Excerpta de uniformitate et difformitate: A Physical-Matemathical Compilation in Ms. Paris, Bl. De l’Arsenal, Lat. 522 Unknown Until Today

El objetivo principal de este trabajo es presentar nuevos materiales relacionados con el desarrollo de la llamada tradición de los calculatores de fines del siglo XIV en París. Es sabido que esta tradición surgió en el Merton College en Oxford alrededor de 70 años atrás y propuso un nuevo enfoque para la filosofía natural o “física” que consiste en el uso generalizado de métodos matemáticos o “medio-matemáticos” para analizar y discutir cuestiones que involucrasen movimiento y cualidades. El manuscrito Lat. 522 de la biblioteca de Arsenal fue copiado íntegramente por u hombre llamado “Johannes Monachus”, que puede posiblemente ser asociado con el famoso filósofo y teólogo Pierre D’Ailly. Aparte de otros trabajos significativos, Johannes Monachus copió los tratados De configurationes (de Nicole Oresme) y De latitudinibus formarum (de Jacobus de Sancto Martino). Hacia el final de este último trabajo decidió completar la “latitud de formas” con “algunas otras cosas” (cum quibusdam aliis), un texto corto que muy probablemente él mismo compiló usando las Regulae de Heytesbury y otras fuentes similares y por lo que el título Excerpta de uniformitate et difformitate puede haber sido dado. El siguiente trabajo presenta una transcripción de este texto corto, expone su contenido y discute su significado en el contexto de la tradición de los calculadores. En adición, se brinda una descripción completa del manuscrito.The main purpose of this paper is to present some new materials related to the development of the so called calculatores – tradition at the end of the 14th century in Paris. It is well known that this tradition emerged at the Merton College in Oxford about 70 years before and proposed a new approach to natural philosophy or “physics” consisting in the generalized use of mathematical and “half-mathematical” methods of analyzing and discussing questions concerned with motions and qualities. The manuscript Lat. 522 of the Arsenal Library was entirely copied by a man called “Johannes Monachus”, who can possibly be associated with the famous philosopher and theologian Pierre D’Ailly. Besides other significant works, Johannes Monachus copied the tracts De configurationibus (by Nicole Oresme) and De latitudinibus formarum (by Jacobus de Sancto Martino). At the end of this last work he decided to complete the “latitude of forms” with “some further things” (cum quibusdam aliis), a short text which most probably he himself compiled using the Regulae by Heytesbury and other similar sources and to which the title Excerpta de uniformitate et difformitate may be given. The following paper gives a transcription of this short text, expounds its content and discusses its significance in the context of the tradition of the late calculators. In adittion, a full description of the manuscript is given

Strangulated hiatal hernia remains a challenge in surgical emergency: Literature review and our experience

Introduction. Upside-down stomach (UDS) is the rarest type of hiatal hernia (<5%). It is characterized by herniation of the entire stomach or most gastric portions into the posterior mediastinum. It is a very rare condition and it is associated with a risk of incarceration as well as volvulus development. All of these complications represent true emergencies as life-threatening conditions. Material & methods. Case 1: A 62-year-old woman with an incarcerated and ischemic paraesophageal hiatal hernia with a stomach perforation. A total gastrectomy was performed with a Roux en-Y esophago-jejunostomy. The patient was discharged after 15 days without any complication. Case 2: A 84-year-old woman with the evidence at the computer tomography scan all of her stomach and parts of her jejunum and pancreas were drawn into the hernia sac herniated in her thorax. An exploratory laparotomy was performed which showed edematous intraperitoneal portion of the pyloric antrum, a total gastrectomy was performed and Roux en-Y esophago-jejunostomy was performed. The patient was placed in the intensive care unit, where she was instable and she developed sepsis. She died on 7th postoperative day. Case 3: A 76-year-old man presented in our department as emergency with the diagnosis of an incarcerated and ischemic paraesophageal hiatal hernia. An exploratory laparotomy was performed which showed an incarcerated and strangulated hiatal hernia. A section of the cardias and the body of the stomach was performed. The patient was placed in the intensive care unit, where he was instable and he developed sepsis which caused his death. Discussion. Surgery for incarcerated paraesophageal hernia or upside-down stomach has to be performed emergently as incarceration can become irreversible and severe bleeding can occur due to distension and vascular dilation. Moreover, ischemia and gastric perforation are on the verge. However, there are no clear evidence or existing guidelines on the management of acute paraesophageal hernia or upside-down stomach. In our literature review we analyzed clinical case reports and case series studies of strangulated hiatal hernia published between 2013 and 2019 published in PubMed. Conclusion. Management of strangulated hiatal hernia remains a challenge in general surgery. Open approach is suggested for unstable patients and an emergent laparoscopic reduction and repair is reasonable in stable patients

Management of bile duct injuries after cholecystectomy: Therapeutic approach and examination of possible sources of error. Report of 2 cases

Background: Bile duct injuries is the primary concern of general surgeons during and after cholecystectomy, with an incidence ranging from 0.08% to 0.4%. Through the description of two cases we intend to discuss the management of most frequent types of bile duct injuries after cholecystectomy and examine some possible sources of error. Case reports: We have treated 2 cases previously operated by other surgical teams. Case report 1: patient undergoing laparoscopic cholecystectomy with lesion of the main bile duct, treated with its reconstruction with positioning of a T-drainage tube. Case report 2: patient with jaundice previously treated for incarcerated incisional hernia and gallbladder stones. We verified the presence of a stenosis of the main bile duct which was resolved with the positioning of a T-tube drainage Discussion: Many descriptions and classifications regarding iatrogenic lesions of the bile duct after cholecystectomy have been described, although some of them represent a good guide on the surgical approach to be adopted, but the surgical skills possessed by the operator remain the most important variables Conclusions: All possible precautions must be considered in order to avoid the possibility of damaging the biliary tree. In our opinion an anterograde approach during cholecystectomy offers greater safety

Right hemicolectomy: Laparoscopic versus robotic approach

BACKGROUND: Minimally invasive surgery for colorectal cancer has been demonstrated to have the same oncological results as open surgery, with better clinical outcomes. Robotic surgery is an evolution of minimally invasive technique. This study aims to evaluate surgical and oncological short-term outcomes of robotic right colon resection in comparison with the laparoscopic approach. METHODS: Between January 2014 and May 2017, fifteen laparoscopic right hemicolectomies were compared to seven robotic ones. The primary data points included operation time, length of hospital stay, extraction site incision length, complications, and conversions. When malignancy was the indication for surgery, additional data points have been added. RESULTS: The study showed no difference in parameters between the two groups, but estimated blood loss was significantly smaller for Robotic arm. We found a prolonged total operative room time in the robotic arm, while the surgical time is similar in two groups. The data collected about specimen length and number of lymph nodes suggest that robotic procedure is oncologically similar to laparoscopic one. CONCLUSIONS: Robotic approach allows performance of adequate dissection of the right colon with radical lymphadenectomy as in laparoscopic surgery, confirming the safety and oncological efficacy of this technique, with acceptable results and short-term outcomes

Bilateral central neck dissection in the treatment of early unifocal papillary thyroid carcinomas with poor risk factors: A mono-institutional experience

INTRODUCTION: Papillary thyroid carcinoma is the most common type of thyroid cancer worldwide. While total thyroidectomy is widely considered the standard surgical approach for papillary thyroid carcinomas, the role of central lymphadenectomy in early stage poor-risk papillary thyroid tumors is still a matter of debate. This study was designed to assess surgical complications and local disease control rates in patients affected by poor-risk early stage papillary thyroid carcinomas. METHODS: We retrospectively analyze three groups of patients affected by poor-risk early stage papillary thyroid carcinomas treated with three alternative surgical strategies: i) routine total thyroidectomy; ii) total thyroidectomy and routine central lymphadenectomy; iii) total thyroidectomy and central lymphadenectomy upon positive intraoperative histological evaluation of lymph node involvement. RESULTS: Data from patients treated with routine total thyroidectomy showed 32% of persistence of disease in the central compartment with concurrent positivity in laterocervical compartment in 25% of these cases. By contrast, patients receiving total thyroidectomy and routine central lymphadenectomy showed the involvement of central compartment in 40% of cases, while the remaining 60% of patients were free from lymph node metastases. Finally, patients undergoing total thyroidectomy and central lymphadenectomy upon positive intraoperative lymph node biopsy exhibited lack of persistence of lymph node involvement in central compartment after surgery. Of note, postsurgical complications were lower in patients undergoing conservative surgical approaches. CONCLUSIONS: These data suggest that central lymphadenectomy, performed only in case of positive intraoperative lymph node biopsy, ensures reduced incidence of postoperative complications and optimal loco-regional disease control

Organic cation transporters (OCTs/OCTNs) in human primary alveolar epithelial cells

Alveolar epithelium, besides exerting a key role in gas exchange and surfactant production, plays important functions in host defense and inflammation. Pathological conditions associated to alveolar dysfunction include Acute Respiratory Distress Syndrome (ARDS), asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). The use of predictive in vitro models of human alveolar epithelium is nowadays required for the study of disease mechanisms, as well as of pharmacokinetic parameters of pulmonary drugs delivery. Here, we employed a novel 3D model of human alveoli, namely EpiAlveolar™, consisting of primary alveolar epithelial cells, pulmonary endothelial cells and fibroblasts, that reflects properly the in vivo-like conditions. In EpiAlveolar™ we performed a characterization of Organic Cation Transporters (OCTs and OCTNs) expression and activity and we found that OCTN2, OCT1 and OCT3 are expressed on the basolateral membrane; instead, ATB0,+ transporter for cationic and neutral amino acids, which shares with OCTN2 the affinity for carnitine as substrate, is readily detectable and functional at the apical side. We also show that these transporters differentially interact with anticholinergic drugs. Overall, our findings reveal close similarities of EpiAlveolar™ with the tracheal/bronchial epithelium (EpiAirway™ model) and entrust this alveolar tissue as a potential tool for the screening of biopharmaceuticals molecules

Organic cation transporters (OCTs) in EpiAirway™, a cellular model of normal human bronchial epithelium

Organic cation transporters (OCTs) and novel organic cation transporters (OCTNs) are responsible for drug delivery in the intestine and kidney; in the lung, OCTs mediate inhaled drugs' transport, although their physiological role in airways remains poorly understood. The studies addressing OCTs/OCTNs in human airways were mostly performed in immortal or transformed cell lines; here, we studied OCTs in EpiAirway, a recently developed in vitro model of normal bronchial epithelium. Calu-3 monolayers were used for comparison. The activity of OCTs was evaluated by measuring the uptake of 1-methyl-4-phenylpyridinium (MPP+) at the apical and basolateral side of monolayers and protein expression through Western Blot analysis. OCTs and OCTNs expression, along with that of Amino acid Transporter B0,+ (ATB0,+)transporter, was determined by measuring the number of mRNA molecules through quantitative Polymerase Chain Reaction (qPCR). The interaction of the transporters with bronchodilators was also assessed. Results highlight significant differences between Calu-3 cells and EpiAirway, since, in the latter, OCTs are active only on the basolateral membrane where they interact with the bronchodilator ipratropium. No activity of OCTs is detectable at the apical side; there, the most abundant carrier is, instead, SLC6A14/ATB0,+, that can thus be potentially listed among organic cation transporters responsible for drug delivery in the lung

Human macrophage differentiation induces OCTN2-mediated L-carnitine transport through stimulation of mTOR-STAT3 axis

l-Carnitine, in addition to playing a fundamental role in the β-oxidation of fatty acids, has been recently identified as a modulator of immune function, although the mechanisms that underlie this role remain to be clarified. In this study, we addressed the modulation of l-carnitine transport and expression of related transporters during differentiation of human monocytes to macrophages. Whereas monocytes display a modest uptake of l-carnitine, GM-CSF-induced differentiation massively increased the saturable Na+-dependent uptake of l-carnitine. Kinetic and inhibition analyses demonstrate that in macrophage l-carnitine transport is mediated by a high-affinity component (Km ∼4 µM) that is identifiable with the operation of OCTN2 transporter and a low-affinity component (Km > 10 mM) that is identifiable with system A for neutral amino acids. Consistently, both SLC22A5/OCTN2 and SLC38A2/SNAT2 are induced during the differentiation of monocytes to macrophages at gene and protein levels. Elucidation of GM-CSF signaling demonstrates that the cytokine causes the activation of mTOR kinase, leading to the phosphorylation and activation of STAT3, which, in turn, is responsible for OCTN2 transcription. SLC22A5/OCTN2 therefore emerges as a novel member of the set of genes markers of macrophage differentiation

Erratum: Functional analysis of OCTN2 and ATB0,+ in normal human airway epithelial cells (PLoS ONE (2020) 15:2 (e0228568) DOI: 10.1371/journal.pone.0228568)

There is an error in reference 12. The correct reference is: Ingoglia F, Visigalli R, Rotoli BM, Barilli A, Riccardi B, Puccini P, et al. (2016) Functional activity of L-carnitine transporters in human airway epithelial cells. Biochim Biophys Acta. 1858(2):210–9. 10.1016/j.bbamem.2015. 11.013