[Outpatient and "Admission-Substituting" Interventions in Vascular Surgery - What is Feasible and Where are the Limits? Previous and New Legal Requirements and their Implementation in Practice]. / Ambulante und stationsersetzende Eingriffe in der Gefäßchirurgie ­ was ist machbar und wo liegen die Grenzen? Bisherige und neue gesetzliche Vorgaben sowie deren Umsetzung in der Praxis.

INTRODUCTION: In vascular surgery too, more services and procedures will have to be shifted from the previous inpatient to the outpatient sector in the future. Therefore, the previous and new legal requirements as well as their implementation in vascular surgery will be explained and evaluated. MATERIAL AND METHODS: Professional policy analysis from a perspective of medical vascular surgery. RESULTS: The AOP catalog from 01.01.2023 was extended by 208 additional OPS codes. The inpatient performance of services which, according to the AOP contract, must be regularly performed on an outpatient basis, are now to be justified on the basis of context factors.A special sector-equivalent remuneration, which is independent of whether the remunerated service is performed on an outpatient or inpatient basis, is a prerequisite for a cost-covering expansion of outpatient operations and inpatient-replacing services. The rehabilitation of primary varicosis under outpatient conditions is undoubtedly the standard. The majority of AV shunt installations are performed as inpatient procedures. No new OPS codes were added to the 2023 AOP catalog for varicose vein, shunt and endovascular surgery. DISCUSSION: The shift of inpatient services to the outpatient sector can be a feasible path, based on the experience of other European countries. However, the structures, economic conditions and incentives should first be created to successfully promote transfer to outpatients. Integrated care offers the possibility for the health insurance funds to conclude contracts with the service providers named in § 140a of the Social Code, paragraph 3, for special care. The use of telemedicine in the sense of tele-premedication or tele-monitoring can be a way to expand outpatient surgery, especially in rural regions. In order to enable therapy concepts from one expert in vascular medicine, the outpatient service billing of interventional procedures must also be demanded by vascular surgeons and specialists. CONCLUSION: The potential to transform inpatient services into the outpatient setting of service provision is realisable in vascular surgery in the core areas of varicose vein surgery, shunt surgery and peripheral interventional procedures under specific conditions.

[Vascular surgery care in rural areas-Adaptation to demographic and epidemiological requirements]. / Gefäßchirurgische Versorgung im ländlichen Raum ­ Anpassung an die demografischen und epidemiologischen Erfordernisse.

Introduction: The demographic development in Germany, especially in Saxony-Anhalt (SA), also poses challenges for vascular surgery, as the incidence of vascular diseases has increased following demographic change. For example, the prevalence of peripheral arterial occlusive disease (PAOD) in industrialised countries is estimated at around 10-20% in people over 60 years of age; thus, the number of people affected will also increase here with demographic change. Especially in rural areas, it seems to be more difficult for patients to reach appropriate specialist treatment. Material and methods: A compact narrative brief review, based on selective references from the current medical-scientific literature and our own experiences from daily practice in setting up a vascular surgery department in a rural area. Results: In 2020, the population in the rural district of Jerichower Land (SA) was approximately 89,403 (male: 44,489; female: 44,914). The age distribution in the age groups relevant for PAOD is as follows: 65-74 years-total, 12.38%; 75 years and older-total, 13.85%; average age, 48.36 years (population density, 56.4/km2). According to the SA Association of Statutory Health Insurance Physicians, there were 605 patients for every doctor in Burg (SA) in 2019.There was a total of 5087 people in need of long-term care in the district in 2019. With such a low population density, low doctor density, high mean age, high proportion of people over 75 years of age and a high number of people in need of care, limited mobility and accessibility to vascular surgery care are to be expected, which was also reflected in the high number of PAOD of stage IV (FONTAINE) in the initial patient clientele.Every establishment of a vascular surgery department is associated with a considerable financial and material investment, which the provider of the facility must be prepared to make.In addition to the material investment, the availability of appropriately qualified staff to implement and maintain continuity of care must also be seriously considered. Conclusion: The high proportion of residents at risk of and suffering from PAOD in a rural area with low population and doctor density allows investment in the establishment of a new vascular surgery department to ensure local care in this patient group with limited mobility and self-help, thus, ultimately from an appropriate health policy perspective but also from the perspective of a relevant revenue outlook.

Role of S100A8/A9 in Platelet-Neutrophil Complex Formation during Acute Inflammation.

Acute respiratory distress syndrome (ARDS) due to pulmonary infections is associated with high morbidity and mortality. Upon inflammation, the alarmin S100A8/A9 is released and stimulates neutrophil recruitment mainly via binding to Toll-like receptor 4 (TLR4). TLR4 is also expressed on platelets, which modulate the immune response through direct interaction with leukocytes. In a murine model of Klebsiella pneumoniae-induced pulmonary inflammation, global S100A9 deficiency resulted in diminished neutrophil recruitment into the lung alveoli and neutrophil accumulation in the intravascular space, indicating an impaired neutrophil migration. A lack of TLR4 on platelets resulted in reduced neutrophil counts in the whole lung, emphasising the impact of TLR4-mediated platelet activity on neutrophil behaviour. Flow cytometry-based analysis indicated elevated numbers of platelet-neutrophil complexes in the blood of S100A9-/- mice. Intravital microscopy of the murine cremaster muscle confirmed these findings and further indicated a significant increase in neutrophil-platelet complex formation in S100A9-/- mice, which was reversed by administration of the S100A8/A9 tetramer. An in vitro bilayer assay simulated the murine alveolar capillary barrier during inflammation and validated significant differences in transmigration behaviour between wild-type and S100A9-/- neutrophils. This study demonstrates the role of S100A8/A9 during platelet-neutrophil interactions and neutrophil recruitment during pulmonary inflammation.

Nanoscale segregation of channel and barrier claudins enables paracellular ion flux.

The paracellular passage of ions and small molecules across epithelia is controlled by tight junctions, complex meshworks of claudin polymers that form tight seals between neighboring cells. How the nanoscale architecture of tight junction meshworks enables paracellular passage of specific ions or small molecules without compromising barrier function is unknown. Here we combine super-resolution stimulated emission depletion microscopy in live and fixed cells and tissues, multivariate classification of super-resolution images and fluorescence resonance energy transfer to reveal the nanoscale organization of tight junctions formed by mammalian claudins. We show that only a subset of claudins can assemble into characteristic homotypic meshworks, whereas tight junctions formed by multiple claudins display nanoscale organization principles of intermixing, integration, induction, segregation, and exclusion of strand assemblies. Interestingly, channel-forming claudins are spatially segregated from barrier-forming claudins via determinants mainly encoded in their extracellular domains also known to harbor mutations leading to human diseases. Electrophysiological analysis of claudins in epithelial cells suggests that nanoscale segregation of distinct channel-forming claudins enables barrier function combined with specific paracellular ion flux across tight junctions.

Remote ischemic preconditioning causes transient cell cycle arrest and renal protection by a NF-κB-dependent Sema5B pathway.

Acute kidney injury increases morbidity and mortality, and previous studies have shown that remote ischemic preconditioning (RIPC) reduces the risk of acute kidney injury after cardiac surgery. RIPC increases urinary high mobility group box protein-1 (HMGB1) levels in patients, and this correlates with kidney protection. Here, we show that RIPC reduces renal ischemia-reperfusion injury and improves kidney function in mice. Mechanistically, RIPC increases HMGB1 levels in the plasma and urine, and HMGB1 binds to TLR4 on renal tubular epithelial cells, inducing transcriptomic modulation of renal tubular epithelial cells and providing renal protection, whereas TLR4 activation on nonrenal cells was shown to contribute to renal injury. This protection is mediated by activation of induction of AMPKα and NF-κB; this induction contributes to the upregulation of Sema5b, which triggers a transient, protective G1 cell cycle arrest. In cardiac surgery patients at high risk for postoperative acute kidney injury, increased HMGB1 and Sema5b levels after RIPC were associated with renal protection after surgery. The results may help to develop future clinical treatment options for acute kidney injury.

Proton-gated anion transport governs macropinosome shrinkage.

Intracellular organelles change their size during trafficking and maturation. This requires the transport of ions and water across their membranes. Macropinocytosis, a ubiquitous form of endocytosis of particular importance for immune and cancer cells, generates large vacuoles that can be followed optically. Shrinkage of macrophage macropinosomes depends on TPC-mediated Na+ efflux and Cl- exit through unknown channels. Relieving osmotic pressure facilitates vesicle budding, positioning osmotic shrinkage upstream of vesicular sorting and trafficking. Here we identify the missing macrophage Cl- channel as the proton-activated Cl- channel ASOR/TMEM206. ASOR activation requires Na+-mediated depolarization and luminal acidification by redundant transporters including H+-ATPases and CLC 2Cl-/H+ exchangers. As corroborated by mathematical modelling, feedback loops requiring the steep voltage and pH dependencies of ASOR and CLCs render vacuole resolution resilient towards transporter copy numbers. TMEM206 disruption increased albumin-dependent survival of cancer cells. Our work suggests a function for the voltage and pH dependence of ASOR and CLCs, provides a comprehensive model for ion-transport-dependent vacuole maturation and reveals biological roles of ASOR.

Loss of a pyridoxal-phosphate phosphatase rescues Arabidopsis lacking an endoplasmic reticulum ATP carrier.

The endoplasmic reticulum (ER)-located ATP/ADP-antiporter (ER-ANT1) occurs specifically in vascular plants. Structurally different transporters mediate energy provision to the ER, but the cellular function of ER-ANT1 is still unknown. Arabidopsis (Arabidopsis thaliana) mutants lacking ER-ANT1 (er-ant1 plants) exhibit a photorespiratory phenotype accompanied by high glycine levels and stunted growth, pointing to an inhibition of glycine decarboxylase (GDC). To reveal whether it is possible to suppress this marked phenotype, we exploited the power of a forward genetic screen. Absence of a so far uncharacterized member of the HaloAcid Dehalogenase (HAD)-like hydrolase family strongly suppressed the dwarf phenotype of er-ant1 plants. Localization studies suggested that the corresponding protein locates to chloroplasts, and activity assays showed that the enzyme dephosphorylates, with high substrate affinity, the B6 vitamer pyridoxal 5'-phosphate (PLP). Additional physiological experiments identified imbalances in vitamin B6 homeostasis in er-ant1 mutants. Our data suggest that impaired chloroplast metabolism, but not decreased GDC activity, causes the er-ant1 mutant dwarf phenotype. We present a hypothesis, setting transport of PLP by ER-ANT1 and chloroplastic PLP dephosphorylation in the cellular context. With the identification of this HAD-type PLP phosphatase, we also provide insight into B6 vitamer homeostasis.

Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells.

The cAMP-dependent aquaporin-2 (AQP2) redistribution from intracellular vesicles into the plasma membrane of renal collecting duct principal cells induces water reabsorption and fine-tunes body water homeostasis. However, the mechanisms controlling the localization of AQP2 are not understood in detail. Using immortalized mouse medullary collecting duct (MCD4) and primary rat inner medullary collecting duct (IMCD) cells as model systems, we here discovered a key regulatory role of Aurora kinase A (AURKA) in the control of AQP2. The AURKA-selective inhibitor Aurora-A inhibitor I and novel derivatives as well as a structurally different inhibitor, Alisertib, prevented the cAMP-induced redistribution of AQP2. Aurora-A inhibitor I led to a depolymerization of actin stress fibers, which serve as tracks for the translocation of AQP2-bearing vesicles to the plasma membrane. The phosphorylation of cofilin-1 (CFL1) inactivates the actin-depolymerizing function of CFL1. Aurora-A inhibitor I decreased the CFL1 phosphorylation, accounting for the removal of the actin stress fibers and the inhibition of the redistribution of AQP2. Surprisingly, Alisertib caused an increase in actin stress fibers and did not affect CFL1 phosphorylation, indicating that AURKA exerts its control over AQP2 through different mechanisms. An involvement of AURKA and CFL1 in the control of the localization of AQP2 was hitherto unknown.

Identification of disease-relevant modulators of the SHH pathway in the developing brain.

Pathogenic gene variants in humans that affect the sonic hedgehog (SHH) pathway lead to severe brain malformations with variable penetrance due to unknown modifier genes. To identify such modifiers, we established novel congenic mouse models. LRP2-deficient C57BL/6N mice suffer from heart outflow tract defects and holoprosencephaly caused by impaired SHH activity. These defects are fully rescued on a FVB/N background, indicating a strong influence of modifier genes. Applying comparative transcriptomics, we identified Pttg1 and Ulk4 as candidate modifiers upregulated in the rescue strain. Functional analyses showed that ULK4 and PTTG1, both microtubule-associated proteins, are positive regulators of SHH signaling, rendering the pathway more resilient to disturbances. In addition, we characterized ULK4 and PTTG1 as previously unidentified components of primary cilia in the neuroepithelium. The identification of genes that powerfully modulate the penetrance of genetic disturbances affecting the brain and heart is likely relevant to understanding the variability in human congenital disorders.

Metabolic Dynamics in Short- and Long-Term Microgravity in Human Primary Macrophages.

Microgravity acts on cellular systems on several levels. Cells of the immune system especially react rapidly to changes in gravity. In this study, we performed a correlative metabolomics analysis on short-term and long-term microgravity effects on primary human macrophages. We could detect an increased amino acid concentration after five minutes of altered gravity, that was inverted after 11 days of microgravity. The amino acids that reacted the most to changes in gravity were tightly clustered. The observed effects indicated protein degradation processes in microgravity. Further, glucogenic and ketogenic amino acids were further degraded to Glucose and Ketoleucine. The latter is robustly accumulated in short-term and long-term microgravity but not in hypergravity. We detected highly dynamic and also robust adaptative metabolic changes in altered gravity. Metabolomic studies could contribute significantly to the understanding of gravity-induced integrative effects in human cells.

Optimization of a Screening Hit toward M2912, an Oral Tankyrase Inhibitor with Antitumor Activity in Colorectal Cancer Models.

Constitutive activation of the canonical Wnt signaling pathway, in most cases driven by inactivation of the tumor suppressor APC, is a hallmark of colorectal cancer. Tankyrases are druggable key regulators in these malignancies and are considered as attractive targets for therapeutic interventions, although no inhibitor has been progressed to clinical development yet. We continued our efforts to develop tankyrase inhibitors targeting the nicotinamide pocket with suitable drug-like properties for investigating effects of Wnt pathway inhibition on tumor growth. Herein, the identification of a screening hit series and its optimization through scaffold hopping and SAR exploration is described. The systematic assessment delivered M2912, a compound with an optimal balance between excellent TNKS potency, exquisite PARP selectivity, and a predicted human PK compatible with once daily oral dosing. Modulation of cellular Wnt pathway activity and significant tumor growth inhibition was demonstrated with this compound in colorectal xenograft models in vivo.

Molecular and Spectroscopic Characterization of Green and Red Cyanine Fluorophores from the Alexa Fluor and AF Series*.

The use of fluorescence techniques has an enormous impact on various research fields including imaging, biochemical assays, DNA-sequencing and medical technologies. This has been facilitated by the development of numerous commercial dyes with optimized photophysical and chemical properties. Often, however, information about the chemical structures of dyes and the attached linkers used for bioconjugation remain a well-kept secret. This can lead to problems for research applications where knowledge of the dye structure is necessary to predict or understand (unwanted) dye-target interactions, or to establish structural models of the dye-target complex. Using a combination of optical spectroscopy, mass spectrometry, NMR spectroscopy and molecular dynamics simulations, we here investigate the molecular structures and spectroscopic properties of dyes from the Alexa Fluor (Alexa Fluor 555 and 647) and AF series (AF555, AF647, AFD647). Based on available data and published structures of the AF and Cy dyes, we propose a structure for Alexa Fluor 555 and refine that of AF555. We also resolve conflicting reports on the linker composition of Alexa Fluor 647 maleimide. We also conducted a comprehensive comparison between Alexa Fluor and AF dyes by continuous-wave absorption and emission spectroscopy, quantum yield determination, fluorescence lifetime and anisotropy spectroscopy of free and protein-attached dyes. All these data support the idea that Alexa Fluor and AF dyes have a cyanine core and are a derivative of Cy3 and Cy5. In addition, we compared Alexa Fluor 555 and Alexa Fluor 647 to their structural homologs AF555 and AF(D)647 in single-molecule FRET applications. Both pairs showed excellent performance in solution-based smFRET experiments using alternating laser excitation. Minor differences in apparent dye-protein interactions were investigated by molecular dynamics simulations. Our findings clearly demonstrate that the AF-fluorophores are an attractive alternative to Alexa- and Cy-dyes in smFRET studies or other fluorescence applications.

Inactivation of cytosolic FUMARASE2 enhances growth and photosynthesis under simultaneous copper and iron deprivation in Arabidopsis.

Copper (Cu) and iron (Fe) are essential for plant growth and are often in short supply under natural conditions. Molecular responses to simultaneous lack of both metals (-Cu-Fe) differ from those seen in the absence of either alone. Metabolome profiling of plant leaves previously revealed that fumarate levels fall under -Cu-Fe conditions. We employed lines lacking cytosolic FUMARASE2 (FUM2) activity to study the impact of constitutive suppression of cytosolic fumarate synthesis on plant growth under Cu and/or Fe deficiency. In fum2 mutants, photosynthesis and growth were less impaired under -Cu-Fe conditions than in wild-type (WT) seedlings. In particular, levels of photosynthetic proteins, chloroplast ultrastructure, amino acid profiles and redox state were less perturbed by simultaneous Cu-Fe deficiency in lines that cannot produce fumarate in the cytosol. Although cytosolic fumarate has been reported to promote acclimation of photosynthesis to low temperatures when metal supplies are adequate, the photosynthetic efficiency of fum2 lines grown under Cu-Fe deficiency in the cold was higher than in WT. Uptake and contents of Cu and Fe are similar in WT and fum2 plants under control and -Cu-Fe conditions, and lack of FUM2 does not alter the ability to sense metal deficiency, as indicated by marker gene expression. Collectively, we propose that reduced levels of cytosolic fumarate synthesis ultimately increase the availability of Fe for incorporation into metalloproteins.

Photocaged Hoechst Enables Subnuclear Visualization and Cell Selective Staining of DNA in vivo.

Selective targeting of DNA by means of fluorescent labeling has become a mainstay in the life sciences. While genetic engineering serves as a powerful technique and allows the visualization of nucleic acid by using DNA-targeting fluorescent fusion proteins in a cell-type- and subcellular-specific manner, it relies on the introduction of foreign genes. On the other hand, DNA-binding small fluorescent molecules can be used without genetic engineering, but they are not spatially restricted. Herein, we report a photocaged version of the DNA dye Hoechst33342 (pcHoechst), which can be uncaged by using UV to blue light for the selective staining of chromosomal DNA in subnuclear regions of live cells. Expanding its application to a vertebrate model organism, we demonstrate uncaging in epithelial cells and short-term cell tracking in vivo in zebrafish. We envision pcHoechst as a valuable tool for targeting and interrogating DNA with precise spatiotemporal resolution in living cells and wild-type organisms.

Systems biology of responses to simultaneous copper and iron deficiency in Arabidopsis.

Plant responses to coincident nutrient deficiencies cannot be predicted from the responses to individual deficiencies. Although copper (Cu) and iron (Fe) are essential micronutrients for plant growth that are often and concurrently limited in soils, the combinatorial response to Cu-Fe deficiency remains elusive. In the present study, we characterised the responses of Arabidopsis thaliana plants deprived of Cu, Fe or both (-Cu-Fe) at the level of plant development, mineral composition, and reconfiguration of transcriptomes, proteomes and metabolomes. Compared to single deficiencies, simultaneous -Cu-Fe leads to a distinct pattern in leaf physiology and microelement concentration characterised by lowered protein content and enhanced manganese and zinc levels. Conditional networking analysis of molecular changes indicates that biological processes also display different co-expression patterns among single and double deficiencies. Indeed, the interaction between Cu and Fe deficiencies causes distinct expression profiles for 15% of all biomolecules, leading to specific enhancement of general stress responses and protein homeostasis mechanisms, at the same time as severely arresting photosynthesis. Accordingly, central carbon metabolites, in particular photosynthates, decrease especially under -Cu-Fe conditions, whereas the pool of free amino acids increases. Further meta-analysis of transcriptomes and proteomes corroborated that protein biosynthesis and folding capacity were readjusted during the combinatorial response and unveiled important rearrangements in the metabolism of organic acids. Consequently, our results demonstrate that the response to -Cu-Fe imposes a distinct reconfiguration of large sets of molecules, not triggered by single deficiencies, resulting into a switch from autotrophy to heterotrophy and involving organic acids such as fumaric acid as central mediators of the response.

Antioxidant and anti-inflammatory properties of sourdoughs containing selected Lactobacilli strains are retained in breads.

Sourdough fermentation influences several properties of leavened baked goods also because Lactic acid bacteria (LAB) and yeasts produce bioactive peptides with a positive effect on human health. In an early study, three Lactobacilli strains (L. farciminis H3 and A11 and L. sanfranciscensis I4) possessing different proteolytic activities were used to produce sourdoughs containing peptides equipped with anti-inflammatory and/or antioxidant properties. This work was aimed to assess whether these properties could be retained after cooking. The selected LABs were used to produce breads from which low molecular weight (LMW-) peptides were extracted. The results provide solid proofs of keeping both antioxidant and anti-inflammatory activities of peptides from cooked products. Sequences of LMW-peptides either from doughs and breads were determined by mass spectrometry: differences have been noticed in amino acidic composition and in sequences, however, all the strains produce peptides equipped with antioxidant and anti-inflammatory activities.

[The sensitivity and specificity of the Mini-Audio-Test (MAT) for different levels of hearing loss]. / Die Sensitivität und Spezifität des Mini-Audio-Tests (MAT) für unterschiedliche Hörverlustschwellen.

BACKGROUND: An untreated hearing impairment could have a severe influence on the morbidity. The Mini-Audio-Test (MAT) has been developed for early detecting of a relevant hearing loss. This follow-up investigation should determine the sensitivity, specificity, and the predictive values for a minimum-level of detected hearing loss of 25, 30, 35, and 40 dB, both, in one octave-frequency between 0.5 and 4 kHz and the average of hearing loss for these four frequencies. METHODS: This survey uses data which were collected in 2016 and 2017. 943 patients parted into two groups (aged 50 to 59 years and aged 60 years and more), were investigated using the MAT. Statistical analysis on the sensitivity, specificity, and predictive values in respect were done as proportions together with the 95 %-confidence interval by a logistic regression. RESULTS: The sensitivity of the MAT was increasing in both groups of age by increasing the minimum of to be detected hearing loss. The specificity was decreasing as well, but less. The positive predictive values were higher for the older age-group and are decreasing by increasing of the minimum of to be detected hearing loss. In general, the values using the averaged hearing loss are noticeably lower than for the single frequency detecting. The values for the negative predictive values were contrary. CONCLUSION: The results for persons aged 60 years and more are worse than for the younger. Therefore, a first screening on hearing loss starting at the age of 50 years seems to be recommended urgently. Only by this, a sufficient rehabilitation of the hearing loss could be done in time so that the negative consequences of an untreated hearing impairment could be influenced positively.

Super-Resolution Imaging of Tight and Adherens Junctions: Challenges and Open Questions.

The tight junction (TJ) and the adherens junction (AJ) bridge the paracellular cleft of epithelial and endothelial cells. In addition to their role as protective barriers against bacteria and their toxins they maintain ion homeostasis, cell polarity, and mechano-sensing. Their functional loss leads to pathological changes such as tissue inflammation, ion imbalance, and cancer. To better understand the consequences of such malfunctions, the junctional nanoarchitecture is of great importance since it remains so far largely unresolved, mainly because of major difficulties in dynamically imaging these structures at sufficient resolution and with molecular precision. The rapid development of super-resolution imaging techniques ranging from structured illumination microscopy (SIM), stimulated emission depletion (STED) microscopy, and single molecule localization microscopy (SMLM) has now enabled molecular imaging of biological specimens from cells to tissues with nanometer resolution. Here we summarize these techniques and their application to the dissection of the nanoscale molecular architecture of TJs and AJs. We propose that super-resolution imaging together with advances in genome engineering and functional analyses approaches will create a leap in our understanding of the composition, assembly, and function of TJs and AJs at the nanoscale and, thereby, enable a mechanistic understanding of their dysfunction in disease.

Redistribution of pulmonary ventilation after lung surgery detected with electrical impedance tomography.

BACKGROUND: Regional ventilation of the lung can be visualized by pulmonary electrical impedance tomography (EIT). The aim of this study was to examine the post-operative redistribution of regional ventilation after lung surgery dependent on the side of surgery and its association with forced vital capacity. METHODS: In this prospective, observational cohort study 13 patients undergoing right and 13 patients undergoing left-sided open or video-thoracoscopic procedures have been investigated. Pre-operative measurements with EIT and spirometry were compared with data obtained 3 days post-operation. The center of ventilation (COV) within a 32 × 32 pixel matrix was calculated from EIT data. The transverse axis coordinate of COV, COVx (left/right), was modified to COVx' (ipsilateral/contralateral). Thus, COVx' shows a negative change if ventilation shifts contralateral independent of the side of surgery. This enabled testing with two-way ANOVA for repeated measurements (side, time). RESULTS: The perioperative shift of COVx' was dependent on the side of surgery (P = .007). Ventilation shifted away from the side of surgery after the right-sided surgery (COVx'-1.97 pixel matrix points, P < .001), but not after the left-sided surgery (COVx'-0.61, P = .425). The forced vital capacity (%predicted) decreased from 94 (83-109)% (median [quartiles]; [left-sided]) and 89 (80-97)% (right-sided surgery) to 61 (59-66)% and 62 (40-72)% (P < .05), respectively. The perioperative changes in forced vital capacity (%predicted) were weakly associated with the shift of COVx'. CONCLUSION: Only after right-sided lung surgery, EIT showed reduced ventilation on the side of surgery while vital capacity was markedly reduced in both groups.

NTRC Plays a Crucial Role in Starch Metabolism, Redox Balance, and Tomato Fruit Growth.

NADPH-thioredoxin reductase C (NTRC) forms a separate thiol-reduction cascade in plastids, combining both NADPH-thioredoxin reductase and thioredoxin activities on a single polypeptide. While NTRC is an important regulator of photosynthetic processes in leaves, its function in heterotrophic tissues remains unclear. Here, we focus on the role of NTRC in developing tomato (Solanum lycopersicum) fruits representing heterotrophic storage organs important for agriculture and human diet. We used a fruit-specific promoter to decrease NTRC expression by RNA interference in developing tomato fruits by 60% to 80% compared to the wild type. This led to a decrease in fruit growth, resulting in smaller and lighter fully ripe fruits containing less dry matter and more water. In immature fruits, NTRC downregulation decreased transient starch accumulation, which led to a subsequent decrease in soluble sugars in ripe fruits. The inhibition of starch synthesis was associated with a decrease in the redox-activation state of ADP-Glc pyrophosphorylase and soluble starch synthase, which catalyze the first committed and final polymerizing steps, respectively, of starch biosynthesis. This was accompanied by a decrease in the level of ADP-Glc. NTRC downregulation also led to a strong increase in the reductive states of NAD(H) and NADP(H) redox systems. Metabolite profiling of NTRC-RNA interference lines revealed increased organic and amino acid levels, but reduced sugar levels, implying that NTRC regulates the osmotic balance of developing fruits. These results indicate that NTRC acts as a central hub in regulating carbon metabolism and redox balance in heterotrophic tomato fruits, affecting fruit development as well as final fruit size and quality.