Rapid detection by hydrops panel of Noonan syndrome with PTPN11 mutation (p.Thr73Ile) and persistent thrombocytopenia

Background: Nonimmune hydrops fetalis (NIHF) is still a challenging diagnosis. The differential diagnosis is extensive and the success of identifying a cause depends on the thoroughness of efforts to establish a diagnosis. For the early diagnosis of NIHF, a virtual gene panel diagnostic tool was developed. The female premature baby in question was delivered via emergency cesarean at 30 1 weeks of gestational age (GA) due to rapidly developing NIHF to a healthy mother. The family history was noncontributory. Methods DNA of the family was extracted and sequenced by the virtual hydrops panel with whole-exome sequencing. Results: The hydrops panel revealed Noonan syndrome (NS) with a germline mutation in PTPN11 c.218C>T (p.Thr73Ile). Conclusion: The diagnosis of our patient was rapidly confirmed by the hydrops panel. The variant of c.218C>T (p.Thr73Ile) has not yet been described in literature relating to NIHF. Only a few case reports of this variant are known. This particular mutation is associated with Noonan syndrome, congenital heart defect and persistent thrombocytopenia. Few reveal juvenile myelomonocytic leukemia

Bovine tuberculosis and brucellosis in cattle and African buffalo in the Limpopo National Park, Mozambique

Bovine tuberculosis (BTB) and brucellosis are prevalent in buffaloes of the Kruger National Park (KNP, South Africa). Both diseases were considered to have no or a very low prevalence in wildlife and livestock in and around the Limpopo National Park (LNP, Mozambique). The same applies for tuberculosis in Gonarezhou National Park (GNP, Zimbabwe), but just recently, BTB was detected in buffaloes in the GNP and fears arose that the disease might also spread to the LNP as a result of the partial removal of the fences between the three parks to form the Great Limpopo Transfrontier Park. To assess the status of both diseases in and around LNP, 62 buffaloes were tested for bovine tuberculosis (BTB) and bovine brucellosis. The percentage of positive BTB reactors in buffalo was 8.06% using BovidTB Stat-Pak and 0% with BOVIGAM IFN-c test and IDEXX ELISA. The brucellosis seroprevalence in buffalo was found to be 17.72% and 27.42% using Rose Bengal Test (RBT) and ELISA, respectively. In addition, 2445 cattle in and around the LNP were examined for BTB using the single intradermal cervical comparative tuberculin test (SICCT), and an apparent prevalence of 0.98% was found with no significant difference inside (0.5%) and outside (1.3%) the park. This is the first published report on the presence of positive reactors to BTB and bovine brucellosis in buffalo and cattle in and outside the LNP. Monitoring the wildlife–livestock–human interface of zoonotic high-impact diseases such as BTB and brucellosis is of outmost importance for the successful implementation and management of any transfrontier park that aims to improve the livelihoods of the local communities.German Research Foundation (DFG).http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1865-16822016-12-31hb2016Veterinary Tropical Disease

Identifizierung und Molekularbiologische Charakterisierung nukleärer Zufalls-Knockout-Mutanten mit defekter LHCII state transition in Chlamydomonas reinhardtii

Schönfeld C. Identifizierung und Molekularbiologische Charakterisierung nukleärer Zufalls-Knockout-Mutanten mit defekter LHCII state transition in Chlamydomonas reinhardtii. Bielefeld; 2003

A clinical radiological score for femoral head grafts - Establishment of the Tabea FK score to ensure the quality of human femoral head grafts

Einleitung: Die Transplantation humaner Femurköpfe (FK) ist ein etabliertes Verfahren in der knöchernen Defektrekonstruktion bei orthopädischen und unfallchirurgischen Eingriffen, wobei eine standardisierte morphologische Qualitätsbewertung des Femurkopfgewebes bisher kaum erfolgt. Material und Methoden: Bei 105 Patienten wurde der jeweilige FK im Rahmen einer Hüft-TEP standardisiert entnommen. Anhand klinischer und radiologischer Kriterien (Vorhandensein von Zysten, Nekrosen, Verkalkungen, Deformitäten und Osteoporose) wurde der FK mittels des Tabea-FK-Scores in drei Kategorien (beste/mittlere/schlechte Qualität) eingeteilt. Hiernach erfolgte eine zweite, makroskopische Einteilung der Qualität des in drei Schichten aufgesägten FK. Dieser „Makro-Score“ diente als Goldstandard. Ergänzend wurden eine periphere quantitative Computertomographie (pQCT) sowie histologische Untersuchungen durchgeführt. Die Übereinstimmung des Tabea-FK-Scores sowie der Ergebnisse der ergänzenden Untersuchungen mit dem Makro-Score wurde mittels Sensitivitäten und Spezifitäten beurteilt. Ergebnisse: Bei 91/105 Patienten (Alter: 68,4 ± 9,9 Jahre, n = 60 Frauen, n = 31 Männer) wurden die explantierten FK in die Studie eingeschlossen. Die Übereinstimmung zwischen dem primären Tabea-FK-Score und dem Makro-Score in Bezug auf die Unterscheidung mittlere/beste sowie schlechte/mittlere Qualität ist als gut einzustufen (Sensitivität 77 % sowie 81 % und Spezifität 76 % sowie 84 %). Die Übereinstimmung des histologischen Befundes mit dem Makro-Score war insgesamt etwas schlechter und wies in Bezug auf die Unterscheidung mittlere/beste sowie schlechte/mittlere Qualität eine Sensitivität von 85 % sowie 54 % und eine Spezifität von 66 % sowie 97 % auf. Der pQCT-Score wies lediglich bei der Unterscheidung mittlere/beste Qualität eine zufriedenstellende Sensitivität (82 %) auf, während diese bei der Unterscheidung schlechte/mittlere Qualität sowie schlechte/mittlere + beste Qualität <10 % betrug. Diskussion: Die gute Übereinstimmung zwischen primärem Tabea-FK-Score und makroskopischer Zweitbewertung unterstreicht die Fähigkeiten langjährig operativ tätiger Orthopäden, die Qualität der Knochenspongiosa bereits anhand des Röntgenbildes und des intraoperativen Befundes korrekt einzustufen. Insofern kann die Einführung des Tabea-FK-Scores in die Routineabläufe von Knochenbanken als Qualitätssicherungsmaßnahme empfohlen werden.Introduction: Transplantation of cancellous tissue from human femoral heads (FK) is an established method in the reconstruction of bony defects in orthopedic and trauma surgery. Standardized rating systems with respect to the morphological quality of this tissue are not available. Materials and methods: In 91/105 patients who had been a regular, clinically-indicated surgery (arthroplasty of the hip joint) the respective femoral head (FK) was taken under standardized conditions. Using a checklist defined clinical and radiological criteria of FK are judged in terms of their quality (cysts, necrosis, calcification, deformities, osteoporosis) and divided by the Tabea FK score into three classes (best/middle/poor quality). This was followed by a blinded repeated scoring, now as macroscopic assessment of three sawed layers from the same femoral head. The femoral heads are examined by peripheral quantitative computed tomography (pQCT) and a standardized histological examination of the bony tissue. We evaluated the accordance of the Tabea FK score with complementary assessments by calculation of sensitivity and specificity. Results: Femoral heads from 91/105 patients (ages: 68.4 ± 9.9 , n = 60 women, n = 31 men) were explanted and included in the study. The correlation between the primary radiologic clinical score (Tabea FK score) and the macroscopic second review of the sawn FK with respect to middle/best and poor/middle quality was classified as good (sensitivity 77% and 81%, respectively; specificity 76% and 84%, respectively). The correlation of histology and macroscopic second review was worse and in relation to discrimination of middle/best and poor/middle quality had a sensitivity of 85% and 54%, respectively, and a specificity of 66% and 97%, respectively. The pQCT showed a sensitivity of 82% only in discrimination of middle/best, while sensitivity in discrimination of poor/middle and poor/middle + best, respectively, was <10%. Discussion: The corresponding correlation between the primary and the second clinical score was evaluated as good. This emphasizes the long-standing skills of operationally active orthopedic surgeons to classify the quality of cancellous bone correctly already on the basis of X‑ray images and intraoperative findings. In this respect, the introduction of the Tabea FK score as a quality assurance tool in the routines of bone banks can be recommended

Metabolic Plasticity of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is one of the most common and life-threatening leukemias. A highly diverse and flexible metabolism contributes to the aggressiveness of the disease that is still difficult to treat. By using different sources of nutrients for energy and biomass supply, AML cells gain metabolic plasticity and rapidly outcompete normal hematopoietic cells. This review aims to decipher the diverse metabolic strategies and the underlying oncogenic and environmental changes that sustain continuous growth, mediate redox homeostasis and induce drug resistance in AML. We revisit Warburg’s hypothesis and illustrate the role of glucose as a provider of cellular building blocks rather than as a supplier of the tricarboxylic acid (TCA) cycle for energy production. We discuss how the diversity of fuels for the TCA cycle, including glutamine and fatty acids, contributes to the metabolic plasticity of the disease and highlight the roles of amino acids and lipids in AML metabolism. Furthermore, we point out the potential of the different metabolic effectors to be used as novel therapeutic targets

PREVALENCE AND CORRELATES OF COST-RELATED MEDICATION NONADHERENCE TO IMMUNOSUPPRESSIVE DRUGS AFTER HEART TRANSPANTATION – THE INTERNATIONAL MULTICENTER CROSSSECTIONAL BRIGHT STUDY REFERENCE

BACKGROUND: Cost-related medication nonadherence (CRMNA) refers to not taking medications as prescribed because of difficulties paying for them. OBJECTIVES: The aims of this study were (1) to assess the prevalence of CRMNA to immunosuppressants in heart transplant recipients internationally and (2) to determine multilevel correlates (patient, center, and healthcare system levels) of CRMNA. METHODS: Using data from the cross-sectional international BRIGHT study, applying multistaged sampling, CRMNA was assessed via 3 self-report items in 1365 patients from 36 heart transplant centers in 11 countries. Cost-related medication nonadherence was defined as any positive answer on any of the 3 items. Healthcare system-level (ie, insurance coverage, out-of-pocket expenditures) and patient-level (ie, intention, perceived financial burden, cost as a barrier, a health belief regarding medication benefits, cost-related self-efficacy, and demographic factors) CRMNA correlates were assessed. Correlates were examined using mixed logistic regression analysis. RESULTS: Across all study countries, CRMNA had an average prevalence of 2.6% (range, 0% [Switzerland/Brazil] to 9.8% [Australia]) and was positively related to being single (odds ratio, 2.29; 95% confidence interval, 1.17-4.47), perceived financial burden (odds ratio, 2.15; 95% confidence interval, 1.55-2.99), and cost as a barrier (odds ratio, 2.60; 95% confidence interval, 1.66-4.07). Four protective factors were identified: white ethnicity (odds ratio, 0.37; 95% confidence interval, 0.19-0.74), intention to adhere (odds ratio, 0.44; 95% confidence interval, 0.31-0.63), self-efficacy (odds ratio, 0.54; 95% confidence interval, 0.43-0.67), and belief about medication benefit (odds ratio, 0.70; 95% confidence interval, 0.57-0.87). Regarding variability, 81.3% was explained at the patient level; 13.8%, at the center level; and 4.8%, at the country level. CONCLUSION: In heart transplant recipients, the CRMNA prevalence varies across countries but is lower than in other chronically ill populations. Identified patient-level correlates are novel (ie, intention to adhere, cost-related barriers, and cost-related self-efficacy) and indicate patient-perceived medication cost burden.status: accepte

Heart transplant centers with multidisciplinary team show a higher level of chronic illness management - Findings from the International BRIGHT Study.

The objectives of this study were to: (1) explore the proportion of HTx centers that have a multidisciplinary team and (2) assess the relationship between multidisciplinarity and the level of chronic illness management (CIM). The International Society for Heart and Lung Transplantation (ISHLT) recommends a multidisciplinary approach in heart transplant (HTx) follow-up care but little is known regarding the proportion of HTx centers that meet this recommendation and the impact on patient care. HTx centers with a multidisciplinary team may offer higher levels of CIM, a care model that has the potential to improve outcomes after HTx. We conducted a secondary analysis of the BRIGHT study, a cross-sectional study in 11 countries. Multidisciplinarity in the 36 HTx centers was assessed through HTx director reports and was defined as having a team that was composed of physician(s), nurse(s), and another healthcare professional (either a social worker, psychiatrist, psychologist, pharmacist, dietician, physical therapist, or occupational therapist). CIM was assessed with the Patient Assessment of Chronic Illness Care (PACIC). Multiple linear regression assessed the relationship between multidisciplinarity and the level of CIM. Twenty-nine (80.6%) of the HTx centers had a multidisciplinary team. Furthermore, multidisciplinarity was significantly associated with higher levels of CIM (β = 5.2, P = 0.042). Majority of the HTx centers follows the ISHLT recommendation for a multidisciplinary approach. Multidisciplinarity was associated with CIM and point toward a structural factor that needs to be in place for moving toward CIM

Heart transplant centers with multidisciplinary team show a higher level of chronic illness management - Findings from the International BRIGHT Study.

OBJECTIVES: The objectives of this study were to: (1) explore the proportion of HTx centers that have a multidisciplinary team and (2) assess the relationship between multidisciplinarity and the level of chronic illness management (CIM). BACKGROUND: The International Society for Heart and Lung Transplantation (ISHLT) recommends a multidisciplinary approach in heart transplant (HTx) follow-up care but little is known regarding the proportion of HTx centers that meet this recommendation and the impact on patient care. HTx centers with a multidisciplinary team may offer higher levels of CIM, a care model that has the potential to improve outcomes after HTx. METHODS: We conducted a secondary analysis of the BRIGHT study, a cross-sectional study in 11 countries. Multidisciplinarity in the 36 HTx centers was assessed through HTx director reports and was defined as having a team that was composed of physician(s), nurse(s), and another healthcare professional (either a social worker, psychiatrist, psychologist, pharmacist, dietician, physical therapist, or occupational therapist). CIM was assessed with the Patient Assessment of Chronic Illness Care (PACIC). Multiple linear regression assessed the relationship between multidisciplinarity and the level of CIM. RESULTS: Twenty-nine (80.6%) of the HTx centers had a multidisciplinary team. Furthermore, multidisciplinarity was significantly associated with higher levels of CIM (β = 5.2, P = 0.042). CONCLUSION: Majority of the HTx centers follows the ISHLT recommendation for a multidisciplinary approach. Multidisciplinarity was associated with CIM and point toward a structural factor that needs to be in place for moving toward CIM