Identification and characterization of intestinal Peyer's patch interferon-alpha producing (plasmacytoid) dendritic cells

Recently, a subset of murine dendritic cells (DC) has been identified that resembles human plasmacytoid (pDC) the principal interferon-alpha (IFN-alpha) producing cells in blood. In this study, C57BL/10 (B10;H2b) mice were treated with fms-like tyrosine 3 kinase Ligand (Flt3L; 10 microg/d; i.p.; 10 days) that expands DC selectively in vivo. Putative pDC (CD11c+B220+) were identified in the subepithelial dome and in interfollicular regions of intestinal Peyer's patches (PP) from both normal and Flt3L-treated animals. Freshly-isolated, immunobead-purified CD11c+ DC from PP were flow-sorted to obtain lineage- (CD11b-CD19-) CD11c+ B220+ DC (purity>96%). Flow cytometric analysis revealed that these sorted PPpDC were negative for surface markers associated with myeloid DC (CD11b) and expressed only low levels of the "lymphoid-related" DC marker CD8alphaalpha+. They expressed low levels of costimulatory molecules and moderate MHC class II. They proved weak stimulators of na?ve allogeneic (C3H; H2k) T-cell proliferation. Cytospin preparations of sorted CD11c+B220+ cells revealed plasmacytoid morphology similar to that of human pDC. Immunocytochemistry and enzyme immunoassay revealed that, within 24-hour culture with Herpes simplex virus (10 p.f.u./cell), a subpopulation of stimulated (but not unstimulated) CD11c+B220+ DC produced and secreted IFN-alpha. This novel DC subset may play important roles in innate and adaptive immune responses of the gut and in the regulation of mucosal immune reactions.     

Comparison of histological and biochemical hepatic iron indexes in the diagnosis of genetic haemochromatosis.

AIMS: To compare a histological hepatic iron index with a biochemical hepatic iron index, derived from atomic absorption spectroscopy measurements of hepatic iron content, for the diagnosis of genetic haemochromatosis (GH). METHODS: Histological sections of liver biopsy specimens from 70 subjects, who had previously had their biochemical hepatic iron index measured, were examined. The iron stores were scored to derive a histological hepatic iron index and were also graded from 0 to 4 by a standard grading system. The case history of each patient was then reviewed to establish a definitive clinical diagnosis and patients were classified as GH, non-GH or indeterminate. RESULTS: There were 26 cases of GH, 40 cases of non-GH and four indeterminate cases in whom a definite clinical diagnosis was not established. Using a biochemical hepatic iron index cut off level of 2.0, two cases were misclassified, with one case of GH having a biochemical hepatic iron index of 1.8 and one non-GH case having a biochemical hepatic iron index of 3.1. This could not have been improved by altering the cut off level. Using the recommended cut off level of 0.15, the histological hepatic iron index was raised in all cases of GH, but was also increased in 11 of the 40 non-GH patients. The specificity of this histological index can be improved by increasing the cut off level to 0.30. A histological iron grade of > or = 3 is more specific than the histological index but has a lower sensitivity, which particularly affects the diagnosis of younger patients with GH. CONCLUSIONS: The biochemical hepatic iron index is a reliable method for establishing a diagnosis of homozygous GH. In contrast, the histological hepatic iron index as originally described is non-specific and does not reliably distinguish patients with GH from others with a raised hepatic iron index due to other causes. The specificity of this index can be improved by increasing the cut off level used, but the discrimination provided by the histological index is still inferior to that provided by the biochemical hepatic iron index.     

Attachment states of mind, mentalization, and their correlates in a first-episode psychosis sample

Objectives.?Although there has been increased interest in applying attachment theory to the psychological understanding of psychosis, research to date has focused on self-reported attachment and psychotic symptomatology. This study presents evidence for applying attachment and mentalization constructs to understanding engagement and adaptation to first-episode psychosis (FEP), using a narrative based interview. Design.?A cross-sectional cohort design was used. Methods.?Thirty-four individuals with a first episode of psychosis were interviewed using the Adult Attachment Interview. Attachment classifications and reflective function scores were derived from the interview. Psychotic symptomatology, premorbid adjustment, duration of untreated psychosis, and psychological variables were also measured. Results.?Attachment distribution was heterogeneous in the sample, although the majority of participants were classified dismissing of attachment. Mentalization scores were consistent with previous clinical samples. Attachment and mentalization were unrelated to psychotic symptomatology. Conclusions.?The current study demonstrates, albeit with a small clinical sample, the importance of assessing attachment and mentalization via narrative methods. The findings also have clinical implications for understanding the process of engagement and adaptation in FEP.     

Corrective Experiences of Psychotherapists in Training

Although the concept of corrective experiences (CEs) is usually linked to the process of change in psychotherapy patients, we investigated them in the professional development of therapists‐in‐training. Inasmuch as psychotherapy is a relational process, it is important to look closely at how therapists reach the position of a competent partner in corrective experiencing. In this study, we interviewed 10 therapists‐in‐training undergoing their own training therapy. Responses to these semistructured interviews were analyzed using a computer‐assisted grounded theory method. The 499 first‐level categories were grouped into 5 main themes: therapist characteristics, therapist technical interventions, therapist relational interventions, relationship experience, and outcome experience. Two core categories representing corrective experiencing were (a) unexpected unconditional support from and trust in their own therapist and (b) unexpected confrontation and limitation with their therapist as well as awareness of self–other boundaries. Results are discussed in the broader context of the CE literature, relational theory, and relational practice.     

Health-related quality of life,uncertainty and coping strategies in solid organ transplant recipients during shielding for the COVID-19 pandemic

Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID-19. Our objective was to investigate health-related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID-19 pandemic. A cross-sectional survey of adult SOT recipients undergoing follow-up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ-5D-5L, Short-form Mishel Uncertainty in Illness Scale (SF-MUIS) and Brief Cope, respectively. Interactions with COVID-19 risk perception, access to health care, demographic and clinical variables were assessed. The survey was completed by 826 of 3839 (21.5%) invited participants. Overall, low levels of uncertainty in illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self-perceived susceptibility to COVID-19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to health care, a perceived high risk of severe COVID-19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies was associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.     

Immunologic status of hemophilia patients treated with cryoprecipitate or lyophilized concentrate

We evaluated 37 patients with moderate or severe hemophilia A and six patients with severe factor IX deficiency for clinical or laboratory evidence of immune abnormalities. Patients were assigned to one of four groups according to the type of clotting factor replacement. Twenty patients had received only cryoprecipitate during the two years preceding the evaluation (group I); 11 additional patients were treated predominantly with cryoprecipitate but had also received up to nine bottles of factor VIII concentrate (group II); six patients received factor VIII concentrate (group III); six patients received factor IX concentrate (group IV). There was no clinical or laboratory evidence of immunodeficiency among the 43 patients. The mean absolute number of Th cells was normal in all patient groups, but the mean absolute number of Ts cells was increased compared with controls, both in patients treated with cryoprecipitate and in patients treated with factor VIII or factor IX concentrate. There was no correlation between the Th/Ts ratio and patient age, alanine aminotransferase level, hepatitis serology, in vitro lymphocyte function, or amount of clotting factor administered. Our observations demonstrate that the volunteer or commercial origin of clotting factor replacement cannot fully explain the alterations in lymphocyte subset distribution previously described in patients with hemophilia A.     

Evidence for heterogeneity in hereditary hemochromatosis: Evaluation of 174 persons in nine families

Hereditary hemochromatosis is an autosomal recessive disease in which the gene is linked to the HLA system. Investigation of nine unrelated probands and their family members has revealed distinct groups based on biochemical and clinical manifestations of the disease. Four different types of disease expression were identified: Group I—classic hereditary hemochromatosis with elevated transferrin saturation, serum ferritin levels, and liver iron content; Group II—severe iron overload, accelerated disease manifesting at an early age; Group III—elevated total body iron stores, normal transferrin saturation and serum ferritin levels; Group IV—markedly elevated findings on serum biochemical tests, e.g., transferrin saturation, serum ferritin levels, with minimal elevation in total body iron stores. This evidence for several clearly distinguishable modes of expression in different families suggests that more than one genetic lesion in iron metabolism may be responsible for iron overload in hereditary hemochromatosis. This genetic heterogeneity may be helpful in delineating the fundamental abnormalities in iron metabolism in this group of disorders.     

Researching the impact of oral health on diet and nutritional status: Methodological issues

Objectives

Assessment of the impact of dental function on diet and nutritional status requires robust methodologies and a standardised approach to increase accuracy of results and to facilitate cross study comparisons. The objectives of this paper are: to report the outcomes of a consensus workshop that critically reviewed publications reporting on dietary methodologies in relation to the impact of oral health on nutrition; to highlight future directions for research and; to make recommendations for appropriate use of methodologies for future research.

Data

Data relevant to nutrition and dental status published from 1980 to 2005 in English were presented at the consensus workshop for discussion and appraisal.

Sources

Relevant papers were retrieved through PubMed. Relevant texts were obtained from the library at Newcastle University, UK.

Study selection

A purposive sample of original articles that illustrated the application of a range of nutritional methodologies to the study of oral health impacts was identified. Original flagship texts on nutritional methodologies were reviewed.

Conclusions

Numerous studies have shown an association between loss of teeth and inferior diet. Further research is required to elucidate the impact of novel approaches to prosthetic rehabilitation and the impact of contemporaneous dietary and dental intervention on diet, nutritional status, disease progression and quality of life.The recommendation of the consensus workshop was that future studies should adopt a comprehensive approach to the assessment of nutrition that encompasses measurement of diet, body composition, biochemical indices of intake and levels of nutrients, and functional biomarkers of disease.