SYNTHESIS AND COMFORMATIONAL ANALYSIS OF PEPTIDES ANALOGUES OF THE CENTRAL SEQUENCE OF LULIBERIN B-TURN INVESTIGATION BY CHARGE TRANSFER COMPLEXES

IN ORDER TO VISUALIZE SPECIFIC SIDE CHAIN-SIDE CHAIN INTERACTIONS IN PEPTIDES VIA CHARGE TRANSFER COMPLEXES BETWEEN TRP AND NVA(NIC+) WITH THE AIM OF FORMULATING A RATHER SIMPLE WAY TO EVALUATE THE PROBABILITY OF A B-TURN CONFORMATION THREE MODEL TETRAPEPTIDES WERE PREPARED BY THE SOLID PHASE TECHNIQUE: AC-TRP- TYR-X-NVA(NIC+)-NH2.CL- WHERE X STANDS FOR D-ALA, GLY, OR L-ALA, AND REFLECTS A GRADUAL DECREASE OF FOLDING. THESE MOLECULES WERE ANALYSED BY UV-VIS AND 1H-NMR SPECTROSCOPIES. ALL THE THREE ANALOGUES SHOWED A CHARACTERISTIC CHARGE-TRANSFER BAND AS A SHOULDER IN THE LONG WAVE LENGTH REGION OF THE UV-VIS SPECTRA. THE DIFFERENCES IN THE INTENSITY AT 380 NM REVEAL AN INCREASED SIDE CHAIN- SIDE CHAININTERACTION IN THE ORDER OF L-ALA<GLY<D- ALA FOR X. ON THE OTHER HAND, ON THE BASE OF THE NMR DATA IT CAN BE CONCLUDED THAT AN OPEN REVERSE B-TURN OCCURS, OFTHE TYPE II WHEN X=D-ALA AND OF THE TYPE I WHEN X=L-ALA. THE TYPE OF THE TURN IS FURTHER SUPPORTED BY SELECTIVE NOE MEASUREMENTS. IN CONCLUSION SUCH COMPLEXES CAN BE USED AS SELECTIVE CONFORMATIONAL PROBES TO RECOGNIZE SPECIFIC INTERACTIONS AND PROVIDE INFORMATION ABOUT THE STATISTICAL OCCURENCE OF THE FOLDED CONFORMER.ΠΡΟΚΕΙΜΕΝΟΥ ΝΑ ΜΠΟΡΟΥΝ ΝΑ ΔΙΕΡΕΥΝΩΝΤΑΙ ΕΞΕΙΔΙΚΕΥΜΕΝΕΣ ΑΛΛΗΛΕΠΙΔΡΑΣΕΙΣ ΜΕΤΑΞΥ ΠΑΡΑΠΛΕΥΡΩΝ ΑΛΥΣΙΔΩΝ ΣΕ ΠΕΠΤΙΔΙΑ ΔΙΑ ΜΕΣΟΥ ΣΥΜΠΛΟΚΩΝ ΜΕΤΑΦΟΡΑΣ ΦΟΡΤΙΟΥ ΜΕΤΑΞΥ TRPΚΑΙ NVA(NIC+) ΜΕ ΣΚΟΠΟ ΝΑ ΚΑΘΙΕΡΩΘΕΙ ΕΝΑΣ ΜΑΛΛΟΝ ΑΠΛΟΣ ΤΡΟΠΟΣ ΓΙΑ ΤΗΝ ΕΚΤΙΜΗΣΗΤΗΣ ΠΙΘΑΝΟΤΗΤΑΣ ΤΗΣ ΔΙΑΜΟΡΦΩΣΗΣ Β-ΣΤΡΟΦΗΣ ΠΑΡΑΣΚΕΥΑΣΘΗΚΑΝ ΤΡΙΑ ΠΡΟΤΥΠΑ ΤΕΤΡΑΠΕΠΤΙΔΙΑ ΜΕ ΤΗΝ ΤΕΧΝΙΚΗ ΤΗΣ ΣΤΕΡΕΑΣ ΦΑΣΗΣ: AC-TRP- TYR-X-NVA(NIC+)-NH2.CL- ΟΠΟΥ ΤΟ Χ ΕΙΝΑΙ D-ALA, GLY, 'Η L-ALA ΚΑΙ ΑΝΤΙΚΑΤΟΠΤΡΙΖΕΙ ΜΙΑ ΒΑΘΜΙΑΙΑ ΜΕΙΩΣΗ ΤΗΣ ΔΙΠΛΩΣΗΣ. ΑΥΤΑ ΤΑ ΜΟΡΙΑ ΑΝΑΛΥΘΗΚΑΝ ΜΕ ΦΑΣΜΑΤΟΣΚΟΠΙΕΣ ΥΠΕΡΙΩΔΟΥΣ-ΟΡΑΤΟΥ ΚΑΙ ΠΡΩΤΟΝΙΑΚΟΥ ΜΑΓΝΗΤΙΚΟΥ ΣΥΝΤΟΝΙΣΜΟΥ. ΚΑΙ ΤΑ ΤΡΙΑ ΑΝΑΛΟΓΑ ΠΑΡΟΥΣΙΑΣΑΝ ΜΙΑ ΧΑΡΑΚΤΗΡΙΣΤΙΚΗ ΖΩΝΗ ΑΠΟΡΡΟΦΗΣΗΣ ΜΕΤΑΦΟΡΑΣ ΦΟΡΤΙΟΥ ΣΤΗΝ ΜΑΚΡΟΥ ΜΗΚΟΥΣ ΚΥΜΑΤΟΣ ΠΕΡΙΟΧΗ ΤΩΝ ΦΑΣΜΑΤΩΝ ΥΠΕΡΙΩΔΟΥΣ-ΟΡΑΤΟΥ. ΟΙ ΔΙΑΦΟΡΕΣ ΣΤΗΝ ΕΝΤΑΣΗ ΣΤΑ 380 ΝΜ ΑΠΟΚΑΛΥΠΤΟΥΝ ΜΙΑ ΑΥΞΑΝΟΜΕΝΗ ΑΛΛΗΛΕΠΙΔΡΑΣΗ ΜΕΤΑΞΥ ΤΩΝ ΠΑΡΑΠΛΕΥΡΩΝ ΑΛΥΣΙΔΩΝ ΚΑΤΑ ΤΗ ΣΕΙΡΑ L- ALA<GLY<D-ALA ΓΙΑ ΤΟ Χ. ΕΞ'ΑΛΛΟΥ ΜΕ ΒΑΣΗ ΤΑ NMR ΔΕΔΟΜΕΝΑ ΜΠΟΡΕΙ ΝΑ ΕΞΑΧΘΕΙ ΤΟ ΣΥΜΠΕΡΑΣΜΑΟΤΙ ΣΥΜΒΑΙΝΕΙ ΜΙΑ ΑΝΟΙΚΤΗ ΑΝΤΙΣΤΡΟΦΗ Β- ΣΤΡΟΦΗ ΤΟΥ ΤΥΠΟΥ ΙΙ ΟΤΑΝ X=D-ALA ΚΑΙ ΤΟΥ ΤΥΠΟΥ Ι ΟΤΑΝ X=L-ALA. Ο ΤΥΠΟΣ ΤΗΣ ΣΤΡΟΦΗΣ ΥΠΟΣΤΗΡΙΖΕΤΑΙ ΠΕΡΑΙΤΕΡΩ ΜΕ ΕΚΛΕΚΤΙΚΑ ΝΟΕ ΠΕΙΡΑΜΑΤΑ. ΩΣ ΣΥΜΠΕΡΑΣΜΑ ΠΡΟΚΥΠΤΕΙ ΟΤΙ ΤΕΤΟΙΑ ΣΥΜΠΛΟΚΑ ΜΠΟΡΟΥΝ ΝΑ ΧΡΗΣΙΜΟΠΟΙΗΘΟΥΝ ΩΣ ΕΚΛΕΚΤΙΚΟΙ ΜΑΡΤΥΡΕΣ ΤΗΣ ΔΙΑΜΟΡΦΩΣΗΣ ΠΡΟΚΕΙΜΕΝΟΥ ΝΑ ΑΝΑΓΝΩΡΙΣΘΟΥΝ ΕΞΕΙΔΙΚΕΥΜΕΝΕΣ ΑΛΛΗΛΕΠΙΔΡΑΣΕΙΣ ΚΑΙ ΝΑ ΑΠΟΚΤΗΘΟΥΝ ΠΛΗΡΟΦΟΡΙΕΣ ΓΙΑ ΤΗΝ ΣΤΑΤΙΣΤΙΚΗ ΤΟΥ ΔΙΠΛΩΜΕΝΟΥ ΔΙΑΜΟΡΦΩΜΕΡΟΥΣ

Renal cell carcinoma with bilateral synchronous adrenal gland metastases: a case report

INTRODUCTION: Renal cell carcinoma is characterized by its potential of metastasizing widely and to unusual sites, with the metastases occasionally preceding clinical recognition of the primary tumor. Synchronous bilateral adrenal metastases from renal cell carcinoma, without other metastases, are rare and, to our knowledge, only 17 cases have been published in the literature to date. In general, patients with synchronous bilateral adrenal metastases from renal cell carcinoma have a poor prognosis. CASE PRESENTATION: We report a case of right-sided renal cell carcinoma with simultaneous bilateral adrenal metastases in a 58-year-old woman. The primary tumor was localized in the upper and mid pole of the kidney. The diagnosis was established preoperatively by abdominal ultrasound and computed tomography. Surgical treatment consisted of a right radical nephrectomy and bilateral adrenalectomy. Postoperative cortisone acetate replacement was instituted. The pathological findings of the right renal tumor showed clear cell carcinoma and both adrenal tumors showed the same pathology as the right renal tumor. There was no evidence of recurrence after 6 months of follow-up. CONCLUSION: Patients with bilateral synchronous adrenal metastases should be considered to have disseminated metastatic disease. However, good performance status, the presence of paraneoplastic syndrome and the alleviation of refractory pain are important reasons make an urologist to consider radical nephrectomy in renal cell carcinoma patient with metastases

Organization capital, dividends and firm value: international evidence

This study investigates the relationship between organization capital, dividends, and firm value across 61 countries. We find that firms with higher organization capital distribute more dividends. By exploiting changes in the stringency of national labor regulations, we demonstrate that this effect strengthens when labor markets become more flexible. Additionally, we document that the market places a premium on dividend payouts from firms with higher organization capital. Further analysis reveals that this premium differential and the positive organization capital-dividend payouts relationship, are more pronounced in firms and countries marked by substantial agency issues. The robustness of our evidence is affirmed through several endogeneity tests, supporting the agency view of organization capital.</p

Complete Vascular Replacement of the Infrarenal Inferior Vena Cava and Abdominal Aorta during Post-Chemotherapy Retroperitoneal Lymph Node Dissection for a Non-Seminomatous Germ Cell Tumor

Testicular germ cell tumors (TGCTs) are the leading cause of cancer-related death in males between the ages of 20 and 40. In the advanced stages, the combination of cisplatin-based chemotherapy and surgical excision of the remaining tumor can cure many of these patients. Vascular procedures may be required during retroperitoneal lymph node dissection (RPLND) in order to achieve the complete excision of all residual retroperitoneal masses. Careful assessment of pre-operative imaging and the identification of patients who could benefit from additional procedures are important for minimizing peri- and postoperative complications. We report on a case of a 27-year-old patient with non-seminomatous TGCT, who successfully underwent post-chemotherapy RPLND with additional infrarenal inferior vena cava (IVC) and complete abdominal aorta replacement using synthetic grafts

The Prognostic Role of Aortic Stiffness in Patients Hospitalized for an Acute Heart Failure Syndrome

Background: Although impaired arterial function has been associated with adverse prognosis in chronic Heart Failure (HF), its role in Acute HF Syndromes (AHFS) has been little studied. We prospectively investigated the prognostic role of arterial function on mortality and HF Hospitalizations (HHF) in patients with AHFS. Design and Methods: A thorough assessment of arterial function was performed in patients hospitalized for AHFS 24–48 h before discharge and followed-up for 6 months for all-cause death and HHF. MAGGIC risk score was used to evaluate the additive predictive value of vascular biomarkers for clinical events. Results: One-hundred patients were studied; aged 70 ± 11 years, 78% males, 61% had left ventricular ejection fraction ≤40% and 24% ≥50%. Mean aortic Pulse Wave Velocity (PWV) was 11.2 m/s, mean augmentation index 21% and median brachial flow-mediated dilation 3.14%. Higher PWV was associated with all-cause mortality (Hazard Ratio [HR] 1.32 per 1 m/s, p &lt; 0.001) and the combined clinical event of mortality and HHF (HR 1.12 per 1 m/s, p = 0.012) even after adjustment for MAGGIC score. MAGGIC score predicted mortality (HR 3.40 per group increase, Area under Curve [AUC] = 0.741, p = 0.017) in our population; addition of PWV to MAGGIC score increased the predictive accuracy (AUC = 0.911, C-statistic p &lt; 0.01 vs. MAGGIC score alone) for mortality. Conclusion: In these AHFS patients, increased aortic stiffness was independently associated with mortality and further improved the predictive accuracy of an established risk model. Further research is needed to show whether a comprehensive assessment of AHFS patients focusing both on cardiac and vascular function, may improve management and ameliorate prognosis following an AHF hospitalization. •The interaction between the heart and the arteries is a determinant of cardiovascular function. •Increased aortic Pulse Wave Velocity (PWV) predicts mortality in acute heart failure. •Aortic PWV increases predictive accuracy of MAGGIC score

Renin-Angiotensin System Single Nucleotide Polymorphisms Are Associated with Bladder Cancer Risk

The renin-angiotensin system (RAS), besides being a major regulator of blood pressure, is also involved in tumor angiogenesis. Emerging evidence suggests a correlation between the use of pharmacologic RAS inhibitors and a delay in urothelial bladder cancer (BC) progression. However, it is unknown whether RAS gene variants may predispose to the development of BC. This study examined the association of RAS single nucleotide polymorphisms (SNPs) including AT1R rs5186, AT2R rs11091046, REN rs12750834, ANG rs4762, and ANG rs699 with the risk of developing non-invasive BC. Peripheral blood samples from 73 patients with T1 urothelial BC (66 men, seven women) and an equal number of healthy subjects (control group) were collected. The TT genotype of the REN rs12750834 SNP (OR: 2.8 [1.3–6.05], p = 0.008) and to a lesser extent the presence of the T allele (OR: 2.3 [1.2–4.48], p = 0.01) conferred a higher risk of BC. The highest risk for BC within SNP carriers of the RAS system was associated with the presence of the CC genotype (OR: 17.6 [7.5–41.35], p p p < 0.001). In conclusion, these results support the clinical utility of RAS gene SNPs AT2R rs11091046, REN rs12750834, and ANG rs699 in the genetic cancer risk assessment of patients and families with BC

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)