Sweeter and stronger: Enhancing sweetness and stability of the single chain monellin MNEI through molecular design

Sweet proteins are a family of proteins with no structure or sequence homology, able to elicit a sweet sensation in humans through their interaction with the dimeric T1R2-T1R3 sweet receptor. In particular, monellin and its single chain derivative (MNEI) are among the sweetest proteins known to men. Starting from a careful analysis of the surface electrostatic potentials, we have designed new mutants of MNEI with enhanced sweetness. Then, we have included in the most promising variant the stabilising mutation E23Q, obtaining a construct with enhanced performances, which combines extreme sweetness to high, pH-independent, thermal stability. The resulting mutant, with a sweetness threshold of only 0.28 mg/L (25 nM) is the strongest sweetener known to date. All the new proteins have been produced and purified and the structures of the most powerful mutants have been solved by X-ray crystallography. Docking studies have then confirmed the rationale of their interaction with the human sweet receptor, hinting at a previously unpredicted role of plasticity in said interactio

Intravascular Ultrasound in the Detection of Bridging Stent Graft Instability During Fenestrated and Branched Endovascular Aneurysm Repair Procedures: A Multicentre Study on 274 Target Vessels

Objective: The use of intravascular ultrasound (IVUS) reduces contrast medium use and radiation exposure during conventional endovascular aneurysm repair (EVAR). The aim of this study was to evaluate the safety and efficacy of IVUS in detecting bridging stent graft (bSG) instability during fenestrated and branched EVAR (F/B-EVAR). Methods: This was a prospective observational multicentre study. The following outcomes were evaluated: (1) technical success of the IVUS in each bSG, (2) IVUS findings compared with intra-operative angiography, (3) incidence of post-operative computed tomography angiography (CTA) findings not detected with IVUS, and (4) absence of IVUS related adverse events. Target visceral vessel (TVV) instability was defined as any branch or fenestration issues requiring an additional manoeuvre or re-intervention. Any IVUS assessment that detected stenosis, kinking, or any geometric TVV issue was considered to be branch instability. All procedures were performed in ad hoc hybrid rooms. Results: Eighty patients (69% males; median age 72 years; interquartile range 59, 77 years) from four aortic centres treated with F/B-EVAR between January 2019 and September 2021 were included: 70 BEVAR (21 off the shelf; 49 custom made), eight FEVAR (custom made), and two F/B-EVAR (custom made), for a total of 300 potential TVVs. Two TVVs (0.7%) were left unstented and excluded from the analysis. The TVVs could not be accessed with the IVUS catheter in seven cases (2.3%). Furthermore, 17 (5.7%) TVVs could not be examined due to a malfunction of the IVUS catheter. The technical success of the IVUS assessment was 91.9% (274/298), with no IVUS related adverse events. Seven TVVs (2.5%) showed signs of bSG instability by means of IVUS, leading to immediate revisions. The first post-operative CTA at least 30 days after the index procedure was available in 268 of the 274 TVVs originally assessed by IVUS. In seven of the 268 TVVs (2.6%) a re-intervention became necessary due to bSG instability. Conclusion: This study suggests that IVUS is a safe and potentially valuable adjunctive imaging technology for intra-operative detection of TVV instability. Further long term investigations on larger cohorts are required to validate these promising results and to compare IVUS with alternative technologies in terms of efficiency, radiation exposure, procedure time, and costs

BAG3 protein regulates stress- induced apoptosis in normal and neoplastic leukocytes

Co-chaperone proteins that share the Bcl-2-associated athanogene (BAG) domain are characterized by their interaction with a variety of partners, such as heat shock proteins (Hsp), steroid hormone receptors, Bcl-2, Raf-1 and others, involved in regulating protein folding and a number of cellular processes, including proliferation and apoptosis. Among BAG family members there is BAG3, also known as CAIR-1 or Bis. BAG3 forms a complex with Hsp70,1,2,4,6 a protein able to modulate apoptosis by interfering with cytochrome c release, apoptosome assembly and other events in the death process. In addition, BAG3 polypeptide binds to phospholipase C-g (PLC-g)4 or Bcl-2 protein.3,5 Due to such interaction with more than one apoptosis-modulating factor, BAG3 can participate in apoptosis regulation. Indeed, its hyperexpression can decrease apoptosis induced via Bax or Fas in the human epithelial cell line HeLa3 or by IL-3 deprivation in the murine hematopoietic cell line 32D.5 Furthermore, we recently showed that BAG3 downmodulation enhances the apoptotic response to chemotherapy in human primary B chronic lymphocytic leukemia cell

Intramural aortic hematoma: no flap no warning?

We report a case of type A intramural aortic hematoma (IMH) occurred in a 78 years old female. The clinical scenario (medical history of hypertension, severe substernal chest pain, early diastolic decrescendo murmur as for aortic insufficiency), the laboratory results (no significant troponin level), ECG and transthoracic echocardiography findings (no signs of myocardial ischemia) shifted the initial diagnostic suspicion from acute coronary syndrome to the acute aortic syndrome (AAS) and triggered further imaging tests. Computed tomography revealed an aneurismatic dilatation with thickening of the wall of the ascending aorta without intimal flap. No particular “warning message” for evidence of AAS was sent to the clinician on call. Subsequently, due to the persisting high clinical suspicion transesophageal echocardiography (TEE) was performed. TEE confirmed the aneurysm of the ascending aorta and highlighted an extended and marked aortic wall thickness, consisting with the diagnosis of type A IMH. Patient underwent urgent cardiac surgery that confirmed the diagnosis

Salerno Quadrante. N.1-3 (1955)

1 (giugno 1955): Guglielmo Longo, Ospedali, esigenza prima del Mezzo giorno, P. 3 ; Giuseppe Lanocita, Attualità della questione demaniale e suoi aspetti nel comune di Eboli, P. 9 ; Bilancio di un disastro: L'alluvione in cifre, P. 11 ; Alessandro Pinto, Canti popolari cilentani, P. 17 ; Giovanni Capasso, Poesie inedite, P. 18 ; Francesco Franco. S. Pietro al Tanagro, il paese dalle tovaglie di terra, P. 19 ; Antonio De Angelis, Scafati, cittadina di provincia, P. 23 ; Enzo Barba, Matteo Luciani, P. 25 ; Augusto Visconti, Curiosità e irrequietezza in tre giovani pittori salernitani: D'Agosto, Gentile, Della Monica, P. 28 ; II Centro di cultura Citta di Salerno, P. 29 ; Recensioni, P. 32- 40 ; La resistenza salernitana (fuori testo).2-3 (dicembre 1955): Ugo Renna, Viaggio nel Cilento, P. 3 ; Francesco Franco, La crisi tessile e Ie M.C.M. Fratte-Pellezzano, P. 14 ; Giuseppe Tortorella, II problema del Porto (intervista), P. 23 ; Guglielmo Longo, Difendiamo l'industria salernitana, P. 27 ; Enzo Barba, Errico de Marinis e il "socialismo demariniano, P. 33 ; Giuseppe Lanocita, Attualità della questione demaniale e suoi aspetti nel comune di Eboli, P. 43 ; Giuseppe A. Leone, Pietà per Crocco il brigante (poesia), p. 52 ; Gianni Nunziante, Titoli di proprietà immobiliare al portatore nella pratica medievale salernitana, P. 53 ; Mario Carotenuto, Olga Napoli nella pittura contemporanea (fuori testo)

Prevention of Recurrent Benign Paroxysmal Positional Vertigo: The Role of Combined Supplementation with Vitamin D and Antioxidants

Benign paroxysmal positional vertigo (BPPV) usually has a favorable course, although it is possible to observe BPPV with a high recurrence rate. Previous studies suggested that vitamin D deficiency might affect BPPV recurrences, and oxidative stress might play a complementary role in BPPV pathogenesis. This multicentric trial aimed to evaluate the effectiveness of oral nutritional supplementation with a compound of alpha-lipoic acid, Carnosine, and Zinc (LICA (R) (Difass International, Coriano (RN), Italy)), vitamins of group B and vitamin D in preventing BPPV recurrences. A total of 128 patients with high recurrence-BPPV were randomized in three arms: Arm 1 consisted of subjects with "insufficient" or "deficient" vitamin D blood levels, treated with daily oral supplementation of LICA (R), vitamins of group B and vitamin D3 (800 UI), Arm 2 included BPPV subjects with "sufficient" vitamin D who did not receive any nutritional support, and Arm 3 included subjects with a "sufficient" serum concentration of vitamin D who received supplementation with a compound of LICA (R) and Curcumin. After six months of follow-up, a significant reduction of BPPV relapses compared to the baseline was found only in Arm 1 (-2.32, 95% CI: 3.41-1.62, p-value < 0.0001). Study results suggested that oral nutritional supplementation with vitamin D3 plus antioxidants can prevent relapses in patients suffering from high recurrence-BPPV

Comparison of germinal center markers CD10, BCL6 and human germinal center-associated lymphoma (HGAL) in follicular lymphomas

<p>Abstract</p> <p>Background</p> <p>Recently, human germinal center-associated lymphoma (HGAL) gene protein has been proposed as an adjunctive follicular marker to CD10 and BCL6.</p> <p>Methods</p> <p>Our aim was to evaluate immunoreactivity for HGAL in 82 cases of follicular lymphomas (FLs) - 67 nodal, 5 cutaneous and 10 transformed - which were all analysed histologically, by immunohistochemistry and PCR.</p> <p>Results</p> <p>Immunostaining for HGAL was more frequently positive (97.6%) than that for BCL6 (92.7%) and CD10 (90.2%) in FLs; the cases negative for bcl6 and/or for CD10 were all positive for HGAL, whereas the two cases negative for HGAL were positive with BCL6; no difference in HGAL immunostaining was found among different malignant subtypes or grades.</p> <p>Conclusions</p> <p>Therefore, HGAL can be used in the immunostaining of FLs as the most sensitive germinal center (GC)-marker; when applied alone, it would half the immunostaining costs, reserving the use of the other two markers only to HGAL-negative cases.</p

Helsinki-Vantaan lentoaseman tilannekuvakeskus : Häiriö- ja poikkeamatilanteiden eteneminen lentoasemalla

Tämän opinnäytetyön tavoitteena oli selvittää, miten Finavian ylläpitämällä Helsinki-Vantaa lentoasemalla tapahtuvat häiriö- ja poikkeamatilanteet vaikuttavat lentoasemalla toimiviin Finavian omiin organisaatioihin sekä lentoasemalla toimiviin viranomaisiin. Häiriö- ja poikkeamatilanteella tarkoitetaan lentoaseman normaaliin toimintaan häiritsevästi vaikuttavaa tapahtumaa, esimerkiksi sähkökatkoa. Työ tehtiin Helsinki-Vantaa lentoaseman tilannekuvakeskuksen päällikön pyynnöstä. Tilannekuvakeskuksessa huomattiin, että vaikka häiriö- ja poikkeamatilanteessa toiminta eri tahojen kanssa on ollut kitkatonta ja sujuvaa, ei toisen organisaation sisällä tapahtuvasta toiminnasta ollut kuvaa. Työn avulla selvitettiin, onko häiriö- tai poikkeamatilanteella vaikutusta eri organisaatioiden ja viranomaisten toimintaan. Opinnäytetyö auttaa rakentamaan kokonaiskäsitystä poikkeamatilanteiden aiheuttamasta toiminnasta koko lentoaseman alueella. Tätä kautta voidaan myös lisätä ymmärrystä eri organisaatioiden ja viranomaisten välillä. Opinnäytetyö toteutettiin yhteistyössä Helsinki-Vantaa lentoaseman tilannekuvakeskuksen kanssa. Työn edetessä rakennetta muokattiin yhteistyössä tilaajan kanssa niin, että se palvelisi mahdollisimman tarkoituksenmukaisesti eri organisaatioita. Työ toteutettiin tekemällä laadullinen tutkimus, jonka runkona oli puolistrukturoitu haastattelu. Haastatteluita kertyi yhteensä 19 kappaletta ja haastateltavia 21. Haastateltavina olivat Finavian eri organisaatioiden johtajia tai päälliköitä ja lentoaseman toimintaan liittyvien viranomaisten lentoaseman toimipisteiden päälliköt. Työstä rajattiin pois kaupalliset yritykset, koska haastatteluiden määrä olisi kasvanut liian suureksi. Lentoaseman tilannekuvakeskus on luonut useita valmiita toimintamalleja erilaisiin häiriö- ja poikkeamatilanteisiin. Tilannekuvakeskuksen päällikkö valitsi näistä häiriö- ja poikkeamatilanteista ne, jotka ovat todennäköisiä tai merkittäviä ja vaikuttavat haitallisesti lentoaseman toimintaan. Erilaisia häiriö- ja poikkeamatilanteita valikoitui 17 kappaletta. Näiden tilanteiden vaikutuksia ja toimintamalleja käsiteltiin haastatteluissa. Haastatteluissa saatu informaatio liitettiin tilannekuvakeskuksen toimintamalleihin ja luotiin jokaiseen valittuun poikkeamatilanteeseen kronologinen kuvaus eri organisaatioiden toiminnasta. Opinnäytetyöstä on myöhemmin tarkoitus tehdä pelkistetympi käsikirja Finavian ja viranomaisten käyttöön.The aim of this study was to find out how to Finavia’s Helsinki-Vantaa airport take place in crisis and emergency situations and how they affecting operating at the airport Finavia's own organizations as well as authorities operating at the airport. The work was done at the request of the Head of the Helsinki-Vantaa airport operation center. The airport operation center noted that although the crisis and emergency situations operation with various parties has been smooth, but nobody didn’t have a picture how these crisis and emergency situations was handled in the another organizations. The work purpose was to find out whether the fault or deviation situation could affect the functioning of the various organizations and public authorities. The thesis helps to build the overall understanding of the actions caused by the deviation of situations throughout the airport. This period may also increase the understanding of the different organizations and authorities. The research was conducted in cooperation with the Helsinki-Vantaa airport operation center. As work progresses, the structure was modified in cooperation with the client so that it would serve as appropriately as possible the different organizations. The work was carried out by qualitative research, whose backbone was the semi-structured interview. Interviews were a total of 19 tracks and 21 interviewees were interviewed leaders or managers in different organizations and Finavia's airport activities related to airport authorities, heads of offices. Work were excluded trading companies, because the number of interviews had grown too large. The airport operation center has created a number of ready-made models for different crisis and emergency situations. Head of the Centre chose a snapshot of the crisis and emergency situations, those who are likely or significant and adversely affect the operation of the airport. 17 various types of crisis and emergency situations was selected. Effects and models of these situations addressed in the interviews. The information obtained in the interviews attached a airport operation center’s operational models and was created for each selected deviation situation chronological description of the activities of various organizations. The thesis is later to be made simpler manual for use by Finavia and the authorities

Echocardiography in patients with hypertrophic cardiomyopathy: usefulness of old and new techniques in the diagnosis and pathophysiological assessment

Hypertrophic cardiomyopathy (HCM) is one of the most common inherited cardiomyopathy. The identification of patients with HCM is sometimes still a challenge. Moreover, the pathophysiology of the disease is complex because of left ventricular hyper-contractile state, diastolic dysfunction, ischemia and obstruction which can be coexistent in the same patient. In this review, we discuss the current and emerging echocardiographic methodology that can help physicians in the correct diagnostic and pathophysiological assessment of patients with HCM