduced L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor responses in a mouse model with reduced gamma-aminobutyric acid type A receptor-mediated synaptic inhibition

L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists increase the threshold for electroshock-induced convulsions. Here, we show that a transgenic mouse line overexpressing cerebellum-restricted gamma-aminobutyric acid type A (GABA(A)) receptor alpha6 subunit in the hippocampal CA1 pyramidal cells (Thy1alpha6 mouse line) exhibits about a 20% increase in the electroshock current intensity inducing tonic hindlimb extension convulsion in 50% of the mice compared with that of their wild-type controls. AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in patch clamp recordings of CA1 pyramidal neurons in hippocampal slices had decreased amplitudes (8.4 +/- 2.2 pA) in the transgenics compared with the wild types (10.3 +/- 2.5 pA) but showed no change in current decay or frequency. Our results suggest that decreased AMPA-mediated neurotransmission might explain the increased threshold for electroconvulsions and warrant further studies on the regulation between various components of inhibition and excitation in neurons.     

Successful weight maintenance preserves lower levels of oxidized LDL achieved by weight reduction in obese men

OBJECTIVE: We studied the association between weight maintenance, oxidized low-density lipoprotein (ox-LDL) and other lipoproteins in obese men. METHODS: A 2-month weight reduction phase (WRP) with a very-low-energy diet was followed by a 6-month weight maintenance period and an unsupervised 2-year follow-up. Ninety men entered and 68 (76%) completed the study. Subjects were analyzed as one group and after division into two subgroups: 20 most successful men in maintaining the lost weight (subgroup 1) and the remaining (n=48) men (subgroup 2). Ox-LDL was measured by quantifying the amount of conjugated dienes in LDL particles. RESULTS: The mean (+/-s.d.) weight reduction at the end of the WRP (n=68) was 14% (confidence interval (CI) 12.9-14.7%, 14.5+/-4.2 kg, P<0.001). Ox-LDL decreased by 22% (CI 16.9-28.1, 12.3+/-15.4 micromol/l, P<0.001). At the end of the 2-year follow-up, the regain in weight from the end of the WRP was 11% (CI 9.0-12.4, 9.6+/-6.2 kg, P<0.001). The regain in ox-LDL was 30% (CI 18.7-41.2, 8.2+/-15.4 micromol/l, P<0.001). In subgroup 1 vs 2, the respective regains were 3% (CI 0.9-4.2, 2.2+/-3.0 kg, P=0.006) vs 14% (CI 12.7-15.6, 12.9+/-4.0 kg, P<0.001) regarding weight and 9% (2.0+/-6.9 micromol/l, P=NS) vs 39% (CI 23.7-53.9, 11.2+/-17.2 micromol/l, P相似文献   

The prevalence of alexithymia and its relationship with Youth Self-Report problem scales among Finnish adolescents

This study investigated the relationship between alexithymia, depressive symptoms, and Youth Self-Report (YSR) self-image profiles among 13 to 18-year-old adolescents (n = 7087) attending school in Kuopio, Finland. The final sample consisted of 3936 adolescents (1801 boys, 2135 girls) who completed structured self-rating questionnaires (Toronto Alexithymia Scale [TAS] 20, Beck Depression Inventory [BDI], and YSR) during class periods at school. The overall prevalence of alexithymia was 7.3%. However, girls in all age groups were more frequently alexithymic than boys. Regardless of sex, alexithymic youths reported more depressive symptoms as well as internalizing and externalizing problems than the others. A YSR total score of more than 70 was recorded among 33.4% of alexithymic compared with 3.7% of nonalexithymic adolescents. The TAS-20 correlated significantly with the BDI score, YSR total score, and with internalizing problems. This study revealed alexithymia among adolescents to be associated with various complications such as depressive symptoms, high scores in YSR problem scales, and difficulties in social relationships. Our findings indicate that these adolescents are at high risk of mental disorders and require treatment interventions.     

Parallel input makes the brain run faster

In serial sensory processing, information flows from the thalamus via primary sensory cortices to higher-order association areas. However, association cortices also receive, albeit weak, direct thalamocortical sensory inputs of unknown function. For example, while information proceeds from primary (SI) to secondary (SII) somatosensory cortex in a serial fashion, both areas are known to receive direct thalamocortical sensory input. The present study examines the potential roles of such parallel input arrangements. The subjects were presented with median nerve somatosensory stimuli with the instruction to respond with the contralateral hand. The locations and time courses of the activated brain areas were first identified with magnetoencephalography (MEG). In a subsequent session, these brain areas were modulated with single-pulse transcranial magnetic stimulation (TMS) at 15-210 ms after the somatosensory stimulus while electroencephalography (EEG) was recorded. TMS pulses at 15-40 ms post-stimulus significantly speeded up reaction times and somatosensory-evoked responses, with largest facilitatory effects when the TMS pulse was given to contralateral SII at about 20 ms. To explain the results, we propose that the early somatosensory-evoked physiological SII activation exerts an SII-->SI influence that facilitates the reciprocal SI-->SII pathway - with TMS to SII we apparently amplified this mechanism. The results suggest that the human brain may utilize parallel inputs to facilitate long-distance cortico-cortical connections, resulting in accelerated processing and speeded reaction times. This arrangement could also allow very early top-down modulation of the bottom-up stream of sensory information.