bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Implications of Numb Immunoreactivity in Salivary Gland Carcinomas
Authors: Maiorano E. , Favia G. , Pece S. , Resta L. , Maisonneuve P. , Di Fiore P.P. , Capodiferro S. , Urbani U. , Viale G.
Published: January 2017

The gene numb encodes for a protein (Numb) involved in cell fate decisions in Drosophila, with proposed endocytic and developmental functions in mammalians. The distribution pattern of Numb in human tissues however, has not been fully characterized. We set out to explore the immunohistochemical expression of Numb in normal and neoplastic (28 adenoid cystic and 34 mucoepidermoid carcinomas) salivary glands, and correlated the results with the clinico-pathologic features of the neoplasms. Intense Numb immunoreactivity was detected in normal ductal cells and in a subset of acinar cells. In salivary carcinomas, we detected diffuse and intense Numb immunostaining in 5 adenoid cystic and 8 mucoepidermoid carcinomas. By contrast, the majority of adenoid cystic and mucoepidermoid cancers showed only moderate (14 and 5 cases) or focal staining (9 and 21 cases), respectively. The corresponding expression of Numb mRNA was documented in normal parotid gland and adenoid cystic carcinoma. Numb immunoreactivity was inversely correlated with the histological grade and Ki-67 immunoreactivity of both adenoid cystic and mucoepidermoid carcinomas. In addition, while tumor grade, stage, Ki-67 and Numb immunoreactivity were associated with disease-free survival in univariate analysis, only Numb and Ki-67 immunoreactivities retained independent prognostic significance in multivariate analysis. These data suggest that loss of Numb is implicated in aberrant differentiation programs of salivary gland carcinomas and may serve as a prognostic indicator in patients treated for these neoplasms.
Extragenital Lichen Sclerosus and Atrophicus Treated with Topical Steroids and Retinoids in a Child with Vitiligo
Authors: Guerriero C. , Manco S. , Paradisi A. , Capizzi R. , Fossati B. , Fabrizi G.
Published: January 2017

Lichen sclerosus and atrophicus (LSA) most commonly affects the anogenital region. Extragenital involvement is rare, and women are reported to be affected 6 to 10 times more often than men. The aetiology of LSA is unclear, but genetic, physiological and environmental factors are thought to be involved. Several lines of evidence support the hypothesis of an autoimmune basis for LSA; an increased incidence of tissue-specific antibodies and an association with autoimmune disorders such as vitiligo, alopecia areata, thyroid disease and pernicious anaemia have been reported. We describe a paediatric patient with extragenital LSA associated with vitiligo who was successfully treated with topical steroids and retinoids.
Andolast Acts at Different Cellular Levels to Inhibit Immunoglobulin E Synthesis
Authors: Malerba M. , Mennuni L. , Piepoli T. , Caselli G. , Makovec E , Rovati L.C. , D'Amato M. , Ferrari F.
Published: January 2017

The anti-asthmatic agent andolast is thought to inhibit the release of allergic mediators, but its mechanism of action is not fully understood. We investigated whether the compound inhibits immunoglobulin E (IgE) synthesis and tested the hypothesis that andolast affects immunoglobulin class switching. Interleukin (IL)-4 and the interaction of CD40 expressed on B cells with its ligand on T cells are necessary for IgE synthesis. Thus, peripheral blood mononuclear cells (PBMCs) from 40 asthmatic, 16 non-asthmatic allergic, and 9 normal donors were stimulated with IL-4 and/or anti-CD40 antibody. T cells from 9 additional allergic donors were activated with anti-CD3/CD28 antibodies to express IL-4 mRNA. After incubation in the absence or presence of test compounds, immunoglobulin concentrations were measured by enzyme immunoassay, and mRNA levels were analyzed by RT-PCR. Andolast significantly inhibited IgE synthesis by stimulated PBMCs from both asthma patients and combined allergic/normal donors. In mechanistic studies, andolast was found to act at different cellular levels. Firstly, it reduced by about 45% (p<0.05) the levels of IL-4 mRNA in T cells stimulated with anti-CD3/CD28. Secondly, andolast reduced by about 36% (p<0.05) the expression of epsilon (ε) germline transcripts in PBMCs stimulated with IL-4/anti-CD40. Thirdly, the effect of andolast on immunoglobulin synthesis was selective in that the production of IgG4 antibodies was not significantly inhibited. Our findings, while supporting the evidence that andolast is effective for the treatment of asthma, provide new insights into its mechanism of action.
Exploiting Immunotherapy in Mycobacterium Tuberculosis-Infected MICE: Sphingosine 1-Phosphate Treatment Results in a Protective or Detrimental Effect Depending on the Stage of Infection
Authors: Sali M. , Delogu G. , Greco E. , Rocca S. , Colizzi V. , Fadda G. , Fraziano M.
Published: January 2017

Sphingosine 1-phosphate (S1P) is a natural lysophospholipid able to enhance antimycobacterial innate immune response. In the present study, we address the possible therapeutic role of S1P administered during primary or acute infection in mice aerogenically infected with Mycobacterium tuberculosis (MTB). Results show that the administration of S1P during primary infection significantly reduces the presence of MTB-infected cells within pulmonary granulomas and mycobacterial burden in the lung and in the spleen. However, if S1P treatment was started during acute infection, a detrimental effect was observed in terms of pulmonary histopathology and mycobacterial burden in the lung and in the spleen. Taken together, these results show that S1P can exert a therapeutic effect as a treatment of primary infection only.
High-Dose Inhaled Flunisolide versus Budesonide in the Treatment of Acute Asthma Exacerbations in Preschool-Age Children
Authors: Decimo F. , Maiello N. , Del Giudice M. Miraglia , Amelio R. , Capristo C. , Capristo A.F.
Published: January 2017

The role of inhaled corticosteroids in asthma exacerbation is debated. We compared high doses of nebulized budesonide versus high doses of nebulized flunisolide, in association with a short-acting beta-2-agonist, in the treatment of moderate asthma exacerbation in preschool children. In this randomized, parallel group, simple blind study, 46 children aged between 3 and 5 years affected by an acute moderate asthma attack were treated with nebulized flunisolide (Group 1) 40 μg/kg twice daily for 7 days and then 20 μg/kg twice daily for 14 days, or with nebulized budesonide (Group 2) 0.5 mg twice daily for 7 days then 0.25 mg twice daily for 15 days. Inhaled salbutamol (MDI+ spacer − 200 μg 4 times daily) was administered during the first 3 days of the study and then as needed. At TO, T7 and T21 days, airway resistances were evaluated with the forced oscillation technique before and after inhalation of inhaled salbutamol (200 mcg). Parents recorded symptoms and drug use on a diary card. Forty children completed the study. Airway resistances were significantly reduced at T7 (p< 0.01 flunisolide; p< 0.05 budesonide) and T21 (p< 0.05 flunisolide; p< 0.05 budesonide) versus T0 in both groups, although at T7 the reduction occurred faster in group 1 than in group 2 (p<0.01). During the first 7 days of treatment, symptom scores decreased in both groups; however, the decrease was greater in group 1 (p< 0.05). High doses of inhaled flunisolide and budesonide are both effective in the management of moderate asthma exacerbations in pre-school-age children, but the flunisolide therapeutic effect was faster than budesonide.
Ultrasound-Guided Hyaluronic Acid Injection in Carpometacarpal Osteoarthritis: Short-Term Results
Authors: Salini V. , De Amicis D. , Abate M. , Natale MA. , Di Iorio A.
Published: January 2017

Carpometacarpal osteoarthritis (CMC-OA) is a disabling condition, characterized by pain and functional impairment. The aim of the present study is to evaluate the efficacy of a single ultrasound-guided injection of hyaluronic acid (HA) in patients suffering from CMC-OA. Eighteen patients with CMC-OA, grade 2–3 Kellgren and Lawrence score, attending the Orthopaedic Department of the University Hospital of Chieti, were enrolled. They underwent clinical evaluation at baseline and after one month follow-up, evaluating: grading of pain (VAS at rest and during activities), function (Dreiser Index), grip and pinch strengths (Jamar dynamometer), as well as NSAIDs consumption. Each patient received a single ultrasound- guided injection of HA into the articular CMC joint. The results were that pain at rest and during activities decreased from 1.8 ± 1.07 to 0.5 ± 0.68 (p < 0.001) and from 8.05 ± 0.94 to 4.15 ± 1.42 (p < 0.001), respectively. Dreiser Functional Index showed a significant improvement (+11.59 %; p < 0.004), as well as pulp pinch strength (24.07 %; p < 0.001). The consumption of NSAIDs was also clearly reduced, from 16 to 7 patients (-45%) and from 2.45 ± 1.98 to 1.15 ± 1.30 tablets per week (p < 0.02). Mild local side effects, lasting less than 3 hours, were observed only in 2 cases. A single ultrasound guided injection of HA is a safe and effective procedure in CMC-OA, with a significant improvement in terms of pain and function. However, studies with larger samples and longer term follow-up are warranted.
Successful Treatment with Etanercept of a Patient with Psoriatic Arthritis after Adalimumab-Related Hepatotoxicity
Authors: Massarotti M. , Marasini B.
Published: January 2017

Inhibitors of Tumor Necrosis Factor (TNF) alpha (infliximab, etanercept, adalimumab) are nowadays widely used for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), not responding to conventional therapies. Anti-TNF alpha drugs have demonstrated great efficacy in slowing the disease, however, to date, concern still remains regarding acute and long-term toxicity related to TNF block. Increase in liver tests may be observed during treatment with anti-TNF agents, more often related to concomitant drugs (i.e. NSAIDS, methotrexate) or to reactivation of chronic HBV or HCV infections. However, liver damage directly induced by the drug has been described in patients treated with infliximab or adalimumab. To our knowledge, no cases of liver injury closely related to etanercept have been reported so far. We report the case of a patient with PsA who presented liver dysfunction during adalimumab, subsequently successfully treated with etanercept.
Molecular Study of Receptor for Advanced Glycation Endproduct Gene Promoter and Identification of Specific HLA Haplotypes Possibly Involved in Chronic Fatigue Syndrome
Authors: Carlo-Stella N. , Bozzini S. , De Silvestri A. , Sbarsi I. , Pizzochero C. , Lorusso L. , Martinetti M. , Cuccia M.
Published: January 2017

The receptor for advanced glycation end product (RAGE) is thought to play an important role in inflammation. Chronic Fatigue Syndrome (CFS) is a long-lasting fatigue that compromises at least 50% of a subject's daily activities without other known cause. Immune dysfunction has been implicated and an association with a peculiar genetic cytokine profile, predisposing to an immunomodulatory response of inflammatory nature, was found. The aim of this study is to analyse RAGE polymorphisms and HLA-DRB1 alleles in seventy-five Italian CFS patients and 141 controls matched for age, sex and ethnicity. These two groups underwent genomic study for RAGE –374T/A and –429C/T promoter polymorphisms; moreover, 46 patients and 186 controls were typed for HLA-DRB1 at low resolution molecular level. Of these, 31 patients and 99 controls also underwent “high resolution analysis” to define the HLA-DRB1*11 and DRB1*13 alleles. The haplotypes RAGE-374T, DRB1*04; RAGE-374T, DRB1*09; RAGE-374T, DRB1*11; RAGE-374A, DRB1*13; RAGE-429T, DRB1*04 and RAGE-429C, DRB1*11 were significantly more frequent in CFS patients, whereas RAGE-429C, DRB1*07 would seem protective. A significantly lower frequency of DRB1*1104 (5.4% vs 12.9% p=0.04, OR=0.39) and a significantly higher frequency of HLA-DRB1*1301 (13.0% vs 5.1% p=0.006, OR= 2.79) were found in CFS patients. A synergic effect was observed with RAGE polymorphism. The OR values strengthened in the following cis combinations: RAGE-374A, HLA-DRB1*1104 (OR=0.27) and RAGE-374A, HLA-DRB1*1301 (OR=6.23). HLA haplotypes rather than single alleles of RAGE or of DRB1 genes seem to be involved in CFS, probably including a subregion of major interest.
Evidence of an Involvement of TFAP2A Gene in Nonsyndromic Cleft LIP with or without Cleft Palate: An Italian Study
Authors: Martinelli M. , Masiero E. , Carinci F. , Morselli P.G. , Palmieri A. , Girardi A. , Baciliero U. , Scapoli L.
Published: January 2017

Unraveling of factors involved in multifactorial diseases is a great challenge. Different approaches can be contemplate and applied to a variety of congenital malformations. In the present investigation TFAP2A has been considered a good candidate gene for nonsyndromic cleft lip with or without cleft palate (NSCLP) aetiology, basing on a sum of considerations. TFAP2A has been seen involved in orofacial development in mice; it is located in the NSCLP candidate region 6p24; it codes for a transcription factor which regulates expression of IRF6, a gene implied in NSCLP; finally, it is embroiled in the branchiooculofacial syndrome, that includes clefting as feature. A family based association analysis was performed with a sample study of 405 NSCLP triads. Evidence of association was obtained with both single marker and haplotype analyses, thus providing a support for TFAP2A in NSCLP aetiology.
A Comparison of Antibiotic Release between a Cement Scaffold, a Perforated Cement Scaffold and a Cement Scaffold Mixed to Calcium Sulphate: In vitro Study
Authors: Zoccali C. , Contestabile M. , Di Segni S. , Nuvoli B. , Prencipe U. , Erba F.
Published: January 2017

One of the most dangerous possible complications in joint replacement is infection due to bacteria adhere to prosthesis surface making biofilm difficult to erase. The gold standard treatment consists in prosthesis removal, placement of antibiotic-impregnated cement spacer and systemic antibiotics therapy. When the infection heals a new prosthesis is implanted. The antibiotic-impregnated spacer is important to maintain the prosthesis space and to guarantee a local high concentration of antibiotics. The release of the antibiotic by the cement happens at its surface so that, increasing this, the concentration of antibiotic should be increased as well. The aim of the present study is to verify the different release of antibiotic in plasma by different groups of scaffolds to identify the best solution to make the antibiotic spacer in septic prosthesis revision. Six groups of three antibiotic impregnated cement cube-shaped have been done. The first, made by only antibiotic and cement, the second by a double concentration of the antibiotic and cement, the third made by the antibiotic cement and perforated in every surface with a needle before hardening, the fourth similar to the previous but with a double concentration of antibiotic, the fifth by antibiotic-impregnated cement mixed with calcium sulphate pellets, the sixth similar to the previous with a double concentration of antibiotic. The cubes were immersed in plasma and the concentration of antibiotic released valued at specific times. The perforated cement scaffold demonstrated the best result during the first four weeks.
Side Effects of Radiation in Musculoskeletal Oncology: Clinical Evaluation of Radiation-Induced Fractures
Authors: Mavrogenis Andreas F. , Pala Elisa , Romantini Matteo , Guerra Giovanni , Romagnoli Carlo , Maccauro Giulio , Ruggieri Pietro
Published: January 2017

Radiation therapy and chemotherapy, while they remain an essential part of the multidisciplinary treatment of cancers, they have led to unwanted complications. Radiation-induced complications include wound and bone, growth, nervous system, tumorigenic, lung, gastrointestinal, hepatic and other complications. In this article we review the side effects of radiation therapy in musculoskeletal oncology emphasizing on bone, present our long experience, and discuss the current literature regarding radiation-induced bone complications and their management and outcome.
Electromagnetic Stimulation to Optimize the Bone Regeneration Capacity of Gelatin-Based Cryogels
Authors: Fassina L. , Saino E. , Visai L. , Schelfhout J. , Dierick M. , Van Hoorebeke L. , Dubruel P. , Benazzo F. , Magenes G. , Van Vlierberghe S.
Published: January 2017

One of the key challenges in reconstructive bone surgery is to provide living constructs that possess the ability to integrate in the surrounding host tissue. Bone graft substitutes and biomaterials have already been widely used to heal critical-size bone defects due to trauma, tumor resection and tissue degeneration. In the present study, gelatin-based cryogels have been seeded with human SAOS-2 osteoblasts followed by the in vitro culture of the cells. In order to overcome the drawbacks associated with static culture systems, including limited diffusion and inhomogeneous cell-matrix distribution, the present work describes the application of a bioreactor to physically enhance the cell culture in vitro using an electromagnetic stimulus. The results indicate that the physical stimulation of cell-seeded gelatin-based cryogels upregulates the bone matrix production. We anticipate that the scaffolds developed consisting of human bone proteins and cells could be applied for clinical purposes related to bone repair.
Transient Global Amnesia as the First Symptom of Primary Antiphospholipid Syndrome: A Case Report
Authors: Zardi E.M. , Zardi D.M. , Lazarevic Z. , Santucci S. , D'Errico F. , Carbone A. , Gonnella C. , Afeltra A. , Tonioni S.
Published: January 2017

We describe the case of a 45-year-old woman who had drawn our attention for some recent episodes of transient global amnesia that, upon further examination, resulted from ischemic events caused by multiple arterial thrombosis (bilateral internal carotid occlusion, significant stenosis of the right external carotid, mild stenosis of the right vertebral artery, right anterior cerebral artery occlusion and severe stenosis of the anterior descending coronary artery) due to primary antiphospholipid syndrome. Revascularisation of either carotid was not attempted. A percutaneous intervention in the anterior descending coronary artery stenosis was performed successfully. Due to severe arterial thrombosis, the patient was discharged with only duplex antiplatelet treatment and subcutaneous anticoagulant therapy, since immunotherapy is not indicated in primary APS. The occurrence of transient global amnesia should raise the suspicion of APS.
High Serum Levels of CXC (CXCL10) and CC (CCL2) Chemokines in Untreated Essential Hypertension
Authors: Antonelli A. , Fallahi P. , Ferrari S.M. , Ghiadoni L. , Virdis A. , Mancusi C. , Centannp M. , Taddei S. , Ferrannini E.
Published: January 2017

Hypertension has been suggested to exert pro-inflammatory actions through increased expression of several mediators, including chemokines. Chemokines are involved in inflammatory and autoimmune disorders, and in the formation of atherosclerotic lesions through promotion of inflammatory cell migration. The aim of this study is to evaluate the influence of high blood pressure on circulating levels of the prototype chemokines C-X-C motif ligand (CXCL)10 and C-C motif ligand (CCL)2 in 140 patients with essential hypertension not affected by thyroid disorders or overt autoimmune or inflammatory diseases, and 140 gender- and age-matched healthy controls. Mean CXCL10 and CCL2 levels were significantly higher in hypertensive patients than in controls. Among hypertensive patients, chemokines levels were higher in those with systo-diastolic hypertension compared to those with isolated systolic hypertension. In a multiple linear regression model using CXCL10 or CCL2 as dependent variables and age, body mass index, glycemia, serum creatinine, high-density-lipoprotein (HDL) and low-density-lipoprotein (LDL) cholesterol, triglycerides, and systolic or diastolic blood pressure values as covariates, only systolic or diastolic blood pressure values were significantly related to CXCL10 or CCL2 levels. In conclusion, this study demonstrates increased circulating levels of the prototype chemokines CXCL10 and CCL2 in patients with hypertension.
Oral FTY720 Administration Induces Immune Tolerance and Inhibits Early Development of Atherosclerosis in Apolipoprotein E-Deficient Mice
Authors: Huang K. , Li S.Q. , Wang W.J. , Liu L.S. , Jiang Y.G. , Feng P.N. , Wang Y.Q. , Wang S.M.
Published: January 2017

Orally administered immunomodulatory drugs have recently demonstrated the ability to induce an oral tolerance via inhibition of effector T cells and induction of certain subsets of regulatory T cells (Tregs) which have the potential to prevent several autoimmune diseases. In the present study, we hypothesized that short-term, low-dose, oral FTY720 administration may induce latency-associated peptide (LAP) Tregs and CD4+ Foxp3+ Tregs in atherogenesis, potentially resulting in remission of early development of atherosclerosis in apolipoprotein E-deficient (APOE−/-) mice. FTY720 was orally administered to APOE−/- mice 4 weeks of age on a high-cholesterol diet and atherosclerosis was assessed at 8 weeks of age. Oral administration of FTY720 significantly reduced atherosclerotic lesion formation compared with control mice. We observed a significant increase in LAP+and Foxp3+cells in the CD4+T-cell population of FTY720-treated mice in association with increased production of the anti-inflammatory cytokine transforming growth factor-β (TGF-β) as well as suppressed T-helper type 1 immune responses. Our findings reveal that short-term, low-dose oral FTY720 treatment had great benefits in inhibiting early development of atherosclerosis in mice via induction of a regulatory T-cell response and inhibition of effector T responses. These findings suggest that oral immune modulation may represent an attractive therapeutic approach to atherosclerosis.
Treatment Effects in Prostate Cancer following Traditional and Emerging Therapies
Authors: Mazzucchelli R. , Scarpelli M. , Lopez-Beltran A. , Cheng L. , Di Primio R. , Montironi R.
Published: January 2017

Treatment options for prostate cancer consist of radical prostatectomy, hormonal therapy and radiation therapy. Hormonal and radiation therapy have well-known, often profound, effects on the histological appearance of benign and malignant prostate tissue. Novel therapies including focal ablative treatments, chemotherapies and targeted molecular therapies are beginning to emerge and pathologists will play a central role in documenting the effects of these treatments at the tissue level. As such, knowledge of treatment-related changes and access to clinical information are essential to ensure accurate interpretation and reporting of post-treatment prostate specimens by pathologists.
Comparison of Antibody-Conjugated Magnetic Immunoassay and Liquid Chromatography-Tandem Mass Spectrometry for the Measurement of Cyclosporine and Tacrolimus in Whole Blood
Authors: Cangemi G. , Barco S. , Bonifazio P. , Maffia A. , Agazzi A. , Melioli G.
Published: January 2017

The aim of this work is to compare the results of a commercially available liquid chromatography tandem mass spectrometry (LC-MS/MS) method in a clinical pathology laboratory for routine Therapeutic Drug Monitoring (TDM) of cyclosporine (CsA) and tacrolimus (Tacr) in pediatric patients with those obtained with the current antibody-conjugated magnetic immunoassay (ACMIA). Whole blood levels of CsA (n= 135) and Tacr (n=100) were sequentially analyzed by using ACMIA and LC-MS/MS on pediatric transplanted patients. The differences were analyzed by using the Passing Bablok regression analysis and the Bland and Altman test. The LC-MS/MS method showed excellent reproducibility and lower limits of quantification compared to the ACMIA. A linear relationship between ACMIA and LC-MS/MS was obtained for both CsA (r= 0.9449; P<0.0001, 95% CI 0.9234 to 0.9605) and Tacr (r=0.9275; P<0.0001, 95% CI 0.8941 to 0.9506). No significant inter-method biases were observed. The analytical performances of the LC-MS/MS method make it suitable for the accurate measurement of CsA and Tacr in pediatric transplanted patients. However ACMIA results are also accurate and reliable. For this reason the choice of the method to be used in a routine clinical pathology laboratory can be made on the bases of non-analytical considerations such as costs, organization, availability of skilled personnel.
Behaviour of Perioperative Values of Haemoglobin, Haematocrit and Red Blood Cells in Elderly Patients Undergoing Lower Limb Arthroplasty: A Retrospective Cohort Study on Non-Transfused Patients
Authors: Drago L. , De Vecchi E. , Romanò C.L. , Vassena C. , Banfi G.
Published: January 2017

Little is known on how elderly patients recover pre-operative haemoglobin, haematocrit and red blood cell levels after total hip and knee arthroplasties. In this study we aimed to evaluate blood loss and recovery blood levels in relation to gender, type of surgery and preoperative haemoglobin values. We conducted a retrospective cohort study on 187 patients over 65 years of age who underwent total knee or total hip arthroplasty between January 2008 and December 2009. Preoperative blood analysis was carried out within 40 days prior to intervention followed by a 15-day postoperative follow-up. Haemoglobin recovery values in anaemic patients versus healthy patients was also estimated. All tested values decreased significantly during the first 3–5 postoperative days. Haemoglobin levels decreased statistically significantly more in males than in females, while no significant differences were observed for haematocrit and erythrocytes. Recovery of haemoglobin values did not differ significantly between healthy patients and patients with preoperative haemoglobin below 120 g/L. Furthermore, our data showed a higher blood loss in total hip arthroplasty, whilst recovery rates showed to be higher after a total knee arthroplasty procedure. In conclusion, the type of intervention and gender played an important role in blood loss and recovery rates in total joint arthroplasty.
Bcgitis and Vaccine-Derived Poliovirus Infection in a Patient with a Novel Deletion in RAG1 Binding Site
Authors: Canessa C. , Romano F. , Lippi F. , Bianchi L. , Kashef S. , Rezaei N. , Moriondo M. , Nieddu F. , Martini M. , Azzari C.
Published: January 2017

A girl who developed severe BCGitis and vaccine-derived poliovirus infection was discovered to have a novel deletion of RAG1. A neonatal screening program for SCID would identify affected infants at birth, before live vaccines are administered.
Antibacterial Efficacy and Drug-Induced Tooth Discolouration of Antibiotic Combinations for Endodontic Regenerative Procedures
Authors: Mandras N. , Roana J. , Allizond V. , Pasqualini D. , Crosasso P. , Burlando M. , Banche G. , Denisova T. , Berutti E. , Cuffini A.M.
Published: January 2017

Elimination of microbial contamination from the root canal system is a precondition for successful root canal treatment. Teeth with immature root development, necrotic pulps and apical periodontitis present multiple challenges for successful treatment. Disinfection is achieved by irrigation followed by the placement of an intracanal medicament. A mixture of ciprofloxacin, metronidazole and minocycline (3-MIX S) has been shown to be very effective in eliminating endodontic pathogens in vitro and in vivo. Among the components of the mixture, minocycline can induce tooth discolouration after long-term oral use. Therefore, the elimination of minocycline from the above-mentioned combination has been suggested to prevent the occasion of this undesirable effect. The aim of this study was to investigate the potential antimicrobial efficacy of alternative antibiotic combinations [3-MIX C (clarithromycin); 3-MIX F (fosfomycin)] against bacteria from infected root canals. An additional objective was to evaluate their discolouration potential as possible alternatives to minocycline-based intracanal medicaments. Our in vitro results clearly demonstrated that 3-MIX C and 3-MIX F had a greater antimicrobial activity than 3-MIX S, underlying that clarithromycin still had a higher capacity to kill endodontic pathogens in vitro compared to fosfomycin. Both 3-MIX C and 3-MIX F were able to avoid the permanent staining effect of the crown.
Combined Clinical, Capillaroscopic and Ultrasound Evaluation during Treatment of Plaque Psoriasis with Oral Cyclosporine
Authors: Musumeci M.L. , Lacarrubba F. , Fusto C.M. , Micali G.
Published: January 2017

Imaging techniques have only recently been utilized in combination with clinical observation to objectively quantify psoriasis severity and evaluate therapeutic response. This study evaluated the sensitivity of videodermatoscopy (VD) and ultrasound (US) imaging to assess the therapeutic effect of cyclosporine (Cs) in patients with moderate-to-severe psoriasis. Twenty patients with moderate-to-severe psoriasis were divided into two groups (A and B) based on PASI score. Group A (PASI >16) was treated with 5 mg/Kg/day Cs for 4 weeks and another 4 weeks with 3 mg/Kg/day Cs. Group B (PASI 1016) received 3 mg/Kg/day Cs for 8 weeks. A “target” plaque was selected for each subject and evaluated using a Target Lesion Score (TLS) for erythema, scaling and degree of infiltration, in addition to VD and US at baseline, 2, 4 and 8 weeks. At the end of the study, improvement rate was quicker in group A vs group B after 8 weeks of Cs therapy. All three parameters (TLS, VD and US) strongly correlated with one another. Skin thickness was the first parameter that improved, followed by TLS. In contrast, improvement in VD was delayed. Normalization rate of vascular pattern (assessed by VD) was low in both groups but higher in group A vs group B (46% vs 22%), despite virtually complete normalization by clinical and US assessment. In conclusion, while both TLS and US can be utilized in the evaluation of therapeutic efficacy in patients with plaque psoriasis, VD can provide information on vascular response to treatment, which may likely affect the duration of therapy and the relapse rates.
Formulation and Characterization of Silk Fibroin Films as a Scaffold for Adipose-Derived Stem Cells in Skin Tissue Engineering
Authors: Chlapanidas T. , Tosca M.C. , Faragò S. , Perteghella S. , Galuzzi M. , Lucconi G. , Antonioli B. , Ciancio F. , Rapisarda V. , Vigo D. , Marazzi M. , Faustini M. , Torre M.L.
Published: January 2017

Skin substitutes are epidermal, dermal or complete bilayered constructs, composed by natural or synthetic scaffolds and by adherent cells such as fibroblasts, keratinocytes or mesenchymal stem cells. Silk fibroin is a promising polymer to realize scaffolds, since it is biocompatible, biodegradable, and exhibits excellent mechanical properties in terms of tensile strength. Moreover, fibroin can be added of others components in order to modify the biomaterial properties for the purpose. The aim of this work is to prepare silk fibroin films for adipose-derived stem cell (ADSCs) culture as a novel feeder layer for skin tissue engineering. Pectin has been added to promote the protein conformational transition and construct strength, while glycerol as plasticizer, providing biomaterial flexibility. Eighteen formulations were prepared by casting method using fibroin, pectin (range 1–10% w/w), and glycerol (range 0–20% w/w); films were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry assay, to select the optimal composition. A stable fibroin conformation was obtained using 6% w/w pectin, and the best mechanical properties were obtained using 12% w/w glycerol. Films were sterilized, and human ADSCs were seeded and cultured for 15 days. Cells adhere to the support assuming a fibroblastic-like shape and reaching confluence. The ultrastructural analysis evidences typical active-cell features and adhesion structures that promote cell anchorage to the film, thus developing a multilayered cell structure. This construct could be advantageously employed in cutaneous wound healing or where the use of ADSCs scaffold is indicated either in human or veterinary field.
Treatment with a Combination of Omalizumab and Specific Immunotherapy for Severe Anaphylaxis after a Wasp Sting
Authors: Pałgan K. , Bartuzi Z. , Gotz-Żbikowska M.
Published: January 2017

Hymenoptera venom anaphylaxis after bee or wasp sting is a common problem that affects about 1.2% to 3.5% of the general population. Venom-specific immunotherapy (VIT) is an established mode of treatment for immunoglobulin (Ig) E-mediated Hymenoptera venom allergy. However, VIT may often be associated with immediate anaphylaxis which can lead to treatment withdrawal. Several cases published in recent years suggest that omalizumab, used as add-on therapy may be able to prevent anaphylaxis during VIT. We report the case of a 30-year-old woman, suffering from mild persistent asthma, who had a history of severe anaphylactic reactions after yellow jacket sting, and after eating peanuts, contact with guinea pig hair, and i.v. administration of dexamethasone natrium phosphate. Initial specific immunotherapy had to be stopped due to severe anaphylaxis (hypotension, dyspnea, and angioedema). The immunotherapy was reintroduced accompanied by the anti-immunoglobulin (Ig) E monoclonal antibody omalizumab. Subcutaneous omalizumab 150 mg was initiated 4 weeks after the anaphylaxis incident and 1 day before the resumption of VIT. Rush treatment was uneventful, and the usual cumulative dose of 111.1 μg was successfully reached. The combination of omalizumab and VIT is a valid option of therapy for these patients and could reduce asthma and food allergy symptoms.
Enhancing Effect of Electromagnetic Exposure on Calciumionophore (A23187), but Not IL-1, Induced Txa2 Release by Human Neutrophils
Authors: Reale Marcella , Panara Maria R. , Bongrazio M. , Barbacane R.C. , Conti P. , Franceschi C. , Caruso I. , Bersani F. , Gigante G.E.
Published: January 2017

The exposure of human polymorphonuclears to an extremely low frequency (3 Hz) electromagnetic field for 1 hour had an enhancing effect on thromboxane A2 release stimulated by A23187 calcium ionophore. On the contrary, IL-1 stimulation of TxA2 production was not affected by an electromagnetic field, suggesting that interleukin-1 influence on thromboxane synthesis is not due to a calcium ionophore-like action.
Thymic Hormones and Cytokines
Authors: Mastino A. , Favalli C. , Grelli S. , Garaci E.
Published: January 2017

The discovery and the first studies on thymic hormones (TH) are historically linked with their role on the developmental events of T lymphocytes that occur within the thymus. However, paradoxically, during the most recent years, much more information about the effects of TH on mature effector cells, in relation with those indicating their real functions during the T-cell differentation, have been, in fact, available.

Here we report an update discussion concerning the possible role of the cooperation between TH and cytokines in T-cell development. Moreover we illustrate the results obtained by us and other authors, demonstrating a strict connection between the action of thymosins, a family of peptides first isolated and purified from calf thymus (1), and that of cytokines.
The Potential Role of Cytokines in the Pathogenesis of Systemic Sclerosis (Scleroderma)
Authors: Gabrielli A. , Danieli M.G. , Candela M. , Ricciatti A.M. , Nitti C. , Danieli G.
Published: January 2017

Systemic sclerosis (scleroderma) is characterized by excessive fibroblastic activity taking place through mechanisms largely unknown. It has been speculated that soluble factors, collectively categorized as lymphokines or monokines, and released by inflammatory or other differentiated cells, may modulate fibroblast multiple functions including migration, chemotaxis and protein synthesis. Vascular endothelium itself, which is deeply injured in systemic sclerosis, is acting as a target for the action of cytokines and is an important producer of polypeptide mediators that contribute to the inflammatory reaction and to the establishment of fibrosis. Thus, interactions through soluble mediators between fibroblasts, endothelial cells and immunocompetent cells appear crucial for the development of systemic sclerosis lesions. The aim of the present study is to evaluate the available information on the role of cytokines and to discuss their potential influence in the pathogenesis of systemic sclerosis.
Behavioural-Genetic Perspectives on Personality Function
Authors: Jang Kerry L , Vernon Philip A , Livesley W John
Published: January 2017

In the wake of the recent announcements that the human genome has been mapped, efforts to identify the genetic loci underlying personality function will grow and intensify. Much research has already been done in this area, but it has for the most part been limited to classical biometrical approaches designed to determine if personality has a heritable basis. These so-called “heritability” studies estimate how much of the individual differences in personality are attributable to genetic differences among people. Molecular-genetic approaches, on the other hand, are designed to identify specific putative loci, but have yielded mixed results. The inconsistency in research findings can be attributed in part to the lack of sufficient numbers of genetic markers in the chromosomal regions of interest—a problem that the creation of a map of the human genome will help to rectify. This map and its inevitable refinements, however, can only advance the search for the genes for personality to a limited degree. Serious unresolved problems in the conceptualization and definition of personality and its dysfunction remain, which will hamper the search for personality genes.
Involuntary Outpatient Commitment, Community Treatment Orders, and Assisted Outpatient Treatment: What's in the Data?
Authors: Swartz Marvin S , Swanson Jeffrey W
Published: January 2017

Objective:

Involuntary outpatient commitment (OPC), also referred to as community treatment orders or assisted outpatient treatment, is a legal intervention intended to improve treatment adherence among persons with serious mental illness. This paper reviews the empirical literature on the procedure's effectiveness.

Methods:

We identified and reviewed all English-language studies of OPC and related procedures available in Medline and other bibliographic search services.

Results:

Existing naturalistic and quasi-experimental studies, taken as a whole, moderately support the view that the procedure is effective, although all do have methodological limitations. Two randomized controlled studies of OPC have conflicting findings and are reviewed in detail.

Conclusions:

On balance, empirical studies support the view that OPC is effective under certain conditions, although some of the evidence has been contested and the policy remains controversial.
Evaluation of a Children's Temper-Taming Program
Authors: Williams Susan , Waymouth Marjorie , Lipman Ellen , Mills Brenda , Evans Peter
Published: January 2017

Objective:

To examine the effectiveness of a group cognitive-behavioural therapy program in reducing anger and aggressive behaviour in children.

Method:

Study participants were 68 children aged 7 to 13 years and their parents. A total of 12 groups were run at an outpatient children's mental health centre. The children were referred to the groups by their clinician for assistance in reducing their aggressive behaviour. We obtained quantitative information on the effectiveness of the group from the children and their parents, who completed questionnaires before the first session and after the last session. The children completed the Children's Inventory of Anger (CIA), and the parents completed the Children's Hostility Inventory (CHI). We used t tests and analyses of covariance to test for posttreatment differences.

Results:

Results were available for 56 children. At posttreatment, children reported that the intensity of their anger had decreased (CIA, t41 = 4.39, P < 0.0001), and parents indicated a reduction in the frequency of aggression (CHI-Aggression, t44 = 2.82, P < 0.01) and hostility (CHI-Hostility, t44 = 4.93, P < 0.0001) in their children.

Conclusions:

The group program appeared to reduce children's anger and aggression. However, the results are preliminary, and further controlled evaluation is required.
Association between Antidepressant Use and Prescribing of Gastric Acid Suppressants
Authors: Ma Janice , Vaillancourt Régis , Boddam Randy , Auger Stéphane , Sampalis John
Published: January 2017

Objective:

To determine whether an increased risk of gastrointestinal events is present in younger, generally healthy adults who consume antidepressants.

Method:

We performed a retrospective cohort study using the pharmacy records of Canadian Forces (CF) members who received antidepressants between June 1997 and November 2002, excluding those taking bupropion for smoking cessation. The control cohort comprised members who received salbutamol. Changes in use of gastric acid–reducing agents (GARs) and incident GAR prescribing rates were compared pre- and postinitiation of target medications. We performed ogistic regression analyses to evaluate the effects of age, sex, and concomitant medication use on GAR prescribing.

Results:

A total of 8722 antidepressant exposures were identified among 5588 CF members. The control cohort consisted of 3059 people with 4154 salbutamol exposures. The number of incident GAR prescriptions decreased in both groups postexposure; however, the rate of decrease was significantly greater among salbutamol users (odds ratio 1.38; 95%CI, 1.12 to 1.71). Antidepressant users were significantly more likely to receive a new prescription for GAR following both short-term and long-term exposure (adjusted odds ratio 4.93; 95%CI, 2.66 to 9.21 and 2.83; 95%CI, 2.05 to 3.92, respectively). Antiplatelet agents, bisphosphonates, oral corticosteroids, and nonsteroidal antiinflammatory drugs were significant predictors of GAR prescription.

Conclusion:

Consistent with other reports, this study has identified that antidepressant use increases the risk for use of a gastric acid suppressant. Careful consideration should thus be made with regard to increased gastric event risk among antidepressant users.
Posttraumatic Stress Disorder and Health-Related Quality of Life among a Sample of Treatment- and Pension-Seeking Deployed Canadian Forces Peacekeeping Veterans
Authors: Richardson J Don , Long Mary E , Pedlar David , Elhai Jon D
Published: January 2017

Objectives:

To examine the health-related quality of life (HRQOL) in deployed Canadian Forces peacekeeping veterans, addressing associations with posttraumatic stress disorder (PTSD), and depression severity.

Methods:

Participants ( n = 125) were consecutive male veterans who were referred for a psychiatric assessment. Instruments administered included the Clinician-Administered PTSD Scale, Hamilton Depression Scale, Short-Form-36 Health Survey, and sociodemographic characteristics.

Results:

Mental HRQOL was significantly lower for peacekeepers with, than without, PTSD. Using univariate analyses, PTSD and depression severity were each significantly negatively related to mental HRQOL. In sequential regression analyses controlling for age, we found that PTSD and depression severity significantly predicted both mental and physical HRQOL.

Conclusions:

Veterans with PTSD have significant impairments in mental and physical HRQOL. This information is useful for clinicians and Veterans Affairs administrators working with the newer generation of veterans, as it stresses the importance of including measures of quality of life in the psychiatric evaluation of veterans to better address their rehabilitation needs.

Objectifs:

Examiner la qualité de vie liée à la santé (QDVLS) chez d'anciens combattants déployés des Forces canadiennes de maintien de la paix, en abordant les associations avec le trouble de stress post-traumatique (TSPT) et la gravité de la dépression.

Méthodes:

Les participants ( n = 125) étaient d'anciens combattants masculins consécutifs qui ont été adressés pour une évaluation psychiatrique. Les instruments administrés comprenaient l'échelle du TSPT administrée par un clinicien, l'échelle de dépression de Hamilton, le questionnaire sur la santé SF-36, et les caractéristiques sociodémographiques.

Résultats:

La qualité de vie liée à la santé mentale était significativement plus faible chez les gardiens de la paix qui souffraient du TSPT que chez ceux qui n'en étaient pas affectés. Les analyses univariées ont révélé que le TSPT et la gravité de la dépression étaient chacun significativement négativement liés à la QDVLS mentale. Dans les analyses de régression séquentielles contrôlant l'âge, nous avons observé que le TSPT et la gravité de la dépression prédisaient significativement la QDVLS tant physique que mentale.

Conclusions:

Les anciens combattants souffrant de TSPT ont des déficiences significatives de QDVLS. Cette information est utile aux cliniciens et aux administrateurs du ministère des Anciens combattants qui travaillent auprès des anciens combattants de la nouvelle génération, car elle souligne l'importance d'inclure des mesures de la qualité de vie dans l'évaluation psychiatrique des anciens combattants, afin de mieux répondre à leurs besoins en matière de réhabilitation.
Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Metaanalysis
Authors: Lam Raymond W , Chan Peter , Wilkins-Ho Michael , Yatham Lakshmi N
Published: January 2017

Objective:

Systematic reviews show that repetitive transcranial magnetic stimulation (rTMS) is superior to sham control conditions in patients with major depressive disorder, but the clinical relevance is not clear. None have specifically examined outcomes in patients with treatment-resistant depression (TRD).

Method:

A systematic review was conducted by identifying published randomized controlled trials of active rTMS, compared with a sham control condition in patients with defined TRD (that is, at least one failed trial). The primary outcome was clinical response as determined from global ratings, or 50% or greater improvement on a rating scale. Other outcomes included remission and standardized mean differences in end point scores. Metaanalysis was conducted for absolute risk differences using random effects models. Sensitivity and subgroup analyses were also conducted to explore heterogeneity and robustness of results.

Results:

A total of 24 studies ( n = 1092 patients) met criteria for quantitative synthesis. Active rTMS was significantly superior to sham conditions in producing clinical response, with a risk difference of 17% and a number-needed-to-treat of 6. The pooled response and remission rates were 25% and 17%, and 9% and 6% for active rTMS and sham conditions, respectively. Sensitivity and subgroup analyses did not significantly affect these results. Dropouts and withdrawals owing to adverse events were very low.

Conclusions:

For patients with TRD, rTMS appears to provide significant benefits in short-term treatment studies. However, the relatively low response and remission rates, the short durations of treatment, and the relative lack of systematic follow-up studies suggest that further studies are needed before rTMS can be considered as a first-line monotherapy treatment for TRD.