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OBJECTIVE: Transit-time flow measurement (TTFM) represents a valid tool in the assessment of the quality of the anastomosis during coronary artery bypass graft (CABG). Nevertheless, a high variability limits its standardized use, lacking univocally accepted cut-off flow values. Our study analyzes TTFM data collected from a study population that underwent off-pump CABG (OP-CABG), with the aim to differentiate into subgroups according to the presence of diabetes mellitus. PATIENTS AND METHODS: Patients referred to the Cardiovascular Unit of S. Michele Hospital (Caserta, Italy) for coronary artery disease (CAD) and underwent OP-CABG between January 2015 and December 2019 were enrolled, and intraoperative TTFMs data were recruited and evaluated. Mean graft flow (MGF) and pulsatility index (PI) values were collected and analyzed. RESULTS: The study population was composed of 342 patients who underwent OP-CABG with TTFM data regarding 824 grafts. Diabetic patients shared a higher cardiovascular risk profile. The TTFM assessment showed better results for the use of the arterial grafts in diabetic patients, especially for those insulin-dependent; conversely, venous grafts showed worse data with lower MGF and higher PI values. In particular, the anastomoses of the saphenous vein graft with marginal obtuse (MO) coronary artery showed worse MGF results in the insulin-dependent rather than normoglycemic subgroup (28.66 vs. 38.44, p=0.003). CONCLUSIONS: Diabetic patients, especially in the insulin-dependent subgroups, have demonstrated lower MGF and higher PI values collected from venous anastomoses with, conversely, inverse results from the arterial one. These results might be correlated to an altered biological adaptability caused by the effects of the diabetic endocrine disorder.

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In Western countries, calcific aortic valve stenosis (CAS) is widely common, representing the third cause of death among cardiovascular diseases (CVD). The burden of CAS is high, with an increasing prevalence rate related to age. An efficient medical treatment, according to guidelines, lacks to prevent the development and to reduce the progression of CAS. In this context, due to the aging population and the lack of effective medical management, the prevalence is expected to double-triple within the next decades. In our review, we aim to provide an overview of the underlying mechanisms of pathogenesis and the current state of the art regarding pathophysiological insights and novel potential therapeutic targets.

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INTRODUCTION: Ventricular septal defect (VSD) is one of the mechanical complications of acute myocardial infarction (MI), whose incidence has been decreasing throughout the years because of the emergence of different reperfusion therapy strategies. METHODS: We present a series of seven patients who underwent surgery for post-MI VSD repair in our institution in the period between March 2020 and June 2021. DISCUSSION: During the recent SARS-COV2 pandemic, time to hospital admission increased due to patients being overcautious out of fear of exposing themselves to COVID-19. The increased time to hospital admission, with associated late reperfusion therapy and delayed PCI, is closely related to an augmented incidence of post-myocardial infarction mechanical complications such as ventricular septal defects. For this reason, we witnessed an increase in the incidence of post-MI VSD. CONCLUSION: Fear of exposure to SARS-COV2 in the medical environment was a major source of concern for all our patients. The target of hospital policy should be to reassure patients of freedom from COVID in the emergency department and cardiac wards in order to prevent such dreadful complications.

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Anomalous aortic origin of a coronary artery (AAOCA) is a rare pathology that may cause episodic ischemia owing to possible vessel compression during systolic expansion of the aortic root. This anomaly can lead to myocardial infarction, malignant arrhythmias and sudden cardiac death (SCD). Several surgical techniques have been described; however, there are no defined guidelines regarding the treatment of AAOCA. We report the case of a 47-year-old woman with ectopic origin of the right coronary artery (RCA) from the left sinus of Valsalva, with an interarterial course of the proximal segment of the artery, running between the aorta and the pulmonary trunk. Revascularization was accomplished by harvesting the right internal mammary artery (RIMA) and anastomosing it to the anomalous RCA, given the small portion of the RCA following an intramural course and our familiarity with the procedure. The RCA was ligated proximal to the anastomosis to avoid the string sign phenomenon. This procedure is safe and fast and can be considered an alternative to coronary reconstruction.

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Results: The results highlighted that 40 laboratories fall into the "low risk" and the remaining 2 into the "moderate risk" category. Conclusions: Labs with risk factors are a minority. These were properly identified using the proposed methodology. Background and aim: Biomedical research in academic settings is an important issue for Public Health and Environment protection. As workplaces, the facilities for research expose their personnel to different hazards and health risks. The University of L'Aquila (Italy) carried out a field study aimed at creating and applying a checklist intended for laboratory staff. Methods: The proposed checklist was derived from the procedure illustrated in the Appendix (procedure followed for the identification of a numerical index of biological risk for university facilities) and consists of 9 items. The study was conducted in 42 laboratories.

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Thymidine phosphorylase (TP) is an enzyme that is up-regulated in a wide variety of solid tumors, including breast and colorectal cancers. It is involved in tumor growth and metastasis, for this reason it is one of the key enzyme to be inhibited, in an attempt to prevent tumor proliferation. However, it also plays an active role in cancer treatment, through its contribution in the conversion of the anti-cancer drug 5-fluorouracil (5-FU) to an irreversible inhibitor of thymidylate synthase (TS), responsible of the inhibition of the DNA synthesis. In this work, the intrinsic TP fluorescence has been investigated for the first time and exploited to study TP binding affinity for the unsubstituted 5-FU and for two 5-FU derivatives, designed to expose this molecule on liposomal membranes. These molecules were obtained by functionalizing the nitrogen atom with a chain consisting of six (1) or seven (2) units of glycol, linked to an alkyl moiety of 12 carbon atoms. Derivatives (1) and (2) exhibited an affinity for TP in the micromolar range, 10 times higher than the parent compound, irrespective of the length of the polyoxyethylenic spacer. This high affinity was maintained also when the compounds were anchored in liposomal membranes. Experimental results were supported by molecular dynamics simulations and docking calculations, supporting a feasible application of the designed supramolecular lipid structure in selective targeting of TP, to be potentially used as a drug delivery system or sensor device.

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The Trp53 gene is the most frequently mutated gene in all human cancers. Its protein product p53 is a very powerful transcription factor that can activate different biochemical pathways and affect the regulation of metabolism, senescence, DNA damage response, cell cycle and cell death. The understanding of its function at the molecular level could be of pivotal relevance for therapy. Investigation of long-range intra- and interdomain communications in the p53 tetramer-DNA complex was performed by means of an atomistic model that included the tetramerization helices in the C-terminal domain, the DNA-binding domains and a consensus DNA-binding site of 18 base pairs. Nonsymmetric dynamics are illustrated in the four DNA-binding domains, with loop L1 switching from inward to outward conformations with respect to the DNA major groove. Direct intra- and intermonomeric long-range communications between the tetramerization and DNA-binding domains are noted. These long-distance conformational changes link the C terminus with the DNA-binding domain and provide a biophysical rationale for the reported functional regulation of the p53 C-terminal region. A fine characterization of the DNA deformation caused by p53 binding is obtained, with 'static' deformations always present and measured by the slide parameter in the central thymine-adenine base pairs; we also detect 'dynamic' deformations switched on and off by particular p53 tetrameric conformations and measured by the roll and twist parameters in the same base pairs. These different conformations can indeed modulate the electrostatic potential isosurfaces of the whole p53-DNA complex. These results provide a molecular/biophysical understanding of the evident role of the C terminus in post-translational modification that regulates the transcriptional function of p53. Furthermore, the unstructured C terminus is able to facilitate contacts between the core DNA-binding domains of the tetramer.

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OBJECTIVES: The oral cavity may represent a site of colonization by antibiotic-resistant bacteria, such as methicillin-resistant staphylococci (MRS). To define the prevalence of staphylococci and MRS in the oral cavity, an observational study was carried out in the city of Bari (Italy). METHODS: Sixty subjects were asked to provide oral samples and a questionnaire about risk factors of colonization by MRS. An enrichment medium specific for staphylococci was used for the isolation. RESULTS: Swabs and corresponding questionnaires were available from 36 out of 60 patients. Staphylococci were isolated from seven out of 36 samples (prevalence 19.4%). Among the seven staphylococcal isolates, three were Staphylococcus aureus, and one strain, belonging to S. epidermidis species, was found to be MR (1.7%). No methicillin-resistant S. aureus were isolated. Five out of seven staphylococcal isolates exhibited resistance to more than two classes of non-beta-lactams antimicrobials. None of the risk factors analysed correlated with the status of MRS carriers, except the presence of oral disease. CONCLUSIONS: The results underline the potential role of the oral cavity as a reservoir of staphylococci.

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Water buffalo (Bubalus bubalis) are affected by high rates of embryonic mortality and abortion related to infectious diseases and non-infectious factors. A number of viral and bacterial infections have been associated with reproductive failure, but there is limited information on the role of chlamydial infections. In order to investigate the presence and the role of Chlamydiaceae in water buffalo a retrospective study was performed in a herd with a history of reproductive failure. During an 11-month period, the pregnant heifers suffered an abortion rate of 36.8% between the 3rd and 7th month of pregnancy. Antibodies to Chlamydiaceae were detected in 57% of the aborted cows, and in 0% of the overtly healthy cows used as control. By a nested-PCR assay, three of 14 vaginal swabs from aborted animals tested positive for Chlamydophila agents and, additionally, three out of seven aborted fetuses tested positive for Chlamydophila spp., with two being co-infections by Cp. abortus and Cp. pecorum and one being characterised as Cp. abortus. Sequence analysis of the amplicons confirmed the results of the nested-PCR. The presence of anti-Chlamydiaceae antibodies in more than half of the aborting animals (P<0.002) and the detection of Chlamydophila agents in several fetal organs and in the vaginal swabs are consistent with the history of abortions observed in the herd and suggest an abortifacient role by Chlamydophila spp. in water buffalo (B. Bubalis) herds.

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AIMS: To compare several methods for detection of methicillin resistance in Staphylococcus aureus isolates from food. METHODS AND RESULTS: Two hundred S. aureus isolates from food of animal origin were screened for methicillin resistance by a PCR assay specific for the mecA gene, an oxacillin agar screen test and a cefoxitin disk diffusion test. Six out of 200 strains (3%) were found to be methicillin-resistant Staphylococcus aureus (MRSA) by PCR. The oxacillin agar screen test detected only one of the MRSA isolates (sensitivity of 16.7%) and mischaracterized three additional strains as MRSA (specificity of 98.45%). None of the MRSA strains was detected by the cefoxitin test (sensitivity of 0%), while 15 methicillin-susceptible S. aureus (MSSA) strains were misclassified as resistant (specificity of 92.3%). Fifteen MSSA strains displayed a beta-lactamase hyperproducer-like phenotype. The six MRSA (mecA-positive) strains resembled the characteristics of heteroresistant strains. CONCLUSIONS: As MRSA of animal origin may display atypical phenotypes, PCR appears to be more reliable for detection of methicillin resistance in animal strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The study stresses the need for implementing the methods of screening S. aureus from food of animal origin for methicillin resistance.

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Molecular dynamics (MD) simulations and circular dichroism (CD) experiments were carried out on aqueous temporin A and L, two short peptides belonging to an interesting class of natural substances known to be active mainly against Gram-positive/negative bacteria and fungi. Experimental results indicate the higher propensity of temporin L, with respect to temporin A, in forming alpha-helical structures. These results were revisited by long-timescale MD simulations, in which their alpha-helical propensity was investigated in the absence of trifluoroethanol. Results clearly show the higher stability of alpha-helix conformations in temporin L; moreover, an interestingly strong mechanical analogy emerges since both temporins show the same residue interval (from 7 to 10) as the most energetically accessible for alpha-helix formation. Such studies provide some intriguing structural and mechanical evidence that may help in better understanding and rationalizing the conformational behaviour of temporins in water solution and, ultimately, the inner principles of their microbial targets selectivity and mechanism of action at the level of cell membranes.

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In a recent paper [M. D'Alessandro, M. D'Abramo, G. Brancato, A. Di Nola, and A. Amadei, J. Phys. Chem. B 106, 11843 (2002)] we showed how to combine molecular dynamics simulations with the quasi-Gaussian entropy theory, in order to model the statistical mechanics and thermodynamics of ionic (water) solutions. In this paper we extend the method to treat nonspherical solutes, describe more thoroughly its theoretical basis and apply it to a set of more complex solute molecules in water (i.e., water, methane, ethane, methanol, and ethanol). Results show that this approach can really provide an excellent theoretical description of solute-solvent systems over a wide range of temperatures.