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Purpose: Given the increased cardio-metabolic risk in patients with acromegaly, this study compared cardiovascular outcomes, mortality, and in-hospital outcomes between patients with acromegaly and non-functioning pituitary adenoma (NFPA) following pituitary surgery., Methods: This was a nationwide cohort study using data from hospitalized patients with acromegaly or NFPA undergoing pituitary surgery in Switzerland between January 2012 and December 2021. Using 1:3 propensity score matching, eligible acromegaly patients were paired with NFPA patients who underwent pituitary surgery, respectively. The primary outcome comprised a composite of cardiovascular events (myocardial infarction, cardiac arrest, ischemic stroke, hospitalization for heart failure, unstable angina pectoris, cardiac arrhythmias, intracranial hemorrhage, hospitalization for hypertensive crisis) and all-cause mortality. Secondary outcomes included individual components of the primary outcome, surgical re-operation, and various hospital-associated outcomes., Results: Among 231 propensity score-matched patients with acromegaly and 491 with NFPA, the incidence rate of the primary outcome was 8.18 versus 12.73 per 1,000 person-years (hazard ratio [HR], 0.64; [95% confidence interval [CI], 0.31-1.32]). Mortality rates were numerically lower in acromegaly patients (2.43 vs. 7.05 deaths per 1,000 person-years; HR, 0.34; [95% CI, 0.10-1.17]). Individual components of the primary outcome and in-hospital outcomes showed no significant differences between the groups., Conclusion: This cohort study did not find an increased risk of cardiovascular outcomes and mortality in patients with acromegaly undergoing pituitary surgery compared to surgically treated NFPA patients. These findings suggest that there is no legacy effect regarding higher cardio-metabolic risk in individuals with acromegaly once they receive surgical treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Key Message: Phosphoglycerate Dehydrogenase 1 of the phosphorylated pathway of serine biosynthesis, active in heterotrophic plastids, is required for the synthesis of serine to enable plant growth at high rates of indolic glucosinolate biosynthesis. Plants have evolved effective strategies to defend against various types of pathogens. The synthesis of a multitude of specialized metabolites represents one effective approach to keep plant attackers in check. The synthesis of those defense compounds is cost intensive and requires extensive interaction with primary metabolism. However, how primary metabolism is adjusted to fulfill the requirements of specialized metabolism is still not completely resolved. Here, we studied the role of the phosphorylated pathway of serine biosynthesis (PPSB) for the synthesis of glucosinolates, the main class of defensive compounds in the model plant Arabidopsis thaliana. We show that major genes of the PPSB are co-expressed with genes required for the synthesis of tryptophan, the unique precursor for the formation of indolic glucosinolates (IG). Transcriptional and metabolic characterization of loss-of-function and dominant mutants of ALTERED TRYPTOPHAN1-like transcription factors revealed demand driven activation of PPSB genes by major regulators of IG biosynthesis. Trans-activation of PPSB promoters by ATR1/MYB34 transcription factor in cultured root cells confirmed this finding. The content of IGs were significantly reduced in plants compromised in the PPSB and these plants showed higher sensitivity against treatment with 5-methyl-tryptophan, a characteristic behavior of mutants impaired in IG biosynthesis. We further found that serine produced by the PPSB is required to enable plant growth under conditions of high demand for IG. In addition, PPSB-deficient plants lack the growth promoting effect resulting from interaction with the beneficial root-colonizing fungus Colletotrichum tofieldiae., (© 2021. The Author(s).)

Because it is the precursor for various essential cellular components, the amino acid serine is indispensable for every living organism. In plants, serine is synthesized by two major pathways: photorespiration and the phosphorylated pathway of serine biosynthesis (PPSB). However, the importance of these pathways in providing serine for plant development is not fully understood. In this study, we examine the relative contributions of photorespiration and PPSB to providing serine for growth and metabolism in the C3 model plant Arabidopsis thaliana. Our analyses of cell proliferation and elongation reveal that PPSB-derived serine is indispensable for plant growth and its loss cannot be compensated by photorespiratory serine biosynthesis. Using isotope labeling, we show that PPSB-deficiency impairs the synthesis of proteins and purine nucleotides in plants. Furthermore, deficiency in PPSB-mediated serine biosynthesis leads to a strong accumulation of metabolites related to nitrogen metabolism. This result corroborates 15N-isotope labeling in which we observed an increased enrichment in labeled amino acids in PPSB-deficient plants. Expression studies indicate that elevated ammonium uptake and higher glutamine synthetase/glutamine oxoglutarate aminotransferase (GS/GOGAT) activity causes this phenotype. Metabolic analyses further show that elevated nitrogen assimilation and reduced amino acid turnover into proteins and nucleotides are the most likely driving forces for changes in respiratory metabolism and amino acid catabolism in PPSB-deficient plants. Accordingly, we conclude that even though photorespiration generates high amounts of serine in plants, PPSB-derived serine is more important for plant growth and its deficiency triggers the induction of nitrogen assimilation, most likely as an amino acid starvation response., (© American Society of Plant Biologists 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

During photosynthesis, electrons travel from light-excited chlorophyll molecules along the electron transport chain to the final electron acceptor nicotinamide adenine dinucleotide phosphate (NADP) to form NADPH, which fuels the Calvin-Benson-Bassham cycle (CBBC). To allow photosynthetic reactions to occur flawlessly, a constant resupply of the acceptor NADP is mandatory. Several known stromal mechanisms aid in balancing the redox poise, but none of them utilizes the structurally highly similar coenzyme NAD(H). Using Arabidopsis (Arabidopsis thaliana) as a C3-model, we describe a pathway that employs the stromal enzyme PHOSPHOGLYCERATE DEHYDROGENASE 3 (PGDH3). We showed that PGDH3 exerts high NAD(H)-specificity and is active in photosynthesizing chloroplasts. PGDH3 withdrew its substrate 3-PGA directly from the CBBC. As a result, electrons become diverted from NADPH via the CBBC into the separate NADH redox pool. pgdh3 loss-of-function mutants revealed an overreduced NADP(H) redox pool but a more oxidized plastid NAD(H) pool compared to wild-type plants. As a result, photosystem I acceptor side limitation increased in pgdh3. Furthermore, pgdh3 plants displayed delayed CBBC activation, changes in nonphotochemical quenching, and altered proton motive force partitioning. Our fluctuating light-stress phenotyping data showed progressing photosystem II damage in pgdh3 mutants, emphasizing the significance of PGDH3 for plant performance under natural light environments. In summary, this study reveals an NAD(H)-specific mechanism in the stroma that aids in balancing the chloroplast redox poise. Consequently, the stromal NAD(H) pool may provide a promising target to manipulate plant photosynthesis., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Eleven children with cerebral palsy were studied after shelf acetabular augmentation for progressive hip subluxation. Evaluation was based on computed tomography (CT) scans and radiographic measurements. We noted significant improvement in subluxation as measured by migration percentage, without increased subluxation of the nonoperated hip. Preoperatively, our patients had anterior acetabular deficiencies and increased acetabular anteversion, but no posterior deficiency by CT scanning. The acetabular shelves were positioned relatively more anteriorly than posteriorly. This appears to be appropriate owing to the relative anterior deficiencies of the acetabuli in our patients.