The value of sonographic microvascular imaging in the diagnosis of lipedema.

BACKGROUND: Lipedema is a chronic disease marked by symmetric enlargement of painful nodular and fibrotic adipose tissue, predominantly affecting the limbs. Since there is no specific test or biomarker for this condition, years often pass before the diagnosis of lipedema is established for the first time, thereby causing psychosocial distress, including depression, eating disorders, and social isolation. Over the last few years several advanced Doppler-based technologies have been developed to visualize slow flow blood vessels and superficial microvascular architecture undetectable by traditional color Doppler flow imaging (CDFI). OBJECTIVE: The aim of this study was to evaluate the superficial microvascular anatomy in lipedema patients compared to healthy controls and investigate the clinical significance of the Ultra Micro Angiography (UMA) technology in the diagnosis of lipedema. This new technique may contribute to reduce the diagnostic delay and, eventually, establish and guide treatment strategies toward a better therapeutic outcome in lipedema patients. METHODS: 25 patients with lipedema and ten healthy controls with no history of lipedema were included in this study. All ultrasound examinations were performed on a novel high-performance ultrasound system (Resona R9/Mindray) using CDFI and the UMA technique. RESULTS: In all of the patients, Ultra Micro Angiography achieved the excellent visualization of microvascular structures, revealing that most lipedema patients showed grade 3 (n = 13) or grade 2 (n = 8) flow. UMA was superior to CDFI for depicting the microvascular structures. CONCLUSIONS: Here we show that UMA imaging characterizes the subcutaneous microvasculature with an unprecedented accuracy. The method has the advantage of being sensitive to small, slow-flowing vessels. This allows for the assessment of the course of vessels and vascular pathologies in great detail. Thus, UMA as a non-invasive diagnostic method can improve diagnostic accuracy in lipedema.

Biocompatibility of polyurethane-coated breast implants: A histological comparison of implant capsules.

BACKGROUND: Biocompatibility describes the influence of materials on their biological environment. Implant material in the human body can cause a foreign body reaction and the formation of a capsule around the foreign material. Since capsular formation is the most frequent issue after breast-implant insertion, knowledge and awareness of biocompatibility is crucial, especially since worldwide, breast augmentation continues to be the most popular plastic surgery, with over 1.6 million procedures performed in 2020, according to surveys by the International Society of Aesthetic Plastic Surgery (ISAPS). MATERIAL AND METHODS: This study includes 80 capsular samples of female patients who underwent revision surgery after breast-implant insertion at the University Hospital Regensburg. Capsules of breast implants with different surface structures (smooth, textured and polyurethane-coated) and shapes (round-shaped, anatomically-shaped) were analyzed histologically after hematoxylin-eosin-staining in respect to capsular thickness and layer formation. RESULTS: Capsular thickness and layering showed a statistically significant difference between polyurethane-coated and smooth as well as polyurethane-coated and textured implants. Capsules around polyurethane-coated implants presented greater thickness. However, the difference between smooth and textured implants was not statistically significant. Furthermore, the shape of the implants also indicated a statistically significant difference in capsular thickness. Implants of anatomical shape resulted in a thinner capsule than round-shaped breast-implants. CONCLUSION: In conclusion, this study demonstrated a thicker capsule around polyurethane-coated breast implants and no difference in capsular thickness between smooth and textured breast implants. Anatomically shaped breast-implants presented a thinner capsule than round shaped breast-implants.

Author Correction: Proteomic and Transcriptomic Changes in Hibernating Grizzly Bears Reveal Metabolic and Signaling Pathways that Protect against Muscle Atrophy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Proteomic and Transcriptomic Changes in Hibernating Grizzly Bears Reveal Metabolic and Signaling Pathways that Protect against Muscle Atrophy.

Muscle atrophy is a physiological response to disuse and malnutrition, but hibernating bears are largely resistant to this phenomenon. Unlike other mammals, they efficiently reabsorb amino acids from urine, periodically activate muscle contraction, and their adipocytes differentially responds to insulin. The contribution of myocytes to the reduced atrophy remains largely unknown. Here we show how metabolism and atrophy signaling are regulated in skeletal muscle of hibernating grizzly bear. Metabolic modeling of proteomic changes suggests an autonomous increase of non-essential amino acids (NEAA) in muscle and treatment of differentiated myoblasts with NEAA is sufficient to induce hypertrophy. Our comparison of gene expression in hibernation versus muscle atrophy identified several genes differentially regulated during hibernation, including Pdk4 and Serpinf1. Their trophic effects extend to myoblasts from non-hibernating species (including C. elegans), as documented by a knockdown approach. Together, these changes reflect evolutionary favored adaptations that, once translated to the clinics, could help improve atrophy treatment.

Transforming nursing care through health literacy ACTS.

Limited patient literacy contributes to poorer health status, increased emergency room and hospital use, higher morbidity and mortality rates, and less use of preventive health services. All patients, however, need health information that is accurate, accessible, and actionable to make informed decisions about their health. A universal health literacy precautions approach is recommended to empower patients through shared decision-making interactions. Consistent use of evidence-based health literacy practices by front-line nurses offers the potential for transformations in nursing care through stronger patient-nurse interactions and health system partnerships.

The growing complexity of HIF-1α's role in tumorigenesis: DNA repair and beyond.

Lack of oxygen (hypoxia) is a central hallmark of cancer and a pivotal driving force of malignant progression. Transcriptional activators of the hypoxia-inducible factor α (HIFα) family represent the principal molecular mediators of hypoxia under both physiological and pathophysiological conditions. While HIF-2α is expressed in a tissue- and cell-type-restricted manner, stabilization of HIF-1α was reported in tumours of widely different origin, and functional analyses led to the perception of HIF-1α as an oncoprotein. In this review, we aim to acknowledge HIFα's growing complexity by outlining its functional relevance for genomic integrity and tumour heterogeneity, two features of paramount importance for basic and clinical oncology. Pharmaceutical companies around the globe are ambitiously hunting for HIF-1α-inhibiting compounds, some of which are currently being evaluated in phase 1 trials. To avoid the rather disappointing clinical efficacy emblematic of most targeted therapeutics, potential resistance mechanisms of, as well as potential combination partners for, HIF-1α-inhibiting drugs should be evaluated. In this regard, the interrelation of HIF-1α with genomic integrity and tumour heterogeneity offers ample possibilities, potentially resulting in more efficient clinical translation of HIF-1α's pathobiology.

Effect of sulfur availability on the integrity of amino acid biosynthesis in plants.

Amino acid levels in plants are regulated by a complex interplay of regulatory circuits at the level of enzyme activities and gene expression. Despite the diversity of precursors involved in amino acid biosynthesis as providing the carbon backbones, the amino groups and, for the amino acids methionine and cysteine, the sulfhydryl group and despite the involvement of amino acids as substrates in various downstream metabolic processes, the plant usually manages to provide relatively constant levels of all amino acids. Here we collate data on how amino acid homeostasis is shifted upon depletion of one of the major biosynthetic constituents, i.e., sulfur. Arabidopsis thaliana seedlings exposed to sulfate starvation respond with a set of adaptation processes to achieve a new balance of amino acid metabolism. First, metabolites containing reduced sulfur (cysteine, glutathione, S-adenosylmethionine) are reduced leading to a number of downstream effects. Second, the relative excess accumulation of N over S triggers processes to dump nitrogen in asparagine, glutamine and further N-rich compounds like ureides. Third, the depletion of glutathione affects the redox and stress response system of the glutathione-ascorbate cycle. Thus, biosynthesis of aromatic compounds is triggered to compensate for this loss, leading to an increased flux and accumulation of aromatic amino acids, especially tryptophan. Despite sulfate starvation, the homeostasis is kept, though shifted to a new state. This adaptation process keeps the plant viable even under an adverse nutritional status.

Engineering of cysteine and methionine biosynthesis in potato.

Methionine and cysteine, two amino acids containing reduced sulfur, are not only an important substrate of protein biosynthesis but are also precursors of various other metabolites such as glutathione, phytochelatines, S-adenosylmethionine, ethylene, polyamines, biotin, and are involved as methyl group donor in numerous cellular processes. While methionine is an essential amino acid due to an inability of monogastric animals and human beings to synthesise this metabolite, animals are still able to convert methionine consumed with their diet into cysteine. Thus, a balanced diet containing both amino acids is necessary to provide a nutritionally favourable food or feed source. Because the concentrations of methionine and cysteine are often low in edible plant sources, e.g. potato, considerable efforts in plant breeding and research have been and are still performed to understand the physiological, biochemical, and molecular mechanisms that contribute to their synthesis, transport, and accumulation in plants. During the last decade molecular tools have enabled the isolation of most of the genes involved in cysteine and methionine biosynthesis, and the efficient plant transformation technology has allowed the creation of transgenic plants that are altered in the activity of individual genes. The physiological analysis of these transgenic plants has contributed considerably to our current understanding of how amino acids are synthesised. We focused our analysis on potato (Solanum tuberosum cv. Désirée) as this plant provides a clear separation of source and sink tissues and, for applied purposes, already constitutes a crop plant. From the data presented here and in previous work we conclude that threonine synthase and not cystathionine gamma-synthase as expected from studies of Arabidopsis constitutes the main regulatory control point of methionine synthesis in potato. This article aims to cover the current knowledge in the area of molecular genetics of sulfur-containing amino acid biosynthesis and will provide new data for methionine biosynthesis in solanaceous plants such as potato.

Indications for a novel muscular dystrophy pathway. gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin.

gamma-Filamin, also called ABP-L, is a filamin isoform that is specifically expressed in striated muscles, where it is predominantly localized in myofibrillar Z-discs. A minor fraction of the protein shows subsarcolemmal localization. Although gamma-filamin has the same overall structure as the two other known isoforms, it is the only isoform that carries a unique insertion in its immunoglobulin (Ig)-like domain 20. Sequencing of the genomic region encoding this part of the molecule shows that this insert is encoded by an extra exon. Transient transfections of the insert-bearing domain in skeletal muscle cells and cardiomyocytes show that this single domain is sufficient for targeting to developing and mature Z-discs. The yeast two-hybrid method was used to identify possible binding partners for the insert-bearing Ig-like domain 20 of gamma-filamin. The two Ig-like domains of the recently described alpha-actinin-binding Z-disc protein myotilin were found to interact directly with this filamin domain, indicating that the amino-terminal end of gamma-filamin may be indirectly anchored to alpha-actinin in the Z-disc via myotilin. Since defects in the myotilin gene were recently reported to cause a form of autosomal dominant limb-girdle muscular dystrophy, our findings provide a further contribution to the molecular understanding of this disease.

[The use of lymphocyte cultures for the investigation of drug biotransformation]. / Die Verwendung von Lymphozytenkulturen für Untersuchungen zur Biotransformation von Arzneistoffen.

In the present paper the rat lymphocytes and mouse myeloma cell culture are developed as in vitro test systems and used for the investigation on the biotransformation of drugs. The rat lymphocyte culture was established as a suspension culture after the isolation of the cells from the spleen of male wistar rats by mechanical disaggregation and density gradient centrifugation with a yield of 10(7) cells per spleen and a viability of 80%. The addition of the mitogens PHA and Con A to the culture stimulated the proliferation of the lymphocytes leading to a doubling of the number of cells comparing with control cultures. Myeloma cells are a permanent cell line of B-lymphocytes. The cultivation was carried out as stationary suspension. The marked proliferation of the cells could be increased by addition of Con A. The biochemical properties of both kinds of cells are qualitatively comparable. Cytochrome P-450 mediated demethylase activities could be detected, which were 5-10 fold higher in myeloma cells. The pretreatment with the enzyme inductors phenobarbitone and 3-methylcholanthrene as well as the addition of the mitogens PHA and Con A increased these turnover rates. Reductive and conjugating activities were not present in the cultures. The established and characterized in vitro systems were applied for the investigation on the biotransformation of 4 potential drugs. The cardiac effective Trapidil (Rocornal) derivative AR 12463 (5-piperidino-7-[N-pentyl-N-(beta-hydroxyethyl)]- amino-s-triazolo[1,5-a]pyrimidine) is transformed in lymphocyte and myeloma cell cultures in two compounds. These substances revealed as the hydroxypentyl- and the hydroxypyrimidine derivative.(ABSTRACT TRUNCATED AT 250 WORDS)

[The biotransformation of the immunostimulant 3-(2-mercaptoethyl)quinazoline-2,4(1H,3H)-dione (AWD 100-041)]. / Untersuchungen zur Biotransformation des Immunstimulans 3-(2-Mercaptoethyl)chinazolin-2,4(1 H,3 H)-dion (AWD 100-041).

3-(2-Mercaptoethyl)quinazoline-2,4(1 H,3 H)-dione (1; AWD 100-041) is a substance with immunomodulating and immunorestorative activity. After p.o. administration in male Wistar rats at least 7 metabolites are formed and excreted in urine and faeces. The compounds were isolated and identified on the basis of UV and mass spectra. They are S-methylated structures in which sulfoxidation and ring-hydroxylation have been taken place. Four metabolites are also present as sulfate or glucuronide conjugates. The quantity ratio of the phase I to phase II metabolites amounts to 4:1. In the isolated perfused rat liver and rat hepatocyte culture 6 and 5 of the in vivo identified compounds are formed. The sequence of the metabolic pathways could be confirmed by in vitro experiments in which the incubation of synthetically prepared metabolites and the identification of generated biotransformation products were performed. In the lymphocyte and myeloma cell culture solely the disulfide of 1 is formed. After incubation of the S-methyl compound metabolites originate detectable also in vivo. Regarding the main ways of metabolism firstly 1 is attacked by methyltransferases forming the initial metabolite. After that oxidative processes take place leading to the formation of sulfoxides, sulfones as well as ring-hydroxylated compounds. A part of the ring-hydroxylated metabolites are conjugated.