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Abstract Recent research has identified growth differentiation factor 15 (GDF15) as a crucial factor in various physiological and pathological processes, particularly in energy balance regulation. While the role of GDF15 in modulating energy metabolism through hindbrain GDNF family receptor alpha-like (GFRAL) signaling has been extensively studied, emerging evidence suggests direct peripheral metabolic actions of GDF15. Using knockout mouse models, we investigated GDF15 and GFRAL’s roles in adipose tissue metabolism. Our findings indicate that C57BL/6/129/SvJ Gdf15-KO mice exhibit impaired expression of de novo lipogenesis enzymes in subcutaneous adipose tissue (sWAT). In contrast, C57BL/6J Gfral-KO mice showed no impairments compared to wild-type (WT) littermates. RNA-Seq analysis of sWAT in Gdf15-KO mice revealed a broad downregulation of genes involved in lipid metabolism. Importantly, our study uncovered sex-specific effects, with females being more affected by GDF15 loss than males. Additionally, we observed a fasting-induced upregulation of GDF15 gene expression in sWAT of both mice and humans, reinforcing this factor’s role in adipose tissue lipid metabolism. In conclusion, our research highlights an essential role for GDF15 in sWAT lipid metabolic homeostasis. These insights enhance our understanding of GDF15’s functions in adipose tissue physiology and underscore its potential as a therapeutic target for metabolic disorders.

Objective Guillain-Barre Syndrome (GBS) is a rare acute inflammatory demyelinating polyneuropathy, resulting in loss of muscle function and potentially respiratory failure requiring prolonged mechanical ventilation. Data describing the demographics and outcomes of patients with severe GBS requiring prolonged ventilation in the long-term acute care hospital (LTACH) setting is limited. We hypothesized that patients with GBS requiring prolonged mechanical ventilation require longer lengths of stay in an LTACH and are discharged with poorer functional status than GBS patients who do not require mechanical ventilation. Design, Setting, and Participants We conducted a retrospective study of GBS patients admitted over a 9-year period at an independent, large LTACH and compared ventilated versus non-ventilated GBS patients’ lengths of stay and functional ability at the time of admission and discharge. Interventions Not Applicable Main Outcome Measures and Results We found no significant difference in mean (standard error of means) lengths of stay between ventilated and non-ventilated GBS patients admitted to an LTACH (48.4 (± 8.0) vs. 38.8 (± 5.7) days, P 0.37). We also found that ventilated patients with GBS were discharged from an LTACH with similar functional ability than non-ventilated GBS patients (4.5 vs. 4.0, P 0.43 on 10 ft walk; 4.7 vs. 4.5 on P 0.70; 5.0 vs. 4.2, P 0.21 on 150 ft walk). Conclusion These findings suggest that GBS patients suffering from prolonged mechanical ventilation may expect similar lengths of stay in an LTACH as non-ventilated GBS patients and a similar or greater rate of functional improvement during their stay. These data support admission of chronically ventilated GBS patients to an LTACH for ongoing care after their acute care without the anticipation of greater length of stay or less rehabilitation outcomes with respect to non-ventilated GBS patients.

Introduction Tracheostomy is a necessary procedure required for prolonged mechanical ventilation in long-term acute care hospitals (LTACH). Many factors influence successful decannulation, or tracheostomy removal, and it is unclear what factors are essential for determining decannulation. The purpose of this study was to determine retrospective performance of single prognostic variables for successful decannulation, like peak expiratory flow measurement, overnight oximetry testing, and blood gas analysis. Methods A retrospective analysis of a three-year period to investigate the association between peak flow (PF) measurements ≥160 L/min, successful overnight oximetry (ONO), sex, and decannulation success. Average PF measurements, arterial blood gas (ABG), days on mechanical ventilation, LTACH length of stay (LOS), and age were also investigated. Results We examined the records of 135 patients, 127 of which were successfully decannulated. PF measurements ≥160 L/min (P 0.16), sex (P 0.05). Conclusions These results suggest no single prognostic variable can predict decannulation outcomes. Rather, clinical judgment of experienced medical professionals appears sufficient to achieve a 94% decannulation success rate. Additional investigation is required to determine what metrics are necessary, or if clinical judgment alone can predict decannulation success.

Acidobacteria occur in a large variety of ecosystems worldwide and are particularly abundant and highly diverse in soils. In spite of their diversity, only few species have been characterized to date which makes Acidobacteria one of the most poorly understood phyla among the domain Bacteria. We used a culture-independent niche modeling approach to elucidate ecological adaptations and their evolution for 4,154 operational taxonomic units (OTUs) of Acidobacteria across 150 different, comprehensively characterized grassland soils in Germany. Using the relative abundances of their 16S rRNA gene transcripts, the responses of active OTUs along gradients of 41 environmental variables were modeled using hierarchical logistic regression (HOF), which allowed to determine values for optimum activity for each variable (niche optima). By linking 16S rRNA transcripts to the phylogeny of full 16S rRNA gene sequences, we could trace the evolution of the different ecological adaptations during the diversification of Acidobacteria. This approach revealed a pronounced ecological diversification even among acidobacterial sister clades. Although the evolution of habitat adaptation was mainly cladogenic, it was disrupted by recurrent events of convergent evolution that resulted in frequent habitat switching within individual clades. Our findings indicate that the high diversity of soil acidobacterial communities is largely sustained by differential habitat adaptation even at the level of closely related species. A comparison of niche optima of individual OTUs with the phenotypic properties of their cultivated representatives showed that our niche modeling approach (1) correctly predicts those physiological properties that have been determined for cultivated species of Acidobacteria but (2) also provides ample information on ecological adaptations that cannot be inferred from standard taxonomic descriptions of bacterial isolates. These novel information on specific adaptations of not-yet-cultivated Acidobacteria can therefore guide future cultivation trials and likely will increase their cultivation success.