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Butylated hydroxytoluene (BHT) is one of the most commonly used synthetic antioxidants in food, cosmetic, pharmaceutical and petrochemical products. BHT is considered safe for human health, however, its widespread use together with the potential toxicological effects have increased consumers concern about the use of this synthetic food additive. In addition, the estimated daily intake of BHT has been demonstrated to exceed the recommended acceptable threshold. In the present work, using BHT as a case study, the usefulness of computational techniques, such as reverse screening and molecular docking, in identifying protein&ndash, ligand interactions of food additives at the bases of their toxicological effects has been probed. The computational methods here employed have been useful for the identification of several potential unknown targets of BHT, suggesting a possible explanation for its toxic effects. In silico analyses can be employed to identify new macromolecular targets of synthetic food additives and to explore their functional mechanisms or side effects. Noteworthy, this could be important for the cases in which there is an evident lack of experimental studies, as is the case for BHT.

The anticoagulant therapy is widely used to prevent and treat thromboembolic events. Until the last decade, vitamin K antagonists were the only available oral anticoagulants; recently, direct oral anticoagulants (DOACs) have been developed. Since 55% to 95% of DOACs are bound to plasma proteins, the in silico docking and ligand-binding properties of drugs apixaban, betrixaban, dabigatran, edoxaban, and rivaroxaban and of the prodrug dabigatran etexilate to human serum albumin (HSA), the most abundant plasma protein, have been investigated. DOACs bind to the fatty acid (FA) site 1 (FA1) of ligand-free HSA, whereas they bind to the FA8 and FA9 sites of heme-Fe(III)- and myristic acid-bound HSA. DOACs binding to the FA1 site of ligand-free HSA has been validated by competitive inhibition of heme-Fe(III) recognition. Values of the dissociation equilibrium constant for DOACs binding to the FA1 site (ie, calc KDOAC ) derived from in silico docking simulations (ranging between 1.2 × 10-8 M and 1.4 × 10-6 M) agree with those determined experimentally from competitive inhibition of heme-Fe(III) binding (ie, exp KDOAC ; ranging between 2.5 × 10-7 M and 2.2 × 10-6 M). In addition, this study highlights the inequivalence of rivaroxaban binding to mammalian serum albumin. Given the HSA concentration in vivo (~7.5 × 10-4 M), values of KDOAC here determined indicate that the formation of the HSA:DOACs complexes in the absence and presence of FAs and heme-Fe(III) may occur in vivo. Therefore, HSA appears to be an important determinant for DOACs transport.

In recent years, the high throughput and the low cost of next-generation sequencing (NGS) technologies have led to an increase of the amount of (meta)genomic data, revolutionizing genomic research studies. However, the quality of sequencing data could be affected by experimental errors derived from defective methods and protocols. This represents a serious problem for the scientific community with a negative impact on the correctness of studies that involve genomic sequence analysis. As a countermeasure, several alignment and taxonomic classification tools have been developed to uncover and correct errors. In this critical review some of these integrated software tools and pipelines used to detect contaminations in reference genome databases and sequenced samples are reported. In particular, case studies of bacterial contaminations, contaminations of human origin, mitochondrial contaminations of ancient DNA, and cross contaminations are examined.

Haptoglobin related protein (Hpr) is a component of the trypanosome lytic factor (TLF), a complex acting in the innate immune response against African trypanosomes. Like haptoglobin (Hp), Hpr binds hemoglobin (Hb) in the blood, but unlike Hp, Hpr does not bind the CD163 receptor. Moreover, unlike Hp, Hpr retains the

Haptoglobin (Hp) counterbalances the adverse effects of extra-erythrocytic hemoglobin (Hb) by trapping the αβ dimers of Hb in the bloodstream. In turn, the Hp:Hb complexes display Hb-like reactivity. Here, the kinetics of NO dissociation from ferrous nitrosylated Hp:Hb complexes (i.e., Hp1-1:Hb(II)-NO and Hp2-2:Hb(II)-NO, respectively) are reported at pH 7.0 and 20.0 °C. NO dissociation from Hp:Hb(II)-NO complexes has been followed by replacing NO with CO. Denitrosylation kinetics of Hp1-1:Hb(II)-NO and Hp2-2:Hb(II)-NO are biphasic, the relative amplitude of the fast and slow phase being 0.495 ± 0.015 and 0.485 ± 0.025, respectively. Values of k

The aim of the study was to identify the best conditions in iliac sandwich procedure for hypogastric artery preservation during endovascular aneurysm repair, testing different devices, different oversizing (OS) degrees as well as different methods to measure it.Four external iliac devices (16-mm Endurant and 12-mm Aorfix limb extensions; 11- and 13-mm Viabahn endografts) were tested with 2 distinct internal iliac stent grafts (8-mm Advanta V12 and 8-mm Viabahn) inside different proximal silicon iliac limb models (10, 12, 14, 16, and 18 mm), simulating an iliac sandwich procedure for hypogastric preservation. After remodeling all devices in a saline bath at 37°C, the combinations were computed tomography scanned. Gutter size, parallel-stent compression, and inadequate parallel-stent deployment or infolding were recorded. Oversizing between both parallel stents and the iliac limb models were examined in terms of added diameter, perimeter, and area being additionally compared.All three sizing methods (diameter, perimeter, and area) were highly correlated (diameter OS to perimeter and area OS correlation coefficient 0.998 and 0.997, respectively, P 0.001 for both); thus, diameter OS was used for further comparisons. Increasing diameter OS (30%, 30-55%, 55-75%, and75%) showed a significant tendency toward smaller gutters (38.9, 12.2, 5.4, and 2.6 mmIn iliac sandwich procedures, better apposition is usually achieved when using 30-55% diameter OS; higher OS is related to smaller gutters but higher rates of malpositioning and parallel-stent compression. No clear recommendations in material selection can be performed. All sizing methods are highly correlated and predictable.

Two loci for nonsyndromic recessive deafness located on chromosome 21q22.3 have previously been reported, DFNB8 and DFNB10. Recently a gene which encodes a transmembrane serine protease, TMPRSS3 or ECHOS1, was found to be responsible for both the DFNB8 and DFNB10 phenotypes. To determine the contribution of TMPRSS3 mutations in the general congenital/childhood nonsyndromic deaf population we performed mutation analysis of the TMPRSS3 gene in 448 unrelated deaf patients from Spain, Italy, Greece, and Australia who did not have the common 35delG GJB2 mutation. From the 896 chromosomes studied we identified two novel pathogenic mutations accounting for four mutant alleles and at least 16 nonpathogenic sequence variants. The pathogenic mutations were a 1-bp deletion resulting in a frameshift and an amino acid substitution in the LDLRA domain of TMPRSS3. From this and another study we estimate the frequency of TMPRSS3 mutations in our sample as 0.45%, and approximately 0.38% in the general Caucasian childhood deaf population. However, TMPRSS3 is still an important contributor to genetic deafness in populations with large consanguineous families.

Objective The aim of this study is to identify which endograft-parallel stent combinations and which degree of oversizing result in the most adequate fit in a juxtarenal abdominal aneurysmal neck, when using a double or triple parallel-stent (chimney) technique. Methods In vitro silicon, juxtarenal, abdominal aortic aneurysmal neck models of different diameters, with two and three side-branches (simulating both the renal and superior mesenteric arteries), were constructed. Two different endografts of three diameters each, with two or three parallel stents (of 6 mm and 6 mm; or 6 mm, 6 mm, and 8 mm) were tested (Endurant-II endograft [Medtronic Inc, Santa Rosa, Calif] with balloon-expandable BeGraft stent [Bentley InnoMed, Hechingen, Germany] and an Excluder endograft [W. L. Gore and Associates, Flagstaff, Ariz] with self-expanding Viabahn stent [W. L. Gore and Associates]), applying three endograft-oversizing degrees: recommended (15%), excessive (30%), and over-excessive (40%). After remodeling, using the kissing-balloon technique at 37°C (98.6°F), 36 endograft-stent-oversizing models were scanned by computed tomography. The area of the gutters, parallel-stent compression, and main endograft infolding were recorded. Results Increasing oversizing (15%, 30%, and 40%) revealed a nonsignificant propensity toward smaller gutters and similar parallel-stent compression, but it significantly augmented infolding, more in three parallel-stent models (0%, 0%, 67% and 0%, 33%, 83% of cases; P = .015 and .018, for two and three parallel-stent models; n = 36) and mainly for the Excluder-Viabahn combination. The Excluder-Viabahn showed significantly smaller gutters, but with higher stent compression, than Endurant-BeGraft combinations for both two and three parallel stents (8.2 mm 2 , 22.6 mm 2 ; P = .002 and 14.4 mm 2 , 23.3 mm 2 ; P = .009 gutter area; and 18%, 2%; P P = .007 relative stent area compression, respectively). Conclusions Better endograft stent apposition was usually attained when using 30% oversizing during two and three parallel-stent techniques. Higher oversizing was related to nonsignificant smaller gutters but higher rates of infolding. Smaller gutters, but higher stent compression and risk of infolding, were achieved with the Excluder-Viabahn than with the Endurant-BeGraft combination.

Background Most people with mental disorders are not violent. However, the lack of specific studies in this area and recent radical changes in Italy, including the closure of six Forensic Mental Hospitals, has prompted a more detailed investigation of patients with aggressive behaviour. Aims To compare socio-demographic, clinical and treatment-related characteristics of long-term inpatients with a lifetime history of serious violence with controls; to identify predictors of verbal and physical aggressive behaviour during 1-year follow-up. Methods In a prospective cohort study, patients living in Residential Facilities (RFs) with a lifetime history of serious violence were assessed with a large set of standardized instruments and compared to patients with no violent history. Patients were evaluated bi-monthly with MOAS in order to monitor any aggressive behaviour. Results The sample included 139 inpatients, 82 violent and 57 control subjects; most patients were male. The bi-monthly monitoring during the 1-year follow-up did not show any statistically significant differences in aggressive behaviour rates between the two groups. The subscale explaining most of the MOAS total score was aggression against objects, although verbal aggression was the most common pattern. Furthermore, verbal aggression was significantly associated with aggression against objects and physical aggression. Conclusions Patients with a history of violence in RFs, where treatment and clinical supervision are available, do not show higher rates of aggressiveness compared to patients with no lifetime history of violence. Since verbal aggression is associated with more severe forms of aggression, prompt intervention is warranted to reduce the risk of escalation.

Objective To evaluate the efficacy of a novel protocol of ovulation induction for poor responders. Design Prospective, controlled, clinical study. Setting Research institute's reproductive unit. Patient(s) One hundred forty-five infertile women, aged 27–39 years, candidates for assisted reproductive techniques (ART). Intervention(s) Before undergoing ART, 85 patients received clomiphene citrate, high-dose recombinant human FSH, and a delayed, multidose GnRH antagonist, whereas 60 patients underwent a standard long protocol. Main outcome measure(s) Estradiol levels (pg/mL), cancellation rate, oocyte retrieval, embryo score, and fertilization and pregnancy rates. Result(s) Patients undergoing the study protocol obtained lower cancellation rates (4.7% vs. 34%) and higher E 2 levels (945.88 ± 173.2 pg/mL vs. 169.55 ± 45.07 pg/mL), oocyte retrieval (5.56 ± 1.13 vs. 3.36 ± 1.3), and pregnancy (22.2% vs. 15.3%) and implantation rates (13.5% vs. 7.6%) compared with those receiving the long protocol. Age negatively correlated with ovarian response in the latter, whereas the ovarian outcome results were comparable in younger ( 35 yrs) women treated with the study protocol. Conclusion(s) The proposed protocol of ovulation induction can be usefully administered in poor responders as well as in aged woman, probably because the delayed administration of GnRH antagonist prevents its adverse effects on ovarian paracrine activity and on oocyte maturation.

Spatial path in Corsi's test is defined as the ideal line joining the blocks tapped by the Examiner so the difficulty of the spatial path was analysed vis-à-vis the numbers of blocks tapped by the Examiner and the number of times the line criss-crosses itself through the spatial path. During an experiment with two different numbers of blocks and three different numbers of crosses, an analysis of variance showed that both factors, i.e., the number of blocks and the number of crosses, gave significant results. The experiment showed that it is possible to create a series with a decreased number of blocks, but with an increased number of crosses, which was more difficult than a series with a greater number of blocks but with a decreased number of crosses. Despite this, additional significant differences have been found among the series with the same number of blocks and crosses, meaning that the variables examined, although important, do not solve the problem with the complexity of the spatial path. At this stage, the length of the path, measured in millimetres, had to be considered as a further source of variance which could explain the difficulty of the spatial path. The correlation between path length and mean number correct achieved, through a single series of digits utilised in this research, was -.78. This value encourages further research.

The aim of this study was to verify the suitability of antituberculosis (antiTB) drug-resistance surveillance as a tool for tuberculosis (TB) control programmes at local level. A retrospective study reviewing laboratory records and medical records of TB patients referred to Udine Hospital between 1981 and 1995 was analysed. The initial susceptibility pattern for each Mycobacterium tuberculosis isolate was recorded. It was found that between 1981 and 1995, 899 M. tuberculosis strains underwent susceptibility testing for four first-line drugs. Over a period of 15 yrs the annual number of M. tuberculosis strains initially decreased and then stabilized. Overall, 15.3% of the 899 strains showed initial resistance to at least one first-line drug, and 2.8% to two or more first-line drugs. Streptomycin-resistant strains were the most commonly observed (10.8%), with resistance to isoniazid, rifampicin and ethambutal shown to be 6.4, 1.0 and 0.4%, respectively. Multidrug resistant (MDR)-TB was observed in only five cases. An additional four cases eventually developed secondary MDR-TB during the follow-up. The proportion of resistant strains did not vary significantly over time. Recurrent TB disease was significantly associated with resistant strains (odds ratio = 3.59, p0.01). Only one patient had a documented human immunodeficiency virus (HIV)-positive serology. All six patients who developed MDR-TB during or after treatment, were suffering either from chronic alcoholism or from a psychotic disorder. In the study it was shown that recurrent tuberculosis cases, tuberculosis patients with behavioural problems (i.e. alcoholism, psychiatric disorder) and patients presenting with primary resistant Mycobacterium tuberculosis strains are at risk of multidrug-resistant tuberculosis and may thus benefit from the directly observed treatment approach, which has been proposed as a mainstay in tuberculosis control programme strategy.

The dopaminergic system seems to be involved in pain modulation. In a 1983 publication, the administration of a dopaminergic agonist has been proposed as a test able to distinguish migraine from other cephalalgia. In the present study, 123 people were tested, 102 of them being migraine patients and the others being normal subjects. The test showed highly specificity for headache patients when compared to normal subjects, and was highly specific for migraine patients when compared to headache patients. Data are discussed considering the clinical diagnostic value, pathophysiological and therapeutic aspects.

The aim of this study was to determine the value of basal FSH as a predictor of assisted reproduction outcome in womenor=35 years undergoing ovarian stimulation with gonadotrophin-releasing hormone (GnRH) antagonist. A retrospective clinical study was carried out on 83 infertile women, 35-45 years old, divided into three groups according to their day 3 FSH concentration (group A = FSHor=10 mIU/ml, group B = FSH10 and15 mIU/ml, group C = FSH15 mIU/ml). Patients underwent ovarian stimulation with a GnRH-antagonist protocol. Group A women had significantly higher basal inhibin B concentrations (P0.001), lower cancellation rate (P0.001), required a significantly lower dosage of recombinant FSH (P0.0001) and had significantly higher oestradiol concentration under stimulation compared with the other groups (P0.0001). Oocyte and embryo numbers were comparable in all groups, although groups B and C had more low quality embryos compared with group A. The number of metaphase II oocytes and embryos was related to patients' ovarian reserve markers only in group C. Pregnancy and delivery rates were 35 and 22.5% in group A, 22.2 and 16.6% in group B and 5 and 0% in group C. It is concluded that a basal FSH cut-off of 10 mIU/ml seems predictive of ovarian reserve, while basal FSH cut-off of 15 mIU/ml seems predictive of pregnancy potential and probably of oocyte quality.