Humerus Fracture in a Buff-necked Ibis (Theristicus caudatus) - Anesthesia and Surgical Procedures

Background: The medical science of birds, with the exception of aviculture, has a very short history compared to other subdisciplines of veterinary medicine. With this in mind, the current work aims to report the case of a buff-necked ibis with an open fracture of the left humerus, presenting the surgical treatment and anesthetic protocol used, in order to contribute to the avian medical literature.Case: An adult buff-necked ibis (Theristicus caudatus) was referred to the University Veterinary Hospital with an open fracture of the left humeral shaft, 7 days after rescue. During the physical examination, a skin lesion was identified in the fracture area, with signs of low vascularization, devitalization, necrotic tissues, and purulent secretions being noted. On radiographic examination, the fracture was classified as comminuted, with exposure of the left humeral shaft. After evaluatingthe limb, it was decided to amputate the wing, and 24 h later, the patient was referred to the operating room after fasting for 4 h. As pre-anesthetic medication, ketamine (20 mg/kg) and midazolam (1 mg/kg) were administered, both intramuscularly. Orotracheal intubation was performed, after which the tracheal tube was connected to a Baraka-type gas-free system andthe supply of isoflurane was started through a universal vaporizer, diluted in 100% oxygen. For transoperative analgesia, brachial plexus block was performed using 2% lidocaine (2 mg/kg). During the surgical procedure, an incision was made in the skin and subcutaneous tissue in the middle third of the left humerus, and detachment of the greater deltoid muscle was performed with a periosteal elevator, followed by excision of the tensor propatagialis. In the ventrodorsal region, circular ligation of the brachial vein, ulnar vein and artery, and median-ulnar nerve was carried out, and disarticulation of the scapulacoracoid-humeral region. Subsequently, abolition of dead space and a myorrhaphy were performed, followed by demorrhaphy. In the immediate post-operative period, morphine (5 mg/kg), meloxicam (0.1 mg/kg), and enrofloxacin (10 mg/kg) were administered intramuscularly. The patient was discharged from the hospital 6 h after the end of the surgical procedure.Discussion: Interest in the conservation of wild birds is one of the causes of the increased demand for anesthetic and surgical procedures in these species. However, it is a challenge for professionals in the field. The use of analgesics is recommended for reasons of well-being, but also because of the possibility of reducing the concentration of inhalational anesthetics in surgical procedures. Ketamine associated with midazolam promotes sufficient sedation and muscle relaxation in the patient, enabling safe preoperative management, in addition to reducing the amount of inhaled anesthetics used during the transoperative period. Isofluorane promotes safe general anesthesia for birds and has an advantage over injectable drugs, as it provides better dynamic control of anesthetic depth in these species. The brachial plexus block performed is a simple procedure that promotes quality anesthesia and analgesia in the perioperative period. The choice for amputation was due to the absence of musculature for closure, severe skin, muscle, and bone devitalization, and the infectious process in the region, factors that would prevent osteosynthesis. Although amputation through the bone is preferable, the disarticulation technique was used due to the absence of a healthy proximal humeral fragment. The patient’s death can be explained by the poor nutritional status the bird was in, as it presented an open fracture with severe contamination, a concomitant injury that occurred during the possible trauma, and the excessive time between the day of the trauma and the day of medical attendance. However, the surgical and anesthetic procedures were adequate and satisfactory for the patient. The importance of identifying and treating diseases secondary to contaminated fractures in these species is emphasized. Keywords: bird, avian medicine, fauna, lesions, recovery. Título: Fratura de úmero em uma curicaca (Theristicus caudatus) - manejo anestésico e cirúrgico Descritores: aves, medicina aviária, fauna, lesões, recuperação

Molecular mechanism of action of trimethylangelicin derivatives as CFTR modulators

The psoralen-related compound, 4,6,40-trimethylangelicin (TMA) potentiates the cAMP/PKA-dependent activation of WT-CFTR and rescues F508del-CFTR-dependent chloride secretion in both primary and secondary airway cells homozygous for the F508del mutation. We recently demonstrated that TMA, like lumacaftor (VX-809), stabilizes the first membrane-spanning domain (MSD1) and enhances the interface between NBD1 and ICL4 (MSD2). TMA also demonstrated anti-inflammatory properties, via reduction of IL-8 expression, thus making TMA a promising agent for treatment of cystic fibrosis. Unfortunately, TMA was also found to display potential phototoxicity and mutagenicity, despite the fact that photo-reactivity is absent when the compound is not directly irradiated with UVA light. Due to concerns about these toxic effects, new TMA analogs, characterized by identical or better activity profiles and minimized or reduced side effects, were synthesized by modifying specific structural features on the TMA scaffold, thus generating compounds with no mutagenicity and phototoxicity. Among these compounds, we found TMA analogs which maintained the potentiation activity of CFTR in FRT-YFP-G551D cells. Nanomolar concentrations of these analogs significantly rescued F508del CFTR-dependent chloride efflux in FRT-YFP-F508del, HEK-293 and CF bronchial epithelial cells. We then investigated the ability of TMA analogs to enhance the stable expression of varying CFTR truncation mutants in HEK-293 cells, with the aim of studying the mechanism of their corrector activity. Not surprisingly, MSD1 was the smallest domain stabilized by TMA analogs, as previously observed for TMA. Moreover, we found that TMA analogs were not effective on F508del-CFTR protein which was already stabilized by a second-site mutation at the NBD1-ICL4 interface. Altogether, our findings demonstrate that these TMA analogs mediate correction by modifying MSD1 and indirectly stabilizing the interface between NBD1 and CL4

Postoperative Analgesia with Transdermal Fentanyl or Intramuscular Methadone in Dogs Submitted to Thoracolumbar Hemilaminectomy

Background: Postoperative care after thoracolumbar hemilaminectomy in dogs generally includes rest, physical therapy, and analgesics such as opioids. Currently, there is no established standard for the management of postoperative pain in patients undergoing hemilaminectomy. Ideally, an analgesic protocol should provide adequate pain relief with limited sedation, low adverse effects, and postoperative patient comfort. Therefore, this study aimed to evaluate postoperative analgesia using transdermal fentanyl or intramuscular methadone in dogs undergoing thoracolumbar hemilaminectomy associated with intervertebral disc fenestration (HT) for the treatment of intervertebral disc extrusion (IVDE).Materials, Methods & Results: Eight dogs from the Department of Neurology and Neurosurgery of a veterinary teaching hospital, submitted to HT for the treatment of IVDE, were included. The dogs were randomly distributed into two groups of equal numbers, namely the transdermal fentanyl (FT) group and the intramuscular methadone (IM) group. At the end of the surgical procedure, a fentanyl adhesive patch was applied to the animals in the FT group, which remained there for 72 h. In the IM group, analgesia was induced by intramuscular administration of methadone at intervals of 6 h until 72 h after surgery. The animals were evaluated using the short form of the Glasgow Composite Pain Scale (SF-GCPS). Evaluations of physiological parameters, side effects, and pain were performed by two assessors who had experience using the pain scale and were blinded to the analgesic protocol. Pain evaluations were performed every 2 h (from T4) until 24 h after the surgical procedure. Evaluations were performed every 4 h from 24 h to 48 h after the surgical procedure and at intervals of 24 h from 48 h to 72 h.Discussion: Transdermal fentanyl provided the lowest pain scores, when evaluated by the SF-GCPS, for both assessors. These data are presented as a function of time in Figure 1, which shows the variation in pain scores by SF-GCPS over time. It should be noted that, for both assessors, animals in the FT group had lower pain scores than animals in the IM group. There was also less variation in pain scores in the FT group, indicating better analgesic quality. This can be explained by the maintenance of the drug’s plasma concentrations in a stable manner, avoiding periods of greater or lesser pain throughout the evaluation period due to the absence of increases or decreases in plasma concentration. In the IM group, three analgesic rescues were required; in the FT group, there was no rescue. Although the data indicate that IM was responsible for a greater occurrence in the number of rescues, it is worth noting that this information is based on a small group of animals. One dog needed two rescues (at T4 and T8), regarding which both assessors agreed, while another required one rescue (at T18), but there was a difference of one point between the raters. However, pain scores in all of the cases were considered to be mild, not moderate or severe, with rescues occurring on scores of 5/20. Both fentanyl used by the transdermal route and intramuscular methadone promoted analgesia in the first three postoperative days in dogs undergoing HT. Better stability in postoperative pain scores without the need for analgesic rescue and less occurrence of adverse effects were observed in dogs treated with FT.Keywords: fentanyl patch, neurosurgery, dogs, analgesia, pain.Título: Analgesia pós-operatória com Fentanil transdérmico ou Metadona intramuscular em cães submetidos à hemilaminectomia toracolombar Descritores: adesivo fentanil, neurocirurgia, cães, analgesia, dor

CO2 electroreduction catalyzed by Cu nanocrystal

reservedIl cambiamento climatico, innescato dalle emissioni di CO2 dovute ad attività umane in costante crescita a partire della prima rivoluzione industriale (1760-1840), rappresenta una delle sfide più pressanti del nostro tempo. La dipendenza mondiale dai combustibili fossili spinge sempre più la ricerca scientifica ad individuare possibili soluzioni con un minor impatto ambientale con studi per catturare, immagazzinare e convertire in prodotti utili la CO2 atmosferica. La conversione della CO2 in molecole di maggior pregio può avvenire con un approccio elettrochimico di elettroriduzione catalizzata in fase eterogenea. Il rame metallico è un materiale che presenta ottime proprietà catalitiche nei confronti della reazione di elettroriduzione della CO2 (ECO2RR); diretta conseguenza è che i catalizzatori più popolari nella ECO2RR sono nanocristalli di Cu con morfologie controllate i quali permettono di sviluppare processi con attività e selettività elevate, grazie ad interazioni preferenziali tra la CO2 ed i suoi intermedi di reazione e determinate superfici cristallografiche. I prodotti principali che è possibile ottenere costituiscono combustibili e importanti precursori chimici dell’industria chimica di base: troviamo molecole ad un atomo di carbonio (C1), quali CH3OH e HCOO– e a due o più atomi di carbonio (C2): CH2CH2, CH3CH2OH, CH3COCH3 e CH3COO–. Oggetto di questa tesi è la sintesi di nanocristalli quali nanocubi (CuNCs) e nanofili (CuNWs) in Cu, la loro caratterizzazione e l’indagine del loro comportamento catalitico nella CO2RR con il fine ultimo di individuare i parametri che regolano la selettività ed eventualmente la resa nei confronti dei prodotti. La resa di produzione in riferimento a un prodotto è valutata come efficienza faradica. Saranno indagate variabili quali il potenziale di riduzione, l’influenza di differenti elettroliti e supporti, oltre che l’influenza di trattamenti superficiali eseguiti sul catalizzatore con operazioni di etching chimico o impiego di molecole organiche come alcantioli

Sintesi di analoghi di TMA per la modulazione di CFTR

Sintesi di nuovi analoghi di TMA per la modulazione di CFTR e il trattamento della fibrosi cistic

The crisis communication in luxury brands. The Balenciaga case

reservedLo scopo di questa tesi è delineare il processo e le modalità di gestione dei fenomeni di comunicazione di crisi che le organizzazioni, le imprese e le aziende si possono trovare ad affrontare nel corso del loro ciclo di vita. Il focus della ricerca è incentrato sullo studio delle dinamiche di crisis management che avvengono nel settore dei brand di moda di lusso. Verrà trattato nello specifico il caso dell’azienda di moda e luxury brand Balenciaga avvenuto tra novembre e dicembre 2022 a seguito di una serie di errori comunicativi e pubblicitari che hanno generato scandali mediatici e una crisi per la reputazione dell’azienda. Il primo capitolo della tesi mira a descrivere il concetto di comunicazione di crisi spiegandone le tipologie fondamentali, le fasi in cui si sviluppa e si gestisce una crisi, le teorie prodotte dalla letteratura a riguardo e l’impatto che i social media e il web hanno su questi eventi. Nel secondo capitolo viene data una panoramica generale della comunicazione nel settore della moda di lusso, studiando il processo di digitalizzazione del lusso, e si proporranno alcuni esempi di casi storici ed emblematici di comunicazione di crisi dei luxury brand. Il terzo capitolo tratta del caso oggetto della tesi, ripercorrendo brevemente la storia dell’azienda di moda e brand di lusso Balenciaga, analizzandone in particolare la brand identity e le principali tecniche comunicative utilizzate, per poi descrivere gli eventi che hanno condotto alla crisi e allo scandalo mediatico. Il capitolo si conclude con la spiegazione di come il team di Balenciaga ha comunicato e gestito questo evento critico. Nel quarto capitolo conclusivo viene inizialmente proposta un’analisi della gestione della comunicazione di crisi di Balenciaga attraverso le teorie e i modelli introdotti nel primo capitolo, per poi fornire una personale interpretazione di quelli che sono stati gli errori e le mancanze commessi, e concludendo con una proposta di quello che si sarebbe dovuto o potuto fare per attuare una comunicazione di crisi più adeguata ed efficace. Gli strumenti principali utilizzati per ricavare le informazioni sono stati i testi Luxory Brand Management. Una visione completa sull’identità e la gestione del settore del lusso (Chevalier M., Mazzalovo G., 2008, FrancoAngeli), Leading companies through storms and crisis. Principles and best practices in conflict prevention, crisis management and communication (De La Cierva Y., 2018, Pearson), Crisis Management. Come affrontare e gestire emergenze e imprevisti (Lagadec P., 2002, FrancoAngeli), Il neo-lusso. Marketing e consumi di qualità in tempi di crisi (Mattia G., 2013, FrancoAngeli), Crisis Management e Crisis Communication. La rilevanza della comunicazione nella gestione delle crisi d’impresa (Piciocchi P., 2018, G. Giappichelli Editore), La comunicazione di crisi e i social media. Principi, modelli teorici e applicazioni pratiche (Splendiani S. 2002, FrancoAngeli)

Short-term outcome of adenosine–lidocaine–magnesium polarizing cardioplegia in humans

OBJECTIVES: Hyperkalaemic depolarized myocardial arrest is the cornerstone of myocardial protection, although some potassiumrelated cytotoxicity has been demonstrated. Polarized arrest has gained interest because of a reported better myocardial protection in preclinical studies. The goal of this study was to analyse the quality of myocardial protection and hospital outcome after normokalaemic adenosine–lidocaine–magnesium (ALM) blood polarizing cardioplegia, compared to hyperkalaemic blood Buckberg depolarizing cardioplegia, in elective routine adult cardiac surgery. METHODS: One thousand consecutive elective adult cardiac patients [627 undergoing ALM-polarizing cardioplegia (ALM-POL) vs 373 Buckberg depolarized cardioplegia (BUCK-DEPOL)] who were operated on were analysed. Perioperative leakage of high-sensitivity troponin I (Hs-TnI), peripheral lactate, inotropic and vasoactive daily requirement [maximal vasoactive inotropic score (VISMAX)], hospital mortality and morbidity were collected and compared in the overall population and in the propensity score (PS) matched population (206 pairs). RESULTS: A significantly lower leakage of Hs-TnI during hospitalization was detected in patients receiving ALM-POL versus those receiving BUCK-DEPOL (group time P < 0.001 for overall population and PS matched pairs). The maximum value of postoperative Hs-TnI was also lower after ALM-POL (P < 0.001 in both cohorts), and spontaneous recovery of sinus rhythm at aortic declamping was higher (P < 0.001 in favour of ALM-POL). Maximal VISMAX during hospitalization was significantly higher after BUCK-DEPOL in both cohorts (P = 0.019 for overall population; P = 0.031 for PS matched population), with significantly higher VISMAX on the day of surgery in BUCK-DEPOL PS matched patients (P = 0.042). No other significant differences in hospital morbidity and mortality were found. CONCLUSIONS: Despite comparable short-term clinical outcomes, ALM-POL cardioplegia proved superior in terms of quality of myocardial protection compared to BUCK-DEPOL cardioplegia in elective routine adult cardiac surgery

Humerus Fracture in a Buff-necked Ibis (Theristicus caudatus) - Anesthesia and Surgical Procedures

Background: The medical science of birds, with the exception of aviculture, has a very short history compared to other subdisciplines of veterinary medicine. With this in mind, the current work aims to report the case of a buff-necked ibis with an open fracture of the left humerus, presenting the surgical treatment and anesthetic protocol used, in order to contribute to the avian medical literature.Case: An adult buff-necked ibis (Theristicus caudatus) was referred to the University Veterinary Hospital with an open fracture of the left humeral shaft, 7 days after rescue. During the physical examination, a skin lesion was identified in the fracture area, with signs of low vascularization, devitalization, necrotic tissues, and purulent secretions being noted. On radiographic examination, the fracture was classified as comminuted, with exposure of the left humeral shaft. After evaluatingthe limb, it was decided to amputate the wing, and 24 h later, the patient was referred to the operating room after fasting for 4 h. As pre-anesthetic medication, ketamine (20 mg/kg) and midazolam (1 mg/kg) were administered, both intramuscularly. Orotracheal intubation was performed, after which the tracheal tube was connected to a Baraka-type gas-free system andthe supply of isoflurane was started through a universal vaporizer, diluted in 100% oxygen. For transoperative analgesia, brachial plexus block was performed using 2% lidocaine (2 mg/kg). During the surgical procedure, an incision was made in the skin and subcutaneous tissue in the middle third of the left humerus, and detachment of the greater deltoid muscle was performed with a periosteal elevator, followed by excision of the tensor propatagialis. In the ventrodorsal region, circular ligation of the brachial vein, ulnar vein and artery, and median-ulnar nerve was carried out, and disarticulation of the scapulacoracoid-humeral region. Subsequently, abolition of dead space and a myorrhaphy were performed, followed by demorrhaphy. In the immediate post-operative period, morphine (5 mg/kg), meloxicam (0.1 mg/kg), and enrofloxacin (10 mg/kg) were administered intramuscularly. The patient was discharged from the hospital 6 h after the end of the surgical procedure.Discussion: Interest in the conservation of wild birds is one of the causes of the increased demand for anesthetic and surgical procedures in these species. However, it is a challenge for professionals in the field. The use of analgesics is recommended for reasons of well-being, but also because of the possibility of reducing the concentration of inhalational anesthetics in surgical procedures. Ketamine associated with midazolam promotes sufficient sedation and muscle relaxation in the patient, enabling safe preoperative management, in addition to reducing the amount of inhaled anesthetics used during the transoperative period. Isofluorane promotes safe general anesthesia for birds and has an advantage over injectable drugs, as it provides better dynamic control of anesthetic depth in these species. The brachial plexus block performed is a simple procedure that promotes quality anesthesia and analgesia in the perioperative period. The choice for amputation was due to the absence of musculature for closure, severe skin, muscle, and bone devitalization, and the infectious process in the region, factors that would prevent osteosynthesis. Although amputation through the bone is preferable, the disarticulation technique was used due to the absence of a healthy proximal humeral fragment. The patient’s death can be explained by the poor nutritional status the bird was in, as it presented an open fracture with severe contamination, a concomitant injury that occurred during the possible trauma, and the excessive time between the day of the trauma and the day of medical attendance. However, the surgical and anesthetic procedures were adequate and satisfactory for the patient. The importance of identifying and treating diseases secondary to contaminated fractures in these species is emphasized. Keywords: bird, avian medicine, fauna, lesions, recovery. Título: Fratura de úmero em uma curicaca (Theristicus caudatus) - manejo anestésico e cirúrgico Descritores: aves, medicina aviária, fauna, lesões, recuperação

Self-Emulsifying Formulations to Increase the Oral Bioavailability of 4,6,4′-Trimethylangelicin as a Possible Treatment for Cystic Fibrosis

4,6,4'-trimethylangelicin (TMA) is a promising pharmacological option for the treatment of cystic fibrosis (CF) due to its triple-acting behavior toward the function of the CF transmembrane conductance regulator. It is a poorly water-soluble drug, and thus it is a candidate for developing a self-emulsifying formulation (SEDDS). This study aimed to develop a SEDDS to improve the oral bioavailability of TMA. Excipients were selected on the basis of solubility studies. Polyoxyl-35 castor oil (Cremophor (R) EL) was proposed as surfactant, diethylene glycol-monoethyl ether (Transcutol (R) HP) as cosolvent, and a mixture of long-chainmono-,di-, and triglycerides (Maisine (R) CC) or medium-chain triglycerides (Labrafac (TM) lipophile) as oil phases. Different mixtures were prepared and characterized by measuring the emulsification time, drop size, and polydispersity index to identify the most promising formulation. Two formulations containing 50% surfactant (w/w), 40% cosolvent (w/w), and 10% oil (w/w) (Maisine (R) CC or Labrafac (TM) lipophile) were selected. The results showed that both formulations were able to self-emulsify, producing nanoemulsions with a drop size range of 20-25 nm, and in vivo pharmacokinetic studies demonstrated that they were able to significantly increase the oral bioavailability of TMA. In conclusion, SEEDS are useful tools to ameliorate the pharmacokinetic profile of TMA and could represent a strategy to improve the therapeutic management of CF

Investigations Using Albumin Binders to Modify the Tissue Distribution Profile of Radiopharmaceuticals Exemplified with Folate Radioconjugates

Introducing an albumin-binding entity into otherwise short-lived radiopharmaceuticals can be an effective means to improve their pharmacokinetic properties due to enhanced blood residence time. In the current study, DOTA-derivatized albumin binders based on 4-(p-iodophenyl)butanoate (DOTA-ALB-1 and DOTA-ALB-3) and 5-(p-iodophenyl)pentanoate entities (DOTA-ALB-24 and DOTA-ALB-25) without and with a hydrophobic 4-(aminomethyl)benzoic acid (AMBA) linker unit, respectively, were synthesized and labeled with lutetium-177 for in vitro and in vivo comparison. Overall, [177Lu]Lu-DOTA-ALB-1 demonstrated ~3-fold stronger in vitro albumin-binding affinity and a longer blood residence time (T50%IA ~8 h) than [177Lu]Lu-DOTA-ALB-24 (T50%IA ~0.8 h). Introducing an AMBA linker enhanced the albumin-binding affinity, resulting in a T50%IA of ~24 h for [177Lu]Lu-DOTA-ALB-3 and ~2 h for [177Lu]Lu-DOTA-ALB-25. The same albumin binders without or with the AMBA linker were incorporated into 6R- and 6S-5-methyltetrahydrofolate-based DOTA-conjugates (177Lu-RedFols). Biodistribution studies in mice performed with both diastereoisomers of [177Lu]Lu-RedFol-1 and [177Lu]Lu-RedFol-3, which comprised the 4-(p-iodophenyl)butanoate moiety, demonstrated a slower accumulation in KB tumors than those of [177Lu]Lu-RedFol-24 and [177Lu]Lu-RedFol-25 with the 5-(p-iodophenyl)pentanoate entity. In all cases, the tumor uptake was high (30–45% IA/g) 24 h after injection. Both diastereoisomers of [177Lu]Lu-RedFol-1 and [177Lu]Lu-RedFol-3 demonstrated high blood retention (3.8–8.7% IA/g, 24 h p.i.) and a 2- to 4-fold lower kidney uptake than the corresponding diastereoisomers of [177Lu]Lu-RedFol-24 and [177Lu]Lu-RedFol-25, which were more rapidly cleared from the blood (<0.2% IA/g, 24 h after injection). Kidney retention of the 6S-diastereoisomers of all 177Lu-RedFols was consistently higher than that of the respective 6R-diastereoisomers, irrespective of the albumin binder and linker unit used. It was demonstrated that the blood clearance data obtained with 177Lu-DOTA-ALBs had predictive value for the blood retention times of the respective folate radioconjugates. The use of these albumin-binding entities without or with an AMBA linker may serve for fine-tuning the blood retention of folate radioconjugates and also other radiopharmaceuticals and, hence, optimize their tissue distribution profiles. Dosimetry estimations based on patient data obtained with one of the most promising folate radioconjugates will be crucial to identify the dose-limiting organ, which will allow for selecting the most suitable folate radioconjugate for therapeutic purposes.ISSN:2072-669