Negative-pressure pulmonary edema presented with concomitant spontaneous pneumomediastinum: Moore meets Macklin

Negative-pressure pulmonary edema is an unusual complication mainly associated with general anesthesia. It is caused by excessive negative intrathoracic pressure following a deep inspiration against an acute airway obstruction. The resultant decreased intrathoracic pressure amplifies venous return to the right heart and increases pulmonary capillary wedge pressure that can be further amplified by massive sympathetic discharge due to hypoxia. The combination of increased venous return and pulmonary capillary wedge pressure favours the shift of fluid into the pulmonary interstitium with resultant pulmonary edema. Conversely, spontaneous pneumomediastinum (SP) results from alveolar rupture following an excessive positive intrathoracic pressure. The air leaks out of the alveoli and along the perivascular space toward the mediastinum. We experienced a case of negative pulmonary edema which presented in association with SP. Pneumomediastinum is probably caused by an excessive positive intrathoracic pressure for a subsequent expiration against a closed airway. In the present case, both complications resolved with conservative management

PANEV: an R package for a pathway-based network visualization

BACKGROUND: During the last decade, with the aim to solve the challenge of post-genomic and transcriptomic data mining, a plethora of tools have been developed to create, edit and analyze metabolic pathways. In particular, when a complex phenomenon is considered, the creation of a network of multiple interconnected pathways of interest could be useful to investigate the underlying biology and ultimately identify functional candidate genes affecting the trait under investigation. RESULTS: PANEV (PAthway NEtwork Visualizer) is an R package set for gene/pathway-based network visualization. Based on information available on KEGG, it visualizes genes within a network of multiple levels (from 1 to n) of interconnected upstream and downstream pathways. The network graph visualization helps to interpret functional profiles of a cluster of genes. CONCLUSIONS: The suite has no species constraints and it is ready to analyze genomic or transcriptomic outcomes. Users need to supply the list of candidate genes, specify the target pathway(s) and the number of interconnected downstream and upstream pathways (levels) required for the investigation. The package is available at https://github.com/vpalombo/PANEV

Machine Learning approaches for the design of biomechanically compatible bone tissue engineering scaffolds

Triply-Periodic Minimal Surfaces (TPMS) analytical formulation does not provide a direct correlation between the input parameters (analytical) and the mechanical and morphological properties of the structure. In this work, we created a dataset with more than one thousand TPMS scaffolds for the training of Machine Learning (ML) models able to find such correlation. Finite Element Modeling and image analysis have been used to characterize the scaffolds. In particular, we trained three different ML models, exploring both a linear and non-linear approach, to select the features able to predict the input parameters. Furthermore, the features used for the prediction can be selected in three different modes: i) fully automatic, through a greedy algorithm, ii) arbitrarily, by the user and iii) in a combination of the two above methods: i.e. partially automatic and partially through a user-selection. The latter, coupled with the non-linear ML model, exhibits a median error less than 3% and a determination coefficient higher than 0.89 for each of the selected features, and all of them are accessible during the design phase. This approach has been applied to the design of a hydroxyapatite TPMS scaffolds with prescribed properties obtained from a real trabecular-like hydroxyapatite scaffold. The obtained results demonstrate that the ML model can effectively design a TPMS scaffold with prescribed features on the basis of biomechanical, mechanobiology and technological constraints

RGD-containing Peptides Inhibit Fibrinogen Binding to Platelet αIIbβ3 by Inducing an Allosteric Change in the Amino-terminal Portion of αIIb

To determine the molecular basis for the insensitivity of rat alpha(IIb)beta(3) to inhibition by RGD-containing peptides, hybrids of human and rat alpha(IIb)beta(3) and chimeras of alpha(IIb)beta(3) in which alpha(IIb) was composed of portions of human and rat alpha(IIb) were expressed in Chinese hamster ovary cells and B lymphocytes, and the ability of the tetrapeptide RGDS to inhibit fibrinogen binding to the various forms of alpha(IIb)beta(3) was measured. These measurements indicated that sequences regulating the sensitivity of alpha(IIb)beta(3) to RGDS are located in the seven amino-terminal repeats of alpha(IIb). Moreover, replacing the first three or four (but not the first two) repeats of rat alpha(IIb) with the corresponding human sequences enhanced sensitivity to RGDS, whereas replacing the first two or three repeats of human alpha(IIb) with the corresponding rat sequences had little or no effect. Nevertheless, RGDS bound to Chinese hamster ovary cells expressing alpha(IIb)beta(3) regardless whether the alpha(IIb) in the heterodimers was human, rat, or a rat-human chimera. These results indicate that the sequences determining the sensitivity of alpha(IIb)beta(3) to RGD-containing peptides are located in the third and fourth amino-terminal repeats of alpha(IIb). Because RGDS binds to both human and rat alpha(IIb)beta(3), the results suggest that differences in RGDS sensitivity result from differences in the allosteric changes induced in these repeats following RGDS binding

Assignment of the binding site for Haptoglobin on Apolipoprotein A-I

Haptoglobin (Hpt) was previously found binding the high-density lipoprotein (HDL) Apolipoprotein A-I (ApoA-I) and able to inhibit the ApoA-I-dependent activity of the enzyme Lecithin:Cholesterol Acyl-Transferase (LCAT), which plays a major role in the reverse cholesterol transport. The ApoA-I structure was analyzed for detecting the site bound by Hpt. ApoA-I was treated by cyanogen bromide or hydroxylamine and the resulting fragments, separated by electrophoresis or gel filtration, were tested by Western blotting or ELISA for their ability to bind Hpt. The ApoA-I sequence from Glu113 to Asn184 harbored the binding site for Hpt. Biotinylated peptides were synthesized overlapping such a sequence, and their Hpt binding activity was determined by avidin-linked peroxidase. The highest activity was exhibited by the peptide P2a, containing the ApoA-I sequence from Leu141 to Ala164. Such a sequence contains an ApoA-I domain required for binding cells, promoting cholesterol efflux, and stimulating LCAT. The peptide P2a effectively prevented both binding of Hpt to HDL-coated plastic wells and Hpt-dependent inhibition of LCAT, measured by anti-Hpt antibodies and cholesterol esterification activity respectively. The enzyme activity was not influenced, in the absence of Hpt, by P2a. Differently from ApoA-I or HDL, the peptide did not compete with Hemoglobin for Hpt binding in ELISA experiments. The results suggest that Hpt might mask the ApoA-I domain required for LCAT stimulation, thus impairing the HDL function. Synthetic peptides, able to displace Hpt from ApoA-I without altering its property of binding Hemoglobin, might be used for treatment of diseases associated with defective LCAT function

Lymphectomy in the treatment of thyroid cancer in adults and children.

Thyroid carcinoma is thè most frequent endocrine malignancy in Italy and differs in naturai history according to histological type and age of patients. Lymph node metastases are more frequently seen in young patients with papillary carcinoma. However, many clinical series suggested that although thè incidence of lymph node invasion in high-risk patients (over-50s) is slightiy lower than in low-risk patients, thè locai recurrence rate is higher than in thè former. From thè results of our experience, confirmed by other authors, we retain total thyroidectomy with lymphectomy of thè centrai compartment as thè procedure of choice in thè treatment of well-differentiated thyroid carcinoma in thè under-50s. In thè over-50s, functional bilateral lymphectomy improves survival and should be considered mandatory, just as for medullary carcinoma. On thè contrary, thè prognosis of anaplastic carcinoma is not improved by lymphectomy

Effect of antithrombotic therapy on postoperative outcome of 538 consecutive emergency laparoscopic cholecystectomies for acute cholecystitis. Two Italian center’s study

The risk of developing hemorrhagic complications during or after emergency cholecystectomy (EC) for acute cholecystitis (AC) in patients with antithrombotic therapy (ATT) remains uncertain. In this double-center study, we evaluated post-operative outcomes in patients with ATT undergoing EC. We retrospectively evaluated 538 patients who underwent laparoscopic EC for AC between May 2015 and December 2019 at two referral centers. 89 of them (17%) were on ATT. We defined postoperative complication rates, including bleeding, as our primary outcome. Mortality was higher in the ATT group. Morbidity was higher in the ATT group as well; however, the difference was not statistically significant. 12 patients (2%) experienced intraoperative blood loss over 500 ml and ten (2%) had postoperative bleeding complications. Two patients (< 1%) experienced both intraoperative and postoperative bleeding. On multivariate analysis, ATT was not significantly associated with worse postoperative outcomes. Antithrombotic therapy is not an independently associated factor of severe postoperative complications (including bleeding) or mortality. However, these patients still represent a challenging group and must be carefully managed to avoid postoperative bleeding complications