The prevalence and clinical relevance of hyperhomocysteinemia suggesting vitamin B12 deficiency in presumed healthy infants

Background Previous studies have demonstrated a high prevalence of biochemical vitamin B12 deficiency in infants in Norway. Increased total homocysteine (tHcy) is the most important marker of B12 deficiency in infants. There is a need to evaluate its clinical relevance. Aims To investigate the prevalence of hyperhomocysteinemia (S-tHcy > 8 μmol/L) suggestive of suboptimal B12 status and the prevalence of clinically relevant hyperhomocysteinemia in presumed healthy infants in Norway. Further, to evaluate risk factors, presence of symptoms and psychomotor development in these children. Methods In a prospective study we clinically examined 252 infants aged 3–7 months using standardized neurological and psychomotor tests prior to analyzing biochemical B12 deficiency markers in 250 infants. Results Twenty-five of 250 (10%) infants had hyperhomocysteinemia combined with clinically relevant symptoms suggestive of B12 deficiency. Hyperhomocysteinemia was associated with tremor, excessive sleep, and sub-normal scores in the fine motor section of the Ages and Stages Questionnaire. One-hundred and fourteen of 250 (46%) infants had hyperhomocysteinemia. Multiple regression analysis showed months of infant formula use as the strongest negative predictor for hyperhomocysteinemia. Conclusion We have demonstrated associations between symptoms suggestive of infant B12 deficiency and increased levels of tHcy in presumed healthy infants The combination of hyperhomocysteinemia and associated relevant symptoms suggestive of B12 deficiency was a common finding, albeit most infants with hyperhomocysteinemia did not show symptoms.publishedVersio

Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders (“conditions”) then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40–50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together

Rasch analysis of the Psychiatric Out-Patient Experiences Questionnaire (POPEQ)

<p>Abstract</p> <p>Background</p> <p>The Psychiatric Out-Patient Experiences Questionnaire (POPEQ) is an 11-item core measure of psychiatric out-patients experiences of the perceived outcome of the treatment, the quality of interaction with the clinician, and the quality of information provision. The POPEQ was found to have evidence for reliability and validity following the application of classical test theory but has not previously been assessed by Rasch analysis.</p> <p>Methods</p> <p>Two national postal surveys of psychiatric outpatients took place in Norway in 2004 and 2007. The performance of the POPEQ, including item functioning and differential item functioning, was assessed by Rasch analysis. Principal component analysis of item residuals was used to assess the presence of subdimensions.</p> <p>Results</p> <p>6,677 (43.3%) and 11,085 (35.2%) psychiatric out patients responded to the questionnaire in 2004 and 2007, respectively. All items in the scale were retained after the Rasch analysis. The resulting scale had reasonably good fit to the Rasch model. The items performed the same for the two survey years and there was no differential item functioning relating to patient characteristics. Principal component analysis of the residuals confirmed that the measure to a high degree is unidimensional. However, the data also reflects three potential subscales, each relating to one of the three included aspects of health care.</p> <p>Conclusions</p> <p>The POPEQ had excellent psychometric properties and Rasch analysis further supported the construct validity of the scale by also identifying the three subdimensions originally included as components in the instrument development. The 11-item instrument is recommended in future research on psychiatric out-patient experiences. Future development may lead to the construction of more precise measures of the three subdomains that the POPEQ is based on.</p

The Generic Short Patient Experiences Questionnaire (GS-PEQ): identification of core items from a survey in Norway

<p>Abstract</p> <p>Background</p> <p>Questionnaires are commonly used to collect patient, or user, experiences with health care encounters; however, their adaption to specific target groups limits comparison between groups. We present the construction of a generic questionnaire (maximum of ten questions) for user evaluation across a range of health care services.</p> <p>Methods</p> <p>Based on previous testing of six group-specific questionnaires, we first constructed a generic questionnaire with 23 items related to user experiences. All questions included a "not applicable" response option, as well as a follow-up question about the item's importance. Nine user groups from one health trust were surveyed. Seven groups received questionnaires by mail and two by personal distribution. Selection of core questions was based on three criteria: applicability (proportion "not applicable"), importance (mean scores on follow-up questions), and comprehensiveness (content coverage, maximum two items per dimension).</p> <p>Results</p> <p>1324 questionnaires were returned providing subsample sizes ranging from 52 to 323. Ten questions were excluded because the proportion of "not applicable" responses exceeded 20% in at least one user group. The number of remaining items was reduced to ten by applying the two other criteria. The final short questionnaire included items on outcome (2), clinician services (2), user involvement (2), incorrect treatment (1), information (1), organisation (1), and accessibility (1).</p> <p>Conclusion</p> <p>The Generic Short Patient Experiences Questionnaire (GS-PEQ) is a short, generic set of questions on user experiences with specialist health care that covers important topics for a range of groups. It can be used alone or with other instruments in quality assessment or in research. The psychometric properties and the relevance of the GS-PEQ in other health care settings and countries need further evaluation.</p

Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders ("conditions") then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40-50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Evaluation of dendritic cells loaded with apoptotic cancer cells or expressing tumour mRNA as potential cancer vaccines against leukemia

Background Leukemia is a clonal disorder characterized by uncontrolled proliferation of haematopoietic cells, and represents the most common form of cancer in children. Advances in therapy for childhood leukemia have relied increasingly on the use of high-dose chemotherapy often combined with stem-cell transplantation. Despite a high success rate and intensification of therapy, children still suffer from relapse and progressive disease resistant to further therapy. Thus, novel forms of therapy are required. Methods This study focuses on dendritic cell (DC) vaccination of childhood leukemia and evaluates the in vitro efficacy of different strategies for antigen loading of professional antigen-presenting cells. We have compared DCs either loaded with apoptotic leukemia cells or transfected with mRNA from the same leukemia cell line, Jurkat E6, for their capacity to induce specific CD4+ and CD8+ T-cell responses. Monocyte-derived DCs from healthy donors were loaded with tumor antigen, matured and co-cultured with autologous T cells. After one week, T-cell responses against antigen-loaded DCs were measured by enzyme-linked immunosorbent spot (ELISPOT) assay. Results DCs loaded with apoptotic Jurkat E6 cells or transfected with Jurkat E6-cell mRNA were both able to elicit specific T-cell responses in vitro. IFNγ-secreting T cells were observed in both the CD4+ and CD8+ subsets. Conclusion The results indicate that loading of DCs with apoptotic leukemia cells or transfection with tumour mRNA represent promising strategies for development of cancer vaccines for treatment of childhood leukemia

The TCR-Binding Region of the HLA Class I α2 Domain Signals Rapid Fas-Independent Cell Death: A Direct Pathway for T Cell-Mediated Killing of Target Cells?

AbstractTCR binding to an MHC class I/peptide complex is a central event in CTL-mediated elimination of target cells. In this study, we demonstrate that specific activation of the TCR-binding region of the HLA-A2 class I α2 domain induces apoptotic cell death. mAbs to this region rapidly induced apoptosis of HLA-A2-expressing Jurkat E11 cells, as determined by morphologic changes, phosphatidylserine exposure on the cell surface, and propidium iodide uptake. In contrast, apoptosis was not induced following culture with mAbs directed to other regions of the class I molecule. Death signaling by class I molecules is apparently dependent on coreceptor activation, as apoptosis is also signaled by HLA-A2 molecules, where the intracytoplasmic residues were deleted. HLA class I α2-mediated cell death appeared to proceed independent of the Fas pathway. Compared with apoptotic signaling by Fas ligation, HLA class I α2-mediated responses displayed a faster time course and could be observed within 30 min. Furthermore, class I α2-induced cell death did not involve observable DNA fragmentation. The apoptotic response was not affected significantly by peptide inhibitors of IL-1β converting enzyme (ICE)-like proteases and CPP32. Taken together, activation of the TCR-binding domain of the class I α2 helix may result in apoptotic signaling apparently dependent on a novel death pathway. Thus, target HLA class I molecules may directly signal apoptotic cell death following proper ligation by the TCR.</jats:p