Foot and ankle measurements on cone beam weightbearing computed tomography.

Over the last years, an increased number of studies have reported the use of cone beam weightbearing computed tomography (WBCT) in the assessment of foot and ankle pathology. This new technology has enabled to overcome the limits inherently related to two-dimensional radiographs (superimposition bias, operator-related bias, rotation bias) and to obtain images reproducing the bones and joints anatomy during physiological standing with a low radiation dose. We performed a review of the current literature to summarize the evidence about the use of 2D or 3D measurements on WBCT images in various foot and ankle conditions. Our aims were to describe measurements proposed so far and to report data on reliability and validity from primary authors.

Prevention and treatment of peri-prosthetic joint infection using surgical wound irrigation.

Over the past decade, the incidence of revision arthroplasty due to infection has increased substantially, often resulting in multiple surgical interventions with variable success rates and poor clinical outcome. Intraoperative wound irrigation has been proposed to reduce bacterial bioburden and contamination, but currently there is no widely accepted recommendation for the use of topical antiseptics, whether as separate molecules or as a mixed solution. We reviewed studies regarding the use of intraoperative topical antiseptics, their security profile and efficacy in preventing and treating infections of orthopedic implants and introduced a possible combination that may prove valuable in the future.

A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis.

OBJECTIVE: To conduct a long-term, prospective, randomized controlled trial evaluating rituximab (RTX) therapy for severe mixed cryoglobulinemia or cryoglobulinemic vasculitis (CV). METHODS: Fifty-nine patients with CV and related skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy were enrolled. In CV patients who also had hepatitis C virus (HCV) infection, treatment of the HCV infection with antiviral agents had previously failed or was not indicated. Patients were randomized to the non-RTX group (to receive conventional treatment, consisting of 1 of the following 3: glucocorticoids; azathioprine or cyclophosphamide; or plasmapheresis) or the RTX group (to receive 2 infusions of 1 gm each, with a lowering of the glucocorticoid dosage when possible, and with a second course of RTX at relapse). Patients in the non-RTX group who did not respond to treatment could be switched to the RTX group. Study duration was 24 months. RESULTS: Survival of treatment at 12 months (i.e., the proportion of patients who continued taking their initial therapy), the primary end point, was statistically higher in the RTX group (64.3% versus 3.5% [P < 0.0001]), as well as at 3 months (92.9% versus 13.8% [P < 0.0001]), 6 months (71.4% versus 3.5% [P < 0.0001]), and 24 months (60.7% versus 3.5% [P < 0.0001]). The Birmingham Vasculitis Activity Score decreased only after treatment with RTX (from a mean ± SD of 11.9 ± 5.4 at baseline to 7.1 ± 5.7 at month 2; P < 0.001) up to month 24 (4.4 ± 4.6; P < 0.0001). RTX appeared to be superior therapy for all 3 target organ manifestations, and it was as effective as conventional therapy. The median duration of response to RTX was 18 months. Overall, RTX treatment was well tolerated. CONCLUSION: RTX monotherapy represents a very good option for severe CV and can be maintained over the long term in most patients.

Invasive behaviour of the marine Rhodophyta Sphaerococcus coronopifolius Stackhouse, in a hypereutrophic Mediterranean lagoon.

Between 2017 and 2022, sediment labile organic matter, physico-chemical and nutrient content of the water column, biomass and C, N, P, S content of Sphaerococcus coronopifolius, a Rhodophyta that produced vegetative blooms in an area of the Orbetello lagoon (Italy) not far from the effluents of two land-based fish-farms, were examined and compared with an area even further away from that source where the species was not found. In order to understand the reasons for an important mat development in only one specific area, microcosm experiments were also carried out. Results suggest the species developed in dense and extensive mats under high orthophosphate and nitrate nitrogen ion concentrations conditions, behaving as an opportunistic species.

Preliminary classification criteria for the cryoglobulinaemic vasculitis.

BACKGROUND: To develop preliminary classification criteria for the cryoglobulinaemic syndrome or cryoglobulinaemic vasculitis (CV). METHODS: Study part I developed a questionnaire for CV to be included in the formal, second part (study part II). Positivity of serum cryoglobulins was defined by experts as an essential condition for CV classification. In study part II, a core set of classification items (questionnaire, clinical and laboratory items, as agreed) was tested in three groups of patients and controls-that is, group A (new patients with the CV), group B (controls with serum cryoglobulins but lacking CV) and group C (controls without serum cryoglobulins but with features which can be observed in CV). RESULTS: In study part I (188 cases, 284 controls), a positive response to at least two of three selected questions showed a sensitivity of 81.9% and a specificity of 83.5% for CV. This questionnaire was employed and validated in study part II, which included 272 patients in group A and 228 controls in group B. The final classification criteria for CV, by pooling data from group A and group B, required the positivity of questionnaire plus clinical, questionnaire plus laboratory, or clinical plus laboratory items, or all the three, providing a sensitivity of 88.5% and a specificity of 93.6% for CV. By comparing data in group A versus group C (425 controls), the same classification criteria showed a sensitivity 88.5% and a specificity 97.0% for CV. CONCLUSION: Classification criteria for CV were developed, and now need validation.

Duplication of a permanent maxillary incisor root caused by trauma to the predecessor primary tooth: clinical case report.

AIM: This report describes a permanent maxillary incisor tooth with two roots possibly caused by trauma to the predecessor primary tooth. SUMMARY: Diagnosis, aetiology, clinical implications and endodontic and aesthetic treatment of an incisor tooth with two roots are presented. Diagnosis, early intervention by a multidisciplinary team and clinical and radiographic examination of patients who suffer trauma to primary teeth are of importance to minimize or avoid damage to successor teeth. KEY LEARNING POINTS: • A possible sequelae of trauma to a primary tooth is root duplication in the permanent tooth. • Root duplication is a rare anomaly that has its diagnosis based on the radiographic examination. • Careful diagnosis and follow-up are necessary to prevent future complications related to the successor tooth.

Assessment of the causes of Hg bioaccumulation in the fish of a Mediterranean lagoon subject to environmental management interventions.

In a Mediterranean lagoon characterized by high levels of Hg in the sediment, Hg content in commercial fish species was determined, and, in order to establish Hg concentration in the water column, Diffusive Gradient in Thin films technique (DGT) was used. The results allowed to state (1) the disturbance of the surface sediment and its resuspension in the water column did not cause detectable increase in Hg releases, (2) the East basin acted more than the West one in contamination of fish species, (3) the small-sized sea-breams (<400 g) were more contaminated than larger sizes ones (>400 g). We concluded: (1) fish contamination may also depend on direct contact with releases of the contaminant and small, gregarious and less sedentary subjects are more likely to incur releases of Hg; (2) Hg releases can be greater in areas with a relatively low sedimentary organic matter load compared to areas subjected to high density macroalgal mat, regardless of the amount of Hg present in the sediments; (3) wind transport of plant masses in low energy storage areas, may constitute an increase factor of Hg in the sediment. A critical review of the results was made in comparison with the available literature reports and some hypotheses were proposed regarding the possible dynamics and availability of the contaminant.

Traumatic injuries in primary dentition and their immediate and long-term consequences: a 10-year retrospective study from the State University of Rio de Janeiro, Brazil.

BACKGROUND/AIM: Dental trauma is a highly prevalent problem worldwide. The aim of this study was to describe characteristics of trauma to anterior primary teeth and its sequelae for primary and successor teeth over a 10-year period of assistance at the paediatric dental traumatology clinic in the State University of Rio de Janeiro, Brazil. MATERIALS AND METHODS: The data were obtained from the dental records of children assisted from 2006 to 2016. Inclusion criteria were trauma to anterior primary teeth; aged <1 to 9 years at the time of trauma; and at least one follow-up appointment. The data concerning traumatized teeth, child's age, soft tissue injuries, types of traumatic dental injuries and sequelae in both dentitions were collected. RESULTS: Of the 1230 dental records, 483 (39.3%) were eligible, consisting of 815 teeth. The mean age at the time of trauma was 37.4 months (239 males and 244 females). The most important characteristics were: tooth 51 was most affected; falls, at home, on a ceramic floor, were the main cause; gingival laceration, enamel fracture and intrusive luxation were the most frequent types of trauma; premature tooth loss of primary teeth and enamel discoloration in their successor were the most frequent sequelae; and injuries in the periodontal tissue were demonstrated as the highest risk for sequelae in successors (OR, 3.798; p< 0.001). CONCLUSIONS: Most traumatic injuries occur in young children, in their home environment. Consequences for the primary teeth were more frequent compared to the permanent successor tooth. Traumatized primary teeth involving periodontal tissue have more chances to result in sequelae to their successor teeth.

Fokker-Planck equation in a wedge domain: anomalous diffusion and survival probability.

We obtain exact solutions and the survival probability for a Fokker-Planck equation subjected to the two-dimensional wedge domain. We consider a spatial dependence in the diffusion coefficient and the presence of external forces. The results show an anomalous spreading of the solution and, consequently, a nonusual behavior of the survival probability which can be connected to anomalous diffusion.

Extensions and solutions for nonlinear diffusion equations and random walks.

We investigate a connection between random walks and nonlinear diffusion equations within the framework proposed by Einstein to explain the Brownian motion. We show here how to properly modify that framework in order to handle different physical scenarios. We obtain solutions for nonlinear diffusion equations that emerge from the random walk approach and analyse possible connections with a generalized thermostatistics formalism. Finally, we conclude that fractal and fractional derivatives may emerge in the context of nonlinear diffusion equations, depending on the choice of distribution functions related to the spreading of systems.

Self-reported recurrent pain and medicine use among 15-year-olds: results from the HBSC Italian study.

BACKGROUND: The prevalence of adolescent pain varies considerably across epidemiological studies, and little information is available on pain-related behaviours among adolescents, including medicine use. The aims of this study were: [1] to examine the prevalence of recurrent pain among 15-year-old adolescents in Italy; [2] to investigate the association between recurrent pain and medicine use among boys and girls; and [3] to evaluate the consistency of these associations across Regions. METHODS: The World Health Organization (WHO) collaborative International Health Behaviour in School-aged Children 2013/2014 study collected self-reported data on pain and medicine use from 13611 15-year-old adolescents in 21 Italian Regions. We used multi-level multivariate logistic regression, stratified by gender, to analyse the association between recurrent pain and medicine use for headache, stomachache, nervousness and difficulties in getting to sleep. RESULTS: On average, across all Regions, almost 45% of adolescents reported recurrent headache, more than 30% reported recurrent backache and approximately 30% reported recurrent stomachache. Although the prevalence of both pain and medicine use was much higher among girls, the association between pain and medicine use was similarly strong in adolescents of both genders. Adolescents with recurrent pain proved more likely to use medicines also for non-corresponding pain, nervousness and difficulties in getting to sleep. The association between recurrent pain and medicine use was consistent across Regions despite large inter-regional differences in the prevalence of both phenomena. CONCLUSIONS: Recurrent pain in adolescence is common nationwide. Adolescents with recurrent pain are more likely to use medicines in general. Recurrent pain and medicine use should be addressed by adolescent health policies.

Interaction of the isothiocyanate sulforaphane with drug disposition and metabolism: pharmacological and toxicological implications.

Isothiocyanates (ITCs) are sulfur-containing compounds that are broadly distributed among cruciferous vegetables such as cabbages and broccoli. The consumption of ITCs is expected to rise due to the use of dietary supplements and public health initiatives promoting the consumption of more fruits and vegetables. Sulforaphane (SFN) is by far the most widely studied and characterized ITC. SFN is extensively metabolized and can therefore compete with other substrates of Phases I, II, III enzymes and transporters. In addition, it has an unusually high potency as an inducer of phase II enzymes and regulates the expression and function of different cytochrome P-450 genes. Such effects can be beneficial and may indicate a mechanism for the preventive role that SFN is believed to play against the degenerative events of aging and chronic diseases. Furthermore, these gene induction effects and the interaction with detoxification responses can modify bioavailability and in vivo bioactivity of drugs. This review will discuss 1) the metabolism of ITCs using SFN as an example, 2) inhibition of drug metabolism by SFN, and 3) induction of drug metabolizing enzymes by SFN. The potential pharmacological and toxicological implications of these effects on drug metabolism will also be discussed.

Chemoprevention of cancer by isothiocyanates and anthocyanins: mechanisms of action and structure-activity relationship.

Carcinogenesis is a multi-step, multi-path and multi-focal process, which involves a series of epigenetic and genetic alterations that begin with genomic instability and end with the development of cancer. This long and complex process presents opportunities for the development of interventions both in preventing cancer initiation and in treating the neoplasm during its premalignant stages. Failure and high systemic toxicity of conventional cancer therapies have accelerated the search for newer agents, which could prevent and/or slow-down cancer growth and have more human acceptability by being less or non-toxic. Now, it is recognized that diets rich in fruits and vegetables are associated with lower risk of cancer. Taking cue from these observations, there is a strong interest in isolating and characterizing the nutritive and non-nutritive components of fruits and vegetables as potential chemopreventive agents. Isothiocyanates and anthocyanins, present in widely consumed fruits and vegetables, are two such agents. In recent years, increasing body of evidence has underscored the cancer preventive efficacy of isothiocyanates and anthocyanins in both in vitro and in vivo animal models. In this review article, we will provide detailed insight into the chemopreventive efficacy of isothiocyanates and anthocyanins based on the evidence generated from various studies performed using cell culture or animal models of epithelial cancers. Moreover, we will discuss the potential clinical relevance of the observed chemopreventive effects of these agents.

Comprehensive molecular cytogenetic analysis of the human blastocyst stage.

BACKGROUND: The high frequency of chromosomal abnormalities observed in human gametes and embryos is unlike that seen in other mammalian species and is of great clinical significance, leading to high rates of pregnancy loss, and live-born children with aneuploid syndromes. Although much is known concerning the aneuploidy rates of oocytes, cleavage stage embryos and fetuses during pregnancy, the chromosomal status of blastocysts has been relatively little investigated. METHODS: A total of 158 good quality blastocysts were examined using micromanipulation, whole genome amplification and comparative genomic hybridization. RESULTS: From the obtained data, it was evident that the aneuploidy rate (38.8%) is significantly lower for blastocysts than for embryos at earlier stages (51%). However, in many cases, chromosome errors, including monosomy, imbalance affecting the larger chromosomes and complex aneuploidy persisted to this final stage of preimplantation development. CONCLUSIONS: This study represents the first attempt to gain a detailed insight into the extent and type of chromosome errors seen at the blastocyst stage, using a comprehensive molecular cytogenetic method. Our data suggest that the blastocyst stage does not represent an absolute selective barrier, and that the majority of aneuploid embryos are lost at the time of implantation or shortly thereafter.

Hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C, and intercellular adhesion-1 molecules. Clues to pathogenesis of hepatocellular damage and response to interferon treatment in patients with chronic hepatitis C.

To obtain information on the mechanisms of hepatocellular damage and the determinants of response to interferon, hepatitis C virus (HCV) genotype, tissue HCV antigens, hepatocellular expression of HLA-A,B,C and intercellular adhesion-1 molecules, and the number of lobular T lymphocytes were studied in 38 anti-HCV-positive patients. 14 patients did not show a primary response to interferon treatment. HCV genotype 1b was detected in 11 of them. They displayed higher scores of HCV-positive hepatocytes, HLA-A,B,C, and ICAM-1 molecules expression than with the responders. HCV-infected hepatocytes maintained the capacity to express HLA-A,B,C and ICAM-1 molecules. CD8-positive T cells in contact with infected hepatocytes and Councilman-like bodies were observed. A significant correlation was found between the number of lobular CD8-positive T cells and alanine amino transferase levels. No differences were observed in clinical, biochemical, and histological features between patients with high and low number of hepatocytes containing HCV antigens. These data suggest a prominent role of T cell-mediated cytotoxicity in the genesis of hepatocellular damage. The high expression of interferon-inducible antigens like HLA-A,B,C molecules suggests the presence of strong activation of the interferon system possibly related to high HCV replication in nonresponder patients infected with genotype 1b.

Antibodies to SS-A/Ro-52kD and centromere in autoimmune liver disease: a clue to diagnosis and prognosis of primary biliary cirrhosis.

BACKGROUND: Primary biliary cirrhosis (PBC) may be associated with various rheumatological disorders. AIM: To investigate the frequency and significance of 'rheumatological' antinuclear antibodies in the field of autoimmune chronic liver disease, with special regard to PBC. METHODS: We studied 105 patients with PBC, 162 autoimmune liver disease controls (type 1 and 2 autoimmune hepatitis, primary sclerosing cholangitis), 30 systemic lupus erythematosus and 50 blood donors. Sera were tested for the presence of antibodies to extractable nuclear antigens (anti-ENA) by counterimmunoelectrophoresis, enzyme-linked and immunoblot (IB) assay, and for the presence of anti-centromere antibodies (ACA) by indirect immunofluorescence on HEp-2 cells and IB. RESULTS: The overall prevalence of IB-detected anti-ENA in PBC (30%) was higher than in type 1 autoimmune hepatitis (2.5%, P < 0.0001), type 2 autoimmune hepatitis (0%, P < 0.0001) and primary sclerosing cholangitis (11.5%, P = 0.006) and lower than in systemic lupus erythematosus (53%, P = 0.03). The most frequent anti-ENA reactivity in PBC was anti-SSA/Ro-52kD (28%). ACA were detected by IB in 21% PBC patients and never in the other subjects (P < 0.0001). Anti-SS-A/Ro/52kD positive PBC patients had at the time of diagnosis a more advanced histological stage (P = 0.01) and higher serum levels of bilirubin (P = 0.01) and IgM (P = 0.03) compared with negative ones. CONCLUSIONS: In the autoimmune liver disease setting, anti-SS-A/Ro-52kD and ACA have a high specificity for PBC and can thus be of diagnostic relevance in anti-mitochondrial antibodies negative cases. If confirmed in further studies with adequate follow-up, anti-SS-A/Ro-52kD antibodies might identify PBC patients with a more advanced and active disease.

Fractional diffusion equation in a confined region: surface effects and exact solutions.

Surface effects on a diffusion process governed by a fractional diffusion equation in a confined region with spatial and time dependent boundary conditions are investigated. First, we consider the one-dimensional case with the boundary conditions rho(0,t)=Phi0(t) and rho(a,t)=Phia(t). Subsequently, the two-dimensional case in the cylindrical symmetry with rho(a,theta,t)=Phia(theta,t) and rho(b,theta,t)=Phib(theta,t) is investigated. For these cases, we also obtain exact solutions for an arbitrary initial condition by using the Green's function approach.

Expert clinical management of autoimmune hepatitis in the real world.

BACKGROUND: High-quality data on the management of autoimmune hepatitis (AIH) are scarce. Despite published guidelines, management of AIH is still expert based rather than evidence based. AIM: To survey expert hepatologists, asking each to describe their practices in the management of patients with AIH. METHODS: A survey questionnaire was distributed to members of the International AIH Group. The questionnaire consisted of four clinical scenarios on different presentations of AIH. RESULTS: Sixty surveys were sent, out of which 37 were returned. None reported budesonide as a first line induction agent for the acute presentation of AIH. Five (14%) participants reported using thiopurine S-methyltransferase measurements before commencement of thiopurine maintenance therapy. Thirteen (35%) routinely perform liver biopsy at 2 years of biochemical remission. If histological inflammatory activity is absent, four (11%) participants reduced azathioprine, whereas 10 (27%) attempted withdrawal altogether. Regarding the management of difficult-to-treat patients, mycophenolate mofetil is the most widely used second-line agent (n = ~450 in 28 centres), whereas tacrolimus (n = ~115 in 21 centres) and ciclosporin (n = ~112 in 18 centres) are less often reported. One centre reported considerable experience with infliximab, while rescue therapy with rituximab has been tried in seven centres. CONCLUSIONS: There is a wide variation in the management of patients with autoimmune hepatitis even among the most expert in the field. Although good quality evidence is lacking, there is considerable experience with second-line therapies. Future prospective studies should address these issues, so that we move from an expert- to an evidence- and personalised-based care in autoimmune hepatitis.

Antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns: diagnostic accuracy for primary biliary cirrhosis.

BACKGROUND: Serum antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns are frequently detected by indirect immunofluorescence on HEp-2 cells in patients with primary biliary cirrhosis. AIM: To assess the accuracy of multiple nuclear dot and rim-like/membranous antinuclear antibodies for the diagnosis of primary biliary cirrhosis. METHODS: Sera from 4371 consecutive patients referred to our laboratory were analysed under code for antinuclear antibodies testing by indirect immunofluorescence on HEp-2 cells. RESULTS: Review of the clinical records of the 4371 patients allowed identification of 101 patients with antimitochondrial antibody-positive primary biliary cirrhosis and 22 with antimitochondrial antibody-negative variant. Multiple nuclear dot and/or rim-like/membranous patterns were found in 59 (1.3%) of the 4371 patients: 31 antimitochondrial antibody-positive primary biliary cirrhosis, 17 antimitochondrial antibody-negative primary biliary cirrhosis and 11 non-primary biliary cirrhosis. The specificity for primary biliary cirrhosis of both the antinuclear antibodies pattern was 99%. Positive predictive value and likelihood ratio for a positive test were 86% (95% CI: 72.7-94) and 221 (95% CI: 91.7-544) for multiple nuclear dot, 79% (95% CI: 62.2-90.1) and 132 (95% CI: 56.8-312.7) for rim-like/membranous, respectively. CONCLUSIONS: Multiple nuclear dot and rim-like/membranous antinuclear antibodies are rare findings. Their positivity strongly suggests the diagnosis of primary biliary cirrhosis, irrespective of antimitochondrial antibody status. The high specificity for primary biliary cirrhosis makes them a useful diagnostic tool especially in antimitochondrial antibody-negative patients.

Antibodies to filamentous actin (F-actin) in type 1 autoimmune hepatitis.

AIMS: To evaluate the diagnostic significance of anti-filamentous actin antibodies (A-FAA) assessed with a commercial ELISA in comparison with immunofluorescence reactivity and patterns of anti-smooth muscle antibodies (SMA); and to correlate A-FAA positivity with clinical, immunogenetic, laboratory, and histological features in patients with autoimmune hepatitis type 1 (AIH-1). METHODS: We studied 78 consecutive untreated AIH-1 patients and 160 controls: 22 with autoimmune hepatitis type 2 (AIH-2), 51 with hepatitis C, 17 with coeliac disease (CD), 20 with primary biliary cirrhosis (PBC) and 50 blood donors. SMA was evaluated by indirect immunofluorescence (IIF) on frozen sections of rat tissues, and A-FAA with a modified commercial ELISA. RESULTS: SMA was detected by IIF in 61 (78%) of 78 AIH-1 patients, of whom 47 (60%) had the SMA-T/G and 14 (18%) the SMA-V pattern. Of the pathological controls, 32 (20%) had the SMA-V pattern (25 with hepatitis C, 2 with AIH-2, 2 with PBC, 3 with CD). A-FAA were present in 55 AIH-1 patients (70.5%; 46 with SMA-T/G, 7 with SMA-V, and 2 SMA-negative), and in 10 controls (6%), of whom five had hepatitis C, two AIH-2, two PBC and one CD. The association between A-FAA and the SMA-T/G pattern was statistically significant (p<0.0001). A-FAA levels were higher in SMA-T/G positive than SMA-V positive AIH-1 patients and controls (p<0.0001). A-FAA positivity was significantly associated with higher gamma-globulin and IgG levels, but did not correlate with other considered parameters. CONCLUSION: The modified A-FAA ELISA strictly correlates with the SMA-T/G pattern and is a reliable and operator independent assay for AIH-1. Detection of A-FAA, even if devoid of prognostic relevance, may be useful when interpretative doubts of standard IIF arise.