Myeloma bone disease imaging on a 1st-generation clinical photon-counting detector CT vs. 2nd-generation dual-source dual-energy CT.

OBJECTIVE: Subjective and objective image quality comparison of bone microstructure and disease-related abnormalities in multiple myeloma patients using a 1st-generation dual-source photon-counting detector CT(DS-PCD-CT) and a 2nd-generation dual-source dual-energy (energy-integrating detector) CT (DS-EID-CT). METHODS: Fifty multiple myeloma patients (mean age 67.7 ± 10.9 years,16 females) were prospectively enrolled. Unenhanced whole-body CTs were clinically indicated and performed on DS-EID-CT and DS-PCD-CT (median time difference: 12 months). DS-PCD-CT was performed in Quantumplus UHR mode and DS-EID-CT was performed using dual-energy mode. DS-PCD-CT kernel was set at Br64 with Quantum iterative reconstruction strength Q1; for DS-EID-CT a comparable I70f kernel with SAFIRE iterative reconstruction strength 1 was used. Two independent radiologists assessed image quality subjectively using a 5-point Likert scale considering delineation and sharpness of trabecular bone and lytic bone lesions in the spine and pelvic bones. Additionally, ImageJ was used for quantification of bony septa inside the cancellous bone and through or the edges of osteolysis. RESULTS: Overall quality as well as detectability and sharpness in the delineation of lytic bone lesions were superior for DS-PCD-CT compared with DS-EID-CT (p < 0.0001). The inter-reader agreement for subjective image quality readings showed excellent consistency(α = 94.2-98.8). CTDI and DLP mean values for DS-PCD-CT and DS-EID-CT were 1107.4 ± 247.6 mGy*cm and 8.2 ± 1.8 mGy vs. 1344.3 ± 204.6 mGy*cm and 10.1 ± 1.9 mGy. The quantitative metric for bone microstructure in the femoral head showed significantly better visualization of trabeculae in DS-PCD-CT compared with DS-EID-CT (p < 0.0001). Quantitative analyses of edge sharpness of osteolysis showed significant steeper edges for DS-PCD-CT (p < 0.0001). CONCLUSION: DS-PCD-CT significantly improves spatial resolution of bony microstructure and lytic bone lesions compared to DS-EID-CT. KEY POINTS: • Application of photon-counting detector CT is superior to dual-source dual-energy integrating detector in clinical workup of multiple myeloma patients. • Compared to energy integrating detectors, photon-counting detectors significantly increase the spatial resolution of bone microstructure including disease-related lytic bone lesions in patients with multiple myeloma.

The throwing shoulder in youth elite handball: adaptions of inferior but not anterior capsule thickness differ between the two sexes.

The aim was to investigate side-to-side and sex differences of anterior and inferior capsule thickness (ACT, ICT) between the throwing and non-throwing shoulder (TS, NTS) in youth elite handball players. 125 youth female and male elite handball players (14.1±0.7yo) were assessed for ACT and ICT by ultrasound . ACT measurement was performed from anterior (3 o'clock) in upright position and for ICT from inferior (6 o'clock) in supine position. Measurements of ICT in the TS of all athletes (1.4±0.2 mm) differed significantly but marginally to those in the NTS (1.3±0.2 mm) (p = 0.001). Female (1.2±0.2 mm vs. 1.3±0.2 mm; p = 0.007) but not male youth players (1.4±0.2 mm vs. 1.4±0.2 mm, p = n.s.) demonstrated slight differences in ICT in the TS compared with the NTS. Although significant, the thickness in the TS compared to the NTS was within the measurement accuracy of the ultrasonic assessment. No difference in ACT was observed in the TS (1.4±0.3 mm) compared to the NTS (1.4±0.3 mm) for both sexes (n.s.).In conclusion, the anterior and inferior capsule thickness in youth elite handball athletes is not or only marginally different between throwing and non-throwing shoulders.

Fluid-based augmentation of magnetic resonance visualization of interventional devices.

PURPOSE: To evaluate the transient artifact augmentation of microtubes in magnetic resonance imaging by fluid injection. METHODS: Twenty-one fluorinated ethylene propylene catheters (inner diameter 760 µm) were filled with three different contrast media at various concentrations (Ferucarbotran, Resovist®, Bayer Schering Pharma; Manganese dichloride, MnCl2, Sigma-Aldrich; Gadobutrol, Gadovist®, Bayer Schering Pharma). Artifact appearance was determined in an ex vivo phantom at 1.5 T using three different sequences: T1-weighted three-dimensional volume interpolated breath-hold examination, T2-weighted turbo spin echo, and T1-weighted fast low angle shot. Catheter angulation to the main magnetic field (B0) was varied. Influence of parameters on artifact diameters was assessed with a multiple linear regression similar to an analysis of variance. RESULTS: Artifact diameter was significantly influenced by the contrast agent (p < 0.001), concentration of the contrast agent (p < 0.001), angulation of the phantom to B0 with the largest artifact at 90° (p < 0.001), and encoding direction with a larger diameter in phase encoding direction (PED, p < 0.001). Mean artifact diameters at 90° angulation to B0 in PED were 18.5 ± 5.4 mm in 0.5 mmol/ml Ferucarbotran, 8.7 ± 2.5 mm in 1 mmol/ml Gadobutrol, and 11.6 ± 4.6 mm in 5 mmol/ml MnCl2 . CONCLUSIONS: Fluid-based contrast agents might be applied to interventional devices and thus temporarily augment the artifact ensuring both visibility and safe navigation.

Increased posterior shoulder capsule thickness in youth elite handball players: a sonographic investigation.

PURPOSE: Range of motion adaptations in the shoulders of overhead throwing athletes have been reported, but knowledge about the development of soft-tissue adaptations is limited. The purpose of this study was to investigate differences in posterior shoulder capsule thickness and internal rotation between the throwing and non-throwing shoulder. METHODS: On the basis of the sample size calculation, we assessed 63 youth elite handball players (33 boys and 30 girls, mean age: 13.6 ± 0.9 years) for glenohumeral internal and external rotational range of motion, humeral retrotorsion, and posterior capsule thickness (PCT) with a manual goniometer and a portable ultrasound device and calculated sports-specific differences between the throwing and non-throwing shoulder as well as correlations with PCT. RESULTS: Youth handball players showed side-to-side differences in internal rotation, external rotation, and humeral retrotorsion between the throwing and non-throwing shoulder. Posterior shoulder capsules were 1.21 times thicker (95% confidence interval: 1.1-1.3) in the throwing shoulder than in the non-throwing shoulder (1.3 ± 0.3 mm vs. 1.2 ± 0.2 mm, P < .0001). Loss of internal rotation did not correlate with PCT. CONCLUSIONS: In youth elite handball athletes, posterior shoulder tightness and subsequent sports-specific loss of internal rotation in the throwing shoulder are not related to PCT. Thus, in this age class, other (soft-tissue) factors must be responsible for this condition.

Rubisco and carbon-concentrating mechanism co-evolution across chlorophyte and streptophyte green algae.

Green algae expressing a carbon-concentrating mechanism (CCM) are usually associated with a Rubisco-containing micro-compartment, the pyrenoid. A link between the small subunit (SSU) of Rubisco and pyrenoid formation in Chlamydomonas reinhardtii has previously suggested that specific RbcS residues could explain pyrenoid occurrence in green algae. A phylogeny of RbcS was used to compare the protein sequence and CCM distribution across the green algae and positive selection in RbcS was estimated. For six streptophyte algae, Rubisco catalytic properties, affinity for CO2 uptake (K0.5 ), carbon isotope discrimination (δ13 C) and pyrenoid morphology were compared. The length of the ßA-ßB loop in RbcS provided a phylogenetic marker discriminating chlorophyte from streptophyte green algae. Rubisco kinetic properties in streptophyte algae have responded to the extent of inducible CCM activity, as indicated by changes in inorganic carbon uptake affinity, δ13 C and pyrenoid ultrastructure between high and low CO2 conditions for growth. We conclude that the Rubisco catalytic properties found in streptophyte algae have coevolved and reflect the strength of any CCM or degree of pyrenoid leakiness, and limitations to inorganic carbon in the aquatic habitat, whereas Rubisco in extant land plants reflects more recent selective pressures associated with improved diffusive supply of the terrestrial environment.

MR-guided microwave ablation in hepatic malignancies: clinical experiences from 50 procedures.

Purpose: To investigate technical success, technique efficacy, safety and outcome of MR-guided microwave ablation (MWA) in hepatic malignancies.Material and methods: In this prospective IRB-approved study, patients scheduled for percutaneous treatment of hepatic malignancies underwent MR-guided MWA in a closed-bore 1.5 T MR system. Technical success was assessed on post-procedural MR control imaging. Technique efficacy was evaluated 4 weeks after the procedure on multi-parametric MRI. Assessment of safety followed the Society of Interventional Radiology grading system. Kaplan-Meier survival estimates were calculated to evaluate overall survival (OS), time to local tumor progression (TLTP), and time to non-target progression (TNTP).Results: Between 2015 and 2019, 47 patients (60.5 ± 12.2 years; 39 male) underwent 50 procedures for 58 hepatic tumors (21 hepatocellular carcinomas; 37 metastases). Mean target tumor size was 16 ± 7mm (range: 6-39 mm). Technical success and technique efficacy were 100% and 98%, respectively. Lesions were treated using 2.6 applicator positions (range: 1-6). Mean energy, ablation duration per tumor, and procedure duration were 43.2 ± 23.5 kJ, 26.7 ± 13.1 min and 211.2 ± 68.7 min, respectively. 10 minor (20%) and 3 major (6%) complications were observed. Median post-interventional hospital admission was 1 day (range: 1-19 days). Median OS was 41.6 (IQR: 26.4-) months. Local recurrence occurred after 4 procedures (8%) with TLTP ranging between 3.1 and 41.9 months. Non-target recurrence was observed in 64% of patients after a median TNTP of 13.8 (IQR 2.3-) months.Conclusion: MR-guided MWA allows for safe and successful treatment of hepatic malignancies with a high technique efficacy however with relatively long procedure durations.

Assessment of interpretation of paediatric skeletal radiographs in the emergency room.

AIM: To assess the performance of paediatric skeletal radiography interpretation in the emergency department. MATERIALS AND METHODS: In a large paediatric referral centre, data from trauma patients with initially misdiagnosed skeletal radiography was collected from October 2014 to June 2015. Data analysis focused on demographic data, region of the injury and clinical consequences as well as outcome of treatment. RESULTS: In 125 of 2,316 patients aged from 1-17 years an initial misdiagnosis was documented (5.4%). Misdiagnosis was detected and corrected the next day in a routine review attended by an experienced paediatric radiologist. False-negative interpretation (missed fracture) was found in 62 and false-positive (overdiagnosis) interpretation in 63 patients. The highest error rate was found in elbow radiography (12%) followed by wrist (8%), fingers (4.5%), metacarpus (4.2%), and toes (3.5%). The most frequently missed fracture was supracondylar elbow fracture (n=12). In case of initially missed fractures treatment was adjusted delayed the next day. In none of these patients, were repositioning or open surgical procedures necessary. No misdiagnosis resulted in additional morbidity. CONCLUSION: Misinterpretation of paediatric skeletal radiography by paediatric emergency physicians occurred frequently. The majority of diagnostic errors occurred in a few regions. None of these misdiagnoses negatively affected patients' health. A routine review by an experienced paediatric radiologist is mandatory, but may suffice the next day.

A repeat protein links Rubisco to form the eukaryotic carbon-concentrating organelle.

Biological carbon fixation is a key step in the global carbon cycle that regulates the atmosphere's composition while producing the food we eat and the fuels we burn. Approximately one-third of global carbon fixation occurs in an overlooked algal organelle called the pyrenoid. The pyrenoid contains the CO2-fixing enzyme Rubisco and enhances carbon fixation by supplying Rubisco with a high concentration of CO2 Since the discovery of the pyrenoid more that 130 y ago, the molecular structure and biogenesis of this ecologically fundamental organelle have remained enigmatic. Here we use the model green alga Chlamydomonas reinhardtii to discover that a low-complexity repeat protein, Essential Pyrenoid Component 1 (EPYC1), links Rubisco to form the pyrenoid. We find that EPYC1 is of comparable abundance to Rubisco and colocalizes with Rubisco throughout the pyrenoid. We show that EPYC1 is essential for normal pyrenoid size, number, morphology, Rubisco content, and efficient carbon fixation at low CO2 We explain the central role of EPYC1 in pyrenoid biogenesis by the finding that EPYC1 binds Rubisco to form the pyrenoid matrix. We propose two models in which EPYC1's four repeats could produce the observed lattice arrangement of Rubisco in the Chlamydomonas pyrenoid. Our results suggest a surprisingly simple molecular mechanism for how Rubisco can be packaged to form the pyrenoid matrix, potentially explaining how Rubisco packaging into a pyrenoid could have evolved across a broad range of photosynthetic eukaryotes through convergent evolution. In addition, our findings represent a key step toward engineering a pyrenoid into crops to enhance their carbon fixation efficiency.

Detailed comparison of retroviral vectors and promoter configurations for stable and high transgene expression in human induced pluripotent stem cells.

Correction of patient-specific induced pluripotent stem cells (iPSC) upon gene delivery through retroviral vectors offers new treatment perspectives for monogenetic diseases. Gene-modified iPSC clones can be screened for safe integration sites and differentiated into transplantable cells of interest. However, the current bottleneck is epigenetic vector silencing. In order to identify the most suitable retroviral expression system in iPSC, we systematically compared vectors from different retroviral genera, different promoters and their combination with ubiquitous chromatin opening elements (UCOE), and several envelope pseudotypes. Lentiviral vectors (LV) pseudotyped with vesicular stomatitis virus glycoprotein were superior to gammaretroviral and alpharetroviral vectors and other envelopes tested. The elongation factor 1α short (EFS) promoter mediated the most robust expression, whereas expression levels were lower from the potent but more silencing-prone spleen focus forming virus (SFFV) promoter. Both full-length (A2UCOE) and minimal (CBX3) UCOE juxtaposed to two physiological and one viral promoter reduced transgene silencing with equal efficiency. However, a promoter-specific decline in expression levels was not entirely prevented. Upon differentiation of transgene-positive iPSC into endothelial cells, A2UCOE.EFS and CBX3.EFS vectors maintained highest transgene expression in a larger fraction of cells as compared with all other constructs tested here. The function of UCOE diminished, but did not fully counteract, vector silencing and possibilities for improvements remain. Nevertheless, the CBX3.EFS in a LV background exhibited the most promising promoter and vector configuration for both high titer production and long-term genetic modification of human iPSC and their progeny.

Rubisco small subunits from the unicellular green alga Chlamydomonas complement Rubisco-deficient mutants of Arabidopsis.

Introducing components of algal carbon concentrating mechanisms (CCMs) into higher plant chloroplasts could increase photosynthetic productivity. A key component is the Rubisco-containing pyrenoid that is needed to minimise CO2 retro-diffusion for CCM operating efficiency. Rubisco in Arabidopsis was re-engineered to incorporate sequence elements that are thought to be essential for recruitment of Rubisco to the pyrenoid, namely the algal Rubisco small subunit (SSU, encoded by rbcS) or only the surface-exposed algal SSU α-helices. Leaves of Arabidopsis rbcs mutants expressing 'pyrenoid-competent' chimeric Arabidopsis SSUs containing the SSU α-helices from Chlamydomonas reinhardtii can form hybrid Rubisco complexes with catalytic properties similar to those of native Rubisco, suggesting that the α-helices are catalytically neutral. The growth and photosynthetic performance of complemented Arabidopsis rbcs mutants producing near wild-type levels of the hybrid Rubisco were similar to those of wild-type controls. Arabidopsis rbcs mutants expressing a Chlamydomonas SSU differed from wild-type plants with respect to Rubisco catalysis, photosynthesis and growth. This confirms a role for the SSU in influencing Rubisco catalytic properties.

The algal pyrenoid: key unanswered questions.

The confinement of Rubisco in a chloroplast microcompartment, or pyrenoid, is a distinctive feature of most microalgae, and contributes to perhaps ~30 Pg of carbon fixed each year, yet our understanding of pyrenoid composition, regulation, and function remains fragmentary. Recently, significant progress in understanding the pyrenoid has arisen from studies using mutant lines, mass spectrometric analysis of isolated pyrenoids, and advanced ultrastructural imaging of the microcompartment in the model alga Chlamydomonas. The emergence of molecular details in other lineages provides a comparative framework for this review, and evidence that most pyrenoids function similarly, even in the absence of a common ancestry. The objective of this review is to explore pyrenoid diversity throughout key algal lineages and discuss whether common ultrastructural and cellular features are indicative of common functional processes. By characterizing pyrenoid origins in terms of mechanistic and structural parallels, we hope to provide key unanswered questions which will inform future research directions.

Pyrenoid loss impairs carbon-concentrating mechanism induction and alters primary metabolism in Chlamydomonas reinhardtii.

Carbon-concentrating mechanisms (CCMs) enable efficient photosynthesis and growth in CO2-limiting environments, and in eukaryotic microalgae localisation of Rubisco to a microcompartment called the pyrenoid is key. In the model green alga Chlamydomonas reinhardtii, Rubisco preferentially relocalises to the pyrenoid during CCM induction and pyrenoid-less mutants lack a functioning CCM and grow very poorly at low CO2. The aim of this study was to investigate the CO2 response of pyrenoid-positive (pyr+) and pyrenoid-negative (pyr-) mutant strains to determine the effect of pyrenoid absence on CCM induction and gene expression. Shotgun proteomic analysis of low-CO2-adapted strains showed reduced accumulation of some CCM-related proteins, suggesting that pyr- has limited capacity to respond to low-CO2 conditions. Comparisons between gene transcription and protein expression revealed potential regulatory interactions, since Rubisco protein linker (EPYC1) protein did not accumulate in pyr- despite increased transcription, while elements of the LCIB/LCIC complex were also differentially expressed. Furthermore, pyr- showed altered abundance of a number of proteins involved in primary metabolism, perhaps due to the failure to adapt to low CO2. This work highlights two-way regulation between CCM induction and pyrenoid formation, and provides novel candidates for future studies of pyrenoid assembly and CCM function.

Pyrenoid loss in Chlamydomonas reinhardtii causes limitations in CO2 supply, but not thylakoid operating efficiency.

The pyrenoid of the unicellular green alga Chlamydomonas reinhardtii is a microcompartment situated in the centre of the cup-shaped chloroplast, containing up to 90% of cellular Rubisco. Traversed by a network of dense, knotted thylakoid tubules, the pyrenoid has been proposed to influence thylakoid biogenesis and ultrastructure. Mutants that are unable to assemble a pyrenoid matrix, due to expressing a vascular plant version of the Rubisco small subunit, exhibit severe growth and photosynthetic defects and have an ineffective carbon-concentrating mechanism (CCM). The present study set out to determine the cause of photosynthetic limitation in these pyrenoid-less lines. We tested whether electron transport and light use were compromised as a direct structural consequence of pyrenoid loss or as a metabolic effect downstream of lower CCM activity and resulting CO2 limitation. Thylakoid organization was unchanged in the mutants, including the retention of intrapyrenoid-type thylakoid tubules, and photosynthetic limitations associated with the absence of the pyrenoid were rescued by exposing cells to elevated CO2 levels. These results demonstrate that Rubisco aggregation in the pyrenoid functions as an essential element for CO2 delivery as part of the CCM, and does not play other roles in maintenance of photosynthetic membrane energetics.

Introducing an algal carbon-concentrating mechanism into higher plants: location and incorporation of key components.

Many eukaryotic green algae possess biophysical carbon-concentrating mechanisms (CCMs) that enhance photosynthetic efficiency and thus permit high growth rates at low CO2 concentrations. They are thus an attractive option for improving productivity in higher plants. In this study, the intracellular locations of ten CCM components in the unicellular green alga Chlamydomonas reinhardtii were confirmed. When expressed in tobacco, all of these components except chloroplastic carbonic anhydrases CAH3 and CAH6 had the same intracellular locations as in Chlamydomonas. CAH6 could be directed to the chloroplast by fusion to an Arabidopsis chloroplast transit peptide. Similarly, the putative inorganic carbon (Ci) transporter LCI1 was directed to the chloroplast from its native location on the plasma membrane. CCP1 and CCP2 proteins, putative Ci transporters previously reported to be in the chloroplast envelope, localized to mitochondria in both Chlamydomonas and tobacco, suggesting that the algal CCM model requires expansion to include a role for mitochondria. For the Ci transporters LCIA and HLA3, membrane location and Ci transport capacity were confirmed by heterologous expression and H(14) CO3 (-) uptake assays in Xenopus oocytes. Both were expressed in Arabidopsis resulting in growth comparable with that of wild-type plants. We conclude that CCM components from Chlamydomonas can be expressed both transiently (in tobacco) and stably (in Arabidopsis) and retargeted to appropriate locations in higher plant cells. As expression of individual Ci transporters did not enhance Arabidopsis growth, stacking of further CCM components will probably be required to achieve a significant increase in photosynthetic efficiency in this species.

Scale morphometry allows discrimination of European sardine Sardina pilchardus and round sardinella Sardinella aurita and among their local populations.

Landmark-based geometric morphometric analysis revealed differences in scale shape between European sardine Sardina pilchardus and round sardinella Sardinella aurita as well as among the local populations of each species. Fish scale measurements from four different areas in the central and eastern Mediterranean Sea showed that the mean scale shape of the two species using landmark data could be differentiated with high certainty. Populations of S. aurita from the central and eastern Mediterranean Sea could be separated reliably (P < 0·001) with an average discrimination rate of 91%, whereas the average discrimination of the S. pilchardus populations was lower (80%), albeit still high.

Tightly regulated 'all-in-one' lentiviral vectors for protection of human hematopoietic cells from anticancer chemotherapy.

Successful application of gene therapy strategies may require stringently regulated transgene expression. Along this line, we describe a doxycycline (Dox)-inducible 'all-in-one' lentiviral vector design using the pTET-T11 (TII) minimal-promoter and a reverse transactivator protein (rtTA2S-M2) driven by the phosphoglycerate kinase promoter allowing for tight regulation of transgene expression (Lv.TII vectors). Vector design was evaluated in human hematopoietic cells in the context of cytidine deaminase (hCDD)-based myeloprotective gene therapy. Upon Dox administration, a rapid (16-24 h) and dose-dependent (>0.04 µg ml(-1) Dox) onset of transgene expression was detected in Lv.TII.CDD gene-modified K562 cells as well as in primary human CD34(+) hematopoietic cells. Importantly, in both cell models low background transgene expression was observed in the absence of Dox. Functionality of Dox-inducible hCDD expression was demonstrated by >10-fold increase in cytosine arabinoside (1-ß-d-arabinofuranosylcytosine, Ara-C) resistance of Lv.TII.CDD-transduced K562 cells. In addition, Lv.TII.CDD-transduced CD34(+)-derived myeloid cells were protected from up to 300 nm Ara-C (control affected from 50 nm onwards). These data clearly demonstrate the suitability of our self-inactivating lentiviral vector to induce robust, tightly regulated transgene expression in human hematopoietic cells with minimal background activity and highlight the potential of our construct in myeloprotective gene therapy strategies.

Dynamics of carbon-concentrating mechanism induction and protein relocalization during the dark-to-light transition in synchronized Chlamydomonas reinhardtii.

In the model green alga Chlamydomonas reinhardtii, a carbon-concentrating mechanism (CCM) is induced under low CO2 in the light and comprises active inorganic carbon transport components, carbonic anhydrases, and aggregation of Rubisco in the chloroplast pyrenoid. Previous studies have focused predominantly on asynchronous cultures of cells grown under low versus high CO2. Here, we have investigated the dynamics of CCM activation in synchronized cells grown in dark/light cycles compared with induction under low CO2. The specific focus was to undertake detailed time course experiments comparing physiology and gene expression during the dark-to-light transition. First, the CCM could be fully induced 1 h before dawn, as measured by the photosynthetic affinity for inorganic carbon. This occurred in advance of maximum gene transcription and protein accumulation and contrasted with the coordinated induction observed under low CO2. Between 2 and 1 h before dawn, the proportion of Rubisco and the thylakoid lumen carbonic anhydrase in the pyrenoid rose substantially, coincident with increased CCM activity. Thus, other mechanisms are likely to activate the CCM before dawn, independent of gene transcription of known CCM components. Furthermore, this study highlights the value of using synchronized cells during the dark-to-light transition as an alternative means of investigating CCM induction.

Rosiglitazone treatment and cardiovascular disease in the Veterans Affairs Diabetes Trial.

AIMS: To evaluate the relationship between patterns of rosiglitazone use and cardiovascular (CV) outcomes in the Veterans Affairs Diabetes Trial (VADT). METHODS: Time-dependent survival analyses, case-control and 1 : 1 propensity matching approaches were used to examine the relationship between patterns of rosiglitazone use and CV outcomes in the VADT, a randomized controlled study that assessed the effect of intensive glycaemic control on CV outcomes in 1791 patients with type 2 diabetes (T2D) whose mean age was 60.4 ± 9 years. Participants were recruited between 1 December 2000 and 31 May 2003, and were followed for 5-7.5 years (median 5.6) with a final visit by 31 May 2008. Rosiglitazone (4 mg and 8 mg daily) was initiated per protocol in both the intensive-therapy and standard-therapy groups. Main outcomes included a composite CV outcome, CV death and myocardial infarction (MI). RESULTS: Both daily doses of rosiglitazone were associated with lower risk for the primary composite CV outcome [4 mg: hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.49-0.81 and 8 mg: HR 0.60, 95% CI 0.49-0.75] after adjusting for demographic and clinical covariates. A reduction in CV death was also observed (HR 0.25, p < 0.001, for both 4 and 8 mg/day rosiglitazone); however, the effect on MI was less evident for 8 mg/day and not significant for 4 mg/day. CONCLUSIONS: In older patients with T2D the use of rosiglitazone was associated with decreased risk of the primary CV composite outcome and CV death. Rosiglitazone use did not lead to a higher risk of MI.

Rubisco small-subunit α-helices control pyrenoid formation in Chlamydomonas.

The pyrenoid is a subcellular microcompartment in which algae sequester the primary carboxylase, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). The pyrenoid is associated with a CO(2)-concentrating mechanism (CCM), which improves the operating efficiency of carbon assimilation and overcomes diffusive limitations in aquatic photosynthesis. Using the model alga Chlamydomonas reinhardtii, we show that pyrenoid formation, Rubisco aggregation, and CCM activity relate to discrete regions of the Rubisco small subunit (SSU). Specifically, pyrenoid occurrence was shown to be conditioned by the amino acid composition of two surface-exposed α-helices of the SSU: higher plant-like helices knock out the pyrenoid, whereas native algal helices establish a pyrenoid. We have also established that pyrenoid integrity was essential for the operation of an active CCM. With the algal CCM being functionally analogous to the terrestrial C(4) pathway in higher plants, such insights may offer a route toward transforming algal and higher plant productivity for the future.

Visualization of the Long Thoracic Nerve using High-Resolution Sonography.

PURPOSE: The long thoracic nerve (LTN) innervates the serratus anterior muscle (SA) which plays an important role in shoulder function. Evaluation of the LTN has so far been restricted to clinical assessment and partly electromyography and neurography. Progress of high-resolution ultrasound (HRUS) increasingly enables visualization of small peripheral nerves and their pathologies. We therefore aimed at (a) clarifying the possibility of visualization of the LTN from its origin to the most distal point in the supraclavicular region visible and (b) developing an ultrasound protocol for routine use. We further present two cases of patients with LTN pathology. METHODS: The study consisted of two parts: Part 1 included 4 non-enbalmed human bodies in whom the LTN (n = 8) was located and then marked by ink injection. Correct identification was confirmed by anatomical dissection. Part 2 included 20 healthy volunteers whose LTN (n = 40) was assessed independently by two radiologists. Identification of the LTN was defined as consensus in recorded images. RESULTS: LTN was clearly visible in all anatomical specimens and volunteers using HRUS and could be followed until the second slip of the serratus anterior muscle from the supraclavicular region. In anatomical specimens, dissection confirmed HRUS findings. For all volunteers, consensus was obtained. The mean nerve diameter was 1.6 mm ±â€Š0.3 (range 1.1 - 2.1 mm) after the formation of the main trunk. DISCUSSION: We hereby confirm a reliable possibility of visualization of the LTN in anatomical specimens as well as in volunteers. We encourage HRUS of the LTN to be part of the diagnostic work-up in patients presenting with scapular winging, shoulder weakness or pain of unknown origin.