Ligaclip for Preauricular Skin Tags in the Newborn

Introduction Skin tags are benign lesions, that often represent only an aesthetic problem; if subjected to trauma, they can occasionally bleed with possible infection and pain. When they occur in the preauricular region, attention should be paid to the diagnosis and approach; in fact, controversy exists in the differential diagnosis between hair follicle nevi, accessory tragus, and skin tag. Misdiagnosis and failure of treatment can lead to serious consequences, such as chondritis. Materials and Methods In our retrospective study, we evaluated 19 newborns affected by single, unilateral skin tag in the preauricular region. Each patient underwent a careful clinical examination; lesions without a pilosebaceous unit and with a thin, soft pedicle were treated in the nursery with Ligaclip (Johnson & Johnson). Results Skin tag falls between day 7 and 10. We had no cases of edema, cellulitis, clip loss, or bleeding. Scarring results were extremely satisfactory at 3-month follow-up. Conclusion We believe that after a careful clinical examination, cases of skin tags in the preauricular area can be selected and treated with Ligaclip. This procedure can be considered rapid, safe, economical, and simple in the newborn patients

Diversity of dermal fibroblasts as major determinant of variability in cell reprogramming

Induced pluripotent stem cells (iPSCs) are adult somatic cells genetically reprogrammed to an embryonic stem cell-like state. Notwithstanding their autologous origin and their potential to differentiate towards cells of all three germ layers, iPSC reprogramming is still affected by low efficiency. As dermal fibroblast is the most used human cell for reprogramming, we hypothesize that the variability in reprogramming is, at least partially, because of the skin fibroblasts used. Human dermal fibroblasts harvested from five different anatomical sites (neck, breast, arm, abdomen and thigh) were cultured and their morphology, proliferation, apoptotic rate, ability to migrate, expression of mesenchymal or epithelial markers, differentiation potential and production of growth factors were evaluated in vitro. Additionally, gene expression analysis was performed by real-time PCR including genes typically expressed by mesenchymal cells. Finally, fibroblasts isolated from different anatomic sites were reprogrammed to iPSCs by integration-free method. Intriguingly, while the morphology of fibroblasts derived from different anatomic sites differed only slightly, other features, known to affect cell reprogramming, varied greatly and in accordance with anatomic site of origin. Accordingly, difference also emerged in fibroblasts readiness to respond to reprogramming and ability to form colonies. Therefore, as fibroblasts derived from different anatomic sites preserve positional memory, it is of great importance to accurately evaluate and select dermal fibroblast population prior to induce reprogramming

Porcine model for deep superior epigastric artery perforator flap harvesting: Anatomy and technique

BACKGROUND Microsurgical training on rats before starting with clinical practice is a well-established routine. Animal model training is less widespread for perforator flaps, although these flaps represent a technical challenge. Unlike other flaps, they require specific technical skills that need to be adequately trained on a living model 1 : a cadaver is not enough because no bleeding, vessel damage, or vasospasm can be simulated. 2 The purpose of this study was to assess the suitability of the porcine abdomen as a training model for the deep inferior epigastric artery perforator (DIEAP) flap, commonly used in human breast reconstruction. METHODS A female swine (Sus scrofa domesticus, ssp; weight 25kg) was used. The procedure was performed with the pig under general anesthesia and in the supine position. A deep superior epigastric artery perforator (DSEAP) flap was harvested on the left side of the abdomen, including the 3 cranial nipples and stopping in the midline to spare the contralateral flap for another dissection (as in bilateral breast reconstructions in humans; Fig. 1). All steps of a DIEAP harvest were simulated: superficial vein harvest, suprafascial perforator dissection, intramuscular perforator harvest with preservation of the nerves, and flap isolation. Observation of capillary refill was used to confirm flap viability at the end of the dissection. The procedure was recorded by means of a GoPro camera and simultaneously with a head mounted (4 7 magnification) Loupecam system. Photographs were taken using 2 cameras during surgery at relevant time points. RESULTS At the end of the dissection, the flap was viable. The subcutaneous adipose tissue of the pig is less represented than in human and pigs have an additional muscular layer, the panniculus carnosus, which is the analogue of the human Scarpa's fascia. The rectus fascia is thinner. The perforators are lined in 2 rows: 1 lateral and 1 medial, as in the DIEAP, and the intercostal nerves cross the vessels, as happens in humans. The porcine rectus abdominis muscle is thinner than the human one, but vessels' branching faithfully reproduces the human model. 1 We identified 5 perforating vessels of more than 1mm in diameter (2 lateral and 3 medial). We isolated a lateral perforator first and a medial one last: the latter was eventually used to nourish the flap (Fig. 2). CONCLUSIONS The DSEAP flap allows one to closely reproduce all the steps of DIEAP flap harvesting and also to carry out the intramuscular dissection of 2 perforators for each side (up to 4 for each animal), confirming the adequacy of this pig model for microsurgical training. The deep superior epigastric artery is dominant in pigs. 3 Despite this anatomical difference, the DSEAP allows one to reproduce the main steps of DIEAP flap harvesting, providing an excellent training model. Moreover, the presence of double perforating rows allows simulating the dissection twice on each side

A low-cost scalable 3D-printed sample-holder for agitation-based decellularization of biological tissues

Decellularized extracellular matrix is one of the most promising biological scaffold supporting in vitro tissue growth and in vivo tissue regeneration in both preclinical research and clinical practice. In case of thick tissues or even organs, conventional static decellularization methods based on chemical or enzymatic treatments are not effective in removing the native cellular material without affecting the extracellular matrix. To overcome this limitation, dynamic decellularization methods, mostly based on perfusion and agitation, have been proposed. In this study, we developed a low-cost scalable 3D-printed sample-holder for agitation-based decellularization purposes, designed for treating multiple specimens simultaneously and for improving efficiency, homogeneity and reproducibility of the decellularization treatment with respect to conventional agitation-based approaches. In detail, the proposed sample-holder is able to house up to four specimens and, immersed in the decellularizing solution within a beaker placed on a magnetic stirrer, to expose them to convective flow, enhancing the solution transport through the specimens while protecting them. Computational fluid dynamics analyses were performed to investigate the fluid phenomena establishing within the beaker and to support the sample-holder design. Exploratory biological tests performed on human skin specimens demonstrated that the sample-holder reduces process duration and increases treatment homogeneity and reproducibility

A C. elegans Model for Mitochondrial Fatty Acid Synthase II: The Longevity-Associated Gene W09H1.5/mecr-1 Encodes a 2-trans-Enoyl-Thioester Reductase

Our recognition of the mitochondria as being important sites of fatty acid biosynthesis is continuously unfolding, especially in light of new data becoming available on compromised fatty acid synthase type 2 (FASII) in mammals. For example, perturbed regulation of murine 17β-HSD8 encoding a component of the mitochondrial FASII enzyme 3-oxoacyl-thioester reductase is implicated in polycystic kidney disease. In addition, over-expression in mice of the Mecr gene coding for 2-trans-enoyl-thioester reductase, also of mitochondrial FASII, leads to impaired heart function. However, mouse knockouts for mitochondrial FASII have hitherto not been reported and, hence, there is a need to develop alternate metazoan models such as nematodes or fruit flies. Here, the identification of Caenorhabditis elegans W09H1.5/MECR-1 as a 2-trans-enoyl-thioester reductase of mitochondrial FASII is reported. To identify MECR-1, Saccharomyces cerevisiae etr1Δ mutant cells were employed that are devoid of mitochondrial 2-trans-enoyl-thioester reductase Etr1p. These yeast mutants fail to synthesize sufficient levels of lipoic acid or form cytochrome complexes, and cannot respire or grow on non-fermentable carbon sources. A mutant yeast strain ectopically expressing nematode mecr-1 was shown to contain reductase activity and resemble the self-complemented mutant strain for these phenotype characteristics. Since MECR-1 was not intentionally targeted for compartmentalization using a yeast mitochondrial leader sequence, this inferred that the protein represented a physiologically functional mitochondrial 2-trans-enoyl-thioester reductase. In accordance with published findings, RNAi-mediated knockdown of mecr-1 in C. elegans resulted in life span extension, presumably due to mitochondrial dysfunction. Moreover, old mecr-1(RNAi) worms had better internal organ appearance and were more mobile than control worms, indicating a reduced physiological age. This is the first report on RNAi work dedicated specifically to curtailing mitochondrial FASII in metazoans. The availability of affected survivors will help to position C. elegans as an excellent model for future pursuits in the emerging field of mitochondrial FASII research

Cardiac autonomic neuropathy in patients with diabetes and no symptoms of coronary artery disease: comparison of 123I-metaiodobenzylguanidine myocardial scintigraphy and heart rate variability

PURPOSE The purpose of this study was to evaluate the prevalence of cardiac autonomic neuropathy (CAN) in a cohort of patients with type 2 diabetes, truly asymptomatic for coronary artery disease (CAD), using heart rate variability (HRV) and (123)I-metaiodobenzylguanidine ((123)I-mIBG) myocardial scintigraphy. METHODS The study group comprised 88 patients with type 2 diabetes prospectively recruited from an outpatient diabetes clinic. In all patients myocardial perfusion scintigraphy, CAN by HRV and (123)I-mIBG myocardial scintigraphy were performed. Two or more abnormal tests were defined as CAN-positive (ECG-based CAN) and one or fewer as CAN-negative. CAN assessed by (123)I-mIBG scintigraphy was defined as abnormal if the heart-to-mediastinum ratio was 25%, or the total defect score was >13. RESULTS The prevalence of CAN in patients asymptomatic for CAD with type 2 diabetes and normal myocardial perfusion assessed by HRV and (123)I-mIBG scintigraphy was respectively, 27% and 58%. Furthermore, in almost half of patients with normal HRV, (123)I-mIBG scintigraphy showed CAN. CONCLUSION The current study revealed a high prevalence of CAN in patients with type 2 diabetes. Secondly, disagreement between HRV and (123)I-mIBG scintigraphy for the assessment of CAN was observed.Cardiovascular Aspects of Radiolog

Multiple Molecular Mechanisms Cause Reproductive Isolation between Three Yeast Species

Incompatibility between nuclear and mitochondrial genomes in yeast species may represent a general mechanism of reproductive isolation during yeast evolution

Investigating the GBA1-dependent regulation of GBA2 activity in Gaucher disease

Glycosphingolipids (GSLs) are a large and heterogeneous class of lipids, whose function is equally versatile and complex. They consist of a membrane anchor, ceramide, and different kinds of sugar head groups. Glucosylceramide (GlcCer) is the simplest GSL and serves as a building block for the synthesis of more complex GSLs. GlcCer is degraded either in the lysosome by the acid beta-glucosidase GBA1 or by the non-lysosomal beta-glucosidase GBA2, which is associated with membranes at the Golgi and ER. It is not known whether their distinct localisation points towards a different cellular function. Accumulation of GlcCer due to the lack of GBA2 results in male infertility, whereas various mutations in the GBA1 gene and loss of GBA1 activity cause the lipid-storage disorder Gaucher disease with different clinical subtypes. However, no genotype-phenotype correlation has been identified so far. The role of GBA2 in Gaucher disease pathology and its relationship to GBA1 is not well understood. My results reveal a GBA1-dependent down-regulation of GBA2 activity in patients suffering from Gaucher disease. I show that sphingosine, the cytotoxic metabolite accumulating in Gaucher cells through the action of GBA2, directly binds to GBA2 and inhibits its activity. I propose a negative feed-back loop that inhibits GBA2 activity in Gaucher cells through the action of sphingosine, preventing its further accumulation and cytotoxicity. My findings add a new chapter to the understanding of the complex molecular mechanism underlying Gaucher disease and the regulation of beta-glucosidase activity in general