Rabl's model of the interphase chromosome arrangement tested in Chinise hamster cells by premature chromosome condensation and laser-UV-microbeam experiments

In 1885 Carl Rabl published his theory on the internal structure of the interphase nucleus. We have tested two predictions of this theory in fibroblasts grown in vitro from a female Chinese hamster, namely (1) the Rabl-orientation of interphase chromosomes and (2) the stability of the chromosome arrangement established in telophase throughout the subsequent interphase. Tests were carried out by premature chromosome condensation (PCC) and laser-UV-microirradiation of the interphase nucleus. Rabl-orientation of chromosomes was observed in G1 PCCs and G2 PCCs. The cell nucleus was microirradiated in G1 at one or two sites and pulse-labelled with 3H-thymidine for 2h. Cells were processed for autoradiography either immediately thereafter or after an additional growth period of 10 to 60h. Autoradiographs show unscheduled DNA synthesis (UDS) in the microirradiated nuclear part(s). The distribution of labelled chromatin was evaluated in autoradiographs from 1035 cells after microirradiation of a single nuclear site and from 253 cells after microirradiation of two sites. After 30 to 60h postincubation the labelled regions still appeared coherent although the average size of the labelled nuclear area fr increased from 14.2% (0h) to 26.5% (60h). The relative distance dr, i.e. the distance between two microirradiated sites divided by the diameter of the whole nucleus, showed a slight decrease with increasing incubation time. Nine metaphase figures were evaluated for UDS-label after microirradiation of the nuclear edge in G1. An average of 4.3 chromosomes per cell were labelled. Several chromosomes showed joint labelling of both distal chromosome arms including the telomeres, while the centromeric region was free from label. This label pattern is interpreted as the result of a V-shaped orientation of these particular chromosomes in the interphase nucleus with their telomeric regions close to each other at the nuclear edge. Our data support the tested predictions of the Rabl-model. Small time-dependent changes of the nuclear space occupied by single chromosomes and of their relative positions in the interphase nucleus seem possible, while the territorial organization of interphase chromosomes and their arrangement in general is maintained during interphase. The present limitations of the methods used for this study are discussed

Outcomes of International Service Learning (ISL): Alumni Perspectives

Service learning is an active method that combines academic knowledge and hands-on experience while serving a community. Service learning is well established within occupational therapy (OT) and allied health education, as many institutions have organized both domestic and international service learning experiences. Literature supports student benefits of participation in international service learning (ISL), but limited literature exists on the long-term impact of participation in ISL throughout allied health education. Many OT students participate in ISL during their education, but there is limited literature on the impact of an ISL experience on participants’ careers in OT. In this qualitative study, an online survey was distributed to past participants of an ISL trip of an OT program in the Midwest. Of the 100 subjects, 30 completed the survey. Researchers used conventional content analysis to extract themes from the data. Two themes were identified: (1) evolving professional self and (2) transformative personal experience. Subthemes of the evolving professional self theme included: (1) desire to work with vulnerable populations, (2) professional soft skill development, and (3) acquisition of knowledge and skills. Results indicate that benefits are maintained after graduation signifying that participation in ISL may have a sustained, lasting influence on OT practitioners. ISL supports the values of OT education by shaping professional identity through active, diverse learning and self-reflection to promote lifelong learning. Results broaden the profession’s understanding of the outcomes of ISL post-graduation and inform ISL best practice standards within OT education

FGF23 in Acute and Chronic Illness

FGF23 is a bone-derived phosphaturic hormone that may become a useful biomarker for the identification of high-risk patients in chronic but also acute disease. It rises early in chronic kidney disease and is strongly and independently associated with excess morbidity and mortality. Emerging data suggest that FGF23 is also elevated in different scenarios of acute illness. In this review, we give an overview on the role of this interesting disease marker and potential and proven interventional strategies and discuss a blueprint for future research

Severe rhabdomyolysis in homozygote carnitine palmitoyltransferase II deficiency

Carnitine palmitoyltransferase II (CPT II) deficiency represents an inherited defect in mitochondrial long-chain fatty acid oxidation. Rhabdomyolysis with necrosis of muscle is caused by the destruction of skeletal muscle and leads to systemic, multiorgan complications due to the release of intracellular muscle components. Severe rhabdomyolysis may be triggered by combination of a genetic predisposition, including CPT II deficiency, with additionally acting causes. Generally, patients with CPT II deficiency are rarely clinical recognized and reported. We describe a patient presenting severe rhabdomyolysis due to urosepsis, who, in genetic testing, demonstrated the homozygous CPT II deficiency (c.338C>T, p.Ser113Leu) mutation. The diagnosis of CPT II deficiency helped this patient to put the symptoms into context, and this reduced myopathy and the risk of recurring rhabdomyolysis. We report on this patient to increase awareness of diagnostic and medical management in CPT II deficiency

Food malabsorption/intolerance complaints triggered by primary epiploic appendagitis

Primary epiploic appendagitis (PEA) is an uncommon and self-limiting cause of acute or subacute abdominal complaints. The diagnosis of PEA, with its characteristic appearance, is made with computed tomography (CT). This report describes a patient seven months after a CT-confirmed diagnosis of PEA. Because of persistent and recurring, functional, non-specific abdominal complaints, food intolerance/malabsorption was investigated. Fructose malabsorption combined with histamine intolerance was found. A registered dietician helped develop an individually-tailored diet to address the problem. Within four days of beginning the fructose-free and histamine-reduced diet, the patient’s complaints resolved. In conclusion, abdominal symptoms caused by fructose malabsorption and histamine intolerance may have been triggered by PAE in this patient

Long time blood-transfusion trend in a European general hospital

Reports about long-time transfusion trends in Austrian hospitals are rare. In our hospital, we implemented an algorithm of preoperative anemia management as part of a patient blood management (PBM) program in October 2011. Anemic individuals with elective surgery underwent an adequate preoperative anemia classification and treatment with erythropoietin and intravenous iron. The aim of this study was to assess red blood cell (RBC), platelet and plasma transfusions before and after implementation of an anemia management program in a general hospital in Austria. This retrospective study evaluated a 12-year trend (2006 – 2017) of RBC, platelet and plasma transfusions in an Austrian general hospital comprising a 6-year period before (2006 – 2011) and a 6-year period after (2012 – 2017) the implementation of an algorithm-guided anemia management. From overall 49,142 transfused RBC units between 2006 - 2017, 22,745 units were transfused in the post-implementation period compared to 26,397 units before PBM initiation (-13.8 %). The plasma unit use decreased also distinctly (787 vs. 1065 units, - 26.1 %) in the period after PBM implementation, whereas a slight decrease of platelet concentration use (807 vs. 843 units, - 4.3 %) was observed, only. This study demonstrates a 12-year pattern of blood use in an Austrian hospital with a distinct decreasing trend of transfused RBC and plasma units during this period. The implementation of PBM activities decreased the need of blood utilization at our institution. Further initiatives are needed to continue this trend in the next years

Assessment of trimethylamine-N-oxide at the blood-cerebrospinal fluid barrier

Recently, the microbiome-derived trimethylamine-N-oxide (TMAO) was shown to be present in human cerebrospinal fluid (CSF). However, data on the potential of TMAO crossing the blood-CSF barrier are still lacking. This retrospective study aimed at investigating possible associations between the CSF/serum albumin (QALB) and TMAO (QTMAO) quotient and evaluating QTMAO values in individuals with and without blood-CSF barrier dysfunction. A total of 290 patients, who underwent diagnostic lumbar puncture with QALB and QTMAO determination, were evaluated. Serum and CSF TMAO measurements were performed on a tandem mass spectrometry SCIEX QTRAP 4500 (Applied Biosystems, Framingham, MA, USA) coupled with an Agilent 1260 Infinity HPLC system (Agilent Technologies Santa Clara, CA, USA). Serum and CSF albumin were measured on the Atellica® NEPH 630 system (Siemens Healthineers, Erlangen, Germany). CSF TMAO levels were positively correlated with serum TMAO levels (ρ = 0.709, p < 0.001). The QALB was significantly associated with the QTMAO (ß-coefficient = 0.312; p < 0.001). A total of 117 patients with blood-CSF barrier dysfunction had significantly higher median (Q1 – Q3) QTMAO values (4.7 (2.8 – 7.5) vs. 3.8 (2.5 – 5.7) x 10-1, p = 0.002) compared to 173 individuals with normal blood-CSF barrier function. CSF and serum TMAO concentrations were significantly associated in 290 CSF/serum pairs from lumbar punctures of clinical routine. QALB showed a relevant influence on QTMAO. Present results indicate that TMAO may cross the blood-CSF barrier

Interleukin-6 is associated with tryptophan metabolism and signs of depression in individuals with carbohydrate malabsorption

The aim of the present study was to investigate possible associations between interleukin-6 (IL-6), interferon-gamma (INF-γ), tumor necrosis factor-alpha (TNF-α), lactoferrin and lipopolysaccharide binding protein (LBP) with TRP metabolism and signs of depression in a large cohort of outpatients referred for carbohydrate malabsorption testing. Serum concentrations of IL-6, INF-γ, TNF-α, lactoferrin, LBP, tryptophan (TRP), kynurenine (KYN) and kynuric acid were determined in 250 adults referred for lactose and fructose malabsorption testing. All participants filled out the Beck Depression Inventory (BDI). Serum IL-6 levels were positively correlated with the BDI score (p = 0.001, ρ = 0.205) and indicators of TRP metabolism (KYN/TRP ratio, KYN) (P-values 13 showed significantly higher IL-6 serum levels (1.7 [1.0 – 2.8] vs. 1.1 [0.8 – 1.7] pg/mL, p < 0.001) compared to 115 individuals with a BDI score ≤ 13. LBP showed a positive correlation with the KYN/TRP ratio (p = 0.005, ρ = 0.177). IL-6 and LBP were associated with indicators of TRP metabolism. IL-6 was found to be linked to signs of depression. Individuals with the presence of depressive symptoms showed higher serum IL-6 levels compared to individuals without depressive symptoms