Notes on the conservation threats to the western lesser spot-nosed monkey (Cercopithecus petaurista buettikoferi) in the Bijagós Archipelago (Guinea-Bissau, West Africa).

The lesser spot-nosed monkey (Cercopithecus petaurista) is a widely distributed West African guenon, which is generally considered less vulnerable to local extinctions than many sympatric primate species. Guinea-Bissau harbours the westernmost populations of the species, which is thought to be very rare or even extinct on the mainland, but to have putative populations on some islands of the Bijagós Archipelago. However, due to a lack of regional studies, baseline information on these insular populations is missing. We collected baseline data on the anthropogenic activities that possibly threaten the long-term conservation of this primate by using non-systematic ethnographic methodologies. The species was reported to be decreasing in number or rare by locals on two of the islands, and we identified two main conservation threats to it: generalised habitat loss/degradation, and hunting. While subsistence hunting has been recorded before in these areas, we report, to the best of our knowledge for the first time for these islands, the presence of a semi-organised commercial wild meat trade. The carcasses of western lesser spot-nosed monkeys were observed being stored and shipped from seaports to be sold at urban hubs (Bissau and Bubaque Island). The effect of commercial trade on the species could be severe, considering the small, naturally occurring, carrying capacities typical of insular ecosystems. The results of this study highlight the importance of understanding the leading social drivers of wild meat hunting of lesser spot-nosed monkeys on the Bijagós Archipelago, and the need to conduct baseline research on these insular populations, for which qualitative and quantitative methods could be combined.

Markers of Cardiotoxicity in Early Breast Cancer Patients Treated With a Hypofractionated Schedule: A Prospective Study.

PURPOSE: To evaluate, in a series of early breast cancer (BC) patients treated with hypofractionated adjuvant radiotherapy (RT), whether N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I assay measurements can predict acute clinical or preclinical cardiotoxicity. PATIENTS AND METHODS: The study comprised 44 consecutive patients, who underwent conservative surgery with or without (neo)adjuvant chemotherapy and hypofractionated adjuvant RT. The RT schedule consisted in a total dose of 42.4 Gy in 16 fractions administered 5 days per week. Twenty-one patients received a subsequent boost to the tumor bed consisting of a total dose of 10 Gy in 4 fractions delivered via a direct electron field. All patients underwent 12-lead electrocardiogram, echocardiogram, and cardiac clinical examinations before RT to assess cardiovascular risk factors; these examinations were repeated yearly for 5 consecutive years. High-sensitivity cardiac troponin I and NT-proBNP were analyzed from serum samples at baseline, after delivery of the fourth and 16th RT fractions, and 12 months after treatment completion. RESULTS: No increase in cardiac troponin I and B-type natriuretic peptide levels related to left breast irradiation was observed. No statistical difference in NT-proBNP and high-sensitivity troponin I levels between left- and right-sided BC was found. An increase was observed of B-type natriuretic peptide levels at baseline, during treatment, and until 12 months after RT related to hypertension, with the P value near to the .05 threshold for age and chemotherapy. CONCLUSION: Conformational hypofractionated RT in left-sided BC may not cause acute myocardial damage. Early cardiac screening may be used to identify patients with cardiologic risk factors, patients who are older than 60 years, and patients who received chemotherapy that could result in clinically relevant cardiac pathologies.

Relapse of pemphigus vulgaris after topical application of ingenol mebutate.

Ingenol mebutate is a recently approved topical agent for the treatment of actinic keratosis. Its most common adverse effects are transient local skin reactions. We report a 63-year-old white man who presented with a red-brownish crusted plaque involving the dorsum of his nose and an eroded area on his lower lip, which appeared soon after topical application of ingenol mebutate gel. Clinical, histological and immunopathological features were consistent with a diagnosis of pemphigus vulgaris (PV). To our knowledge, this is the first report of relapse of PV after topical application of ingenol mebutate gel. The temporal relationship between the application of the drug and the outbreak of PV supports the involvement of this agent in triggering the disease. It is plausible that ingenol mebutate may have induced the disease by its action on the production of proinflammatory cytokines.

Environmental quality of the operating theaters in Campania Region: long lasting monitoring results.

BACKGROUND: The health risk level in the operating theaters is directly correlated to the safety level offered by the healthcare facilities. This is the reason why the national Authorities released several regulations in order to monitor better environmental conditions of the operating theaters, to prevent occupational injuries and disease and to optimize working conditions. For the monitoring of environmental quality of the operating theaters following parameters are considered: quantity of supplied gases, anesthetics concentration, operating theatres volume measurement, air change rate, air conditioning system and air filtration. The objective is to minimize the risks in the operating theaters and to provide the optimal environmental working conditions. This paper reports the environmental conditions of operating rooms performed for several years in the public hospitals of the Campania Region. METHODS: Investigation of environmental conditions of 162 operating theaters in Campania Region from January 2012 till July 2014 was conducted. Monitoring and analysis of physical and chemical parameters was done. The analysis of the results has been made considering specific standards suggested by national and international regulations. RESULTS: The study showed that 75% of the operating theaters presented normal values for microclimatic monitoring, while the 25% of the operating theaters had at least one parameter outside the limits. The monitoring of the anesthetics gases showed that in 9% of measurements of nitrous oxides and 4% of measurements of halogenated was not within the normal values.

Cutaneous melanoma in solid organ transplant patients.

Solid organ transplant patients are at greatly increased risk of developing a wide variety of skin cancers, particularly epithelial skin cancers. On the other hand, it is well known that an intact immune system limits the development of benign melanocytic lesions. The eruptive nevi phenomenon, which we can observe in solid organ transplant recipients, is indicative of the relationship between melanocyte proliferation and immune system. Regression of melanocytic nevi after restoration of complete immune responsiveness is a further clinical example the role of immunosurveillance on melanocyte proliferation. However, melanoma incidence in organ transplant recipients appears only 2-3 folds higher than in general population. To this regard, organ transplant recipients who develop de novo melanomas thicker than 2mm seem to have a significantly worse outcome with a greatly increased risk of dying of metastatic melanoma, whereas those who develop a ≤2 mm thickness melanoma seem to have a prognosis similar to that of the general population. Furthermore, there is no evidence supporting an increased risk of melanoma recurrences after transplant in patients with a history of low-risk melanoma. Melanoma is also one of the most frequent and lethal donor-derived malignancies suggesting that a history of invasive melanoma should be considered an absolute contraindication to donation. The aim of this review is to investigate the relationship between immunosuppression and melanoma and to discuss its clinical implications for the management of transplant-associated melanoma.

The kiwi fruit peptide kissper displays anti-inflammatory and anti-oxidant effects in in-vitro and ex-vivo human intestinal models.

Literature reports describe kiwi fruit as a food with significant effects on human health, including anti-oxidant and anti-inflammatory activity. Fresh fruit or raw kiwi fruit extracts have been used so far to investigate these effects, but the molecule(s) responsible for these health-promoting activities have not yet been identified. Kissper is a kiwi fruit peptide displaying pore-forming activity in synthetic lipid bilayers, the composition of which is similar to that found in intestinal cells. The objective of this study was to investigate the kissper influence on intestinal inflammation using cultured cells and ex-vivo tissues from healthy subjects and Crohn's disease (CD) patients. The anti-oxidant and anti-inflammatory properties of kissper were tested on Caco-2 cells and on the colonic mucosa from 23 patients with CD, by challenging with the lipopolysaccharide from Escherichia coli (EC-LPS) and monitoring the appropriate markers by Western blot and immunofluorescence. EC-LPS challenge determined an increase in the intracellular concentration of calcium and reactive oxygen species (ROS). The peptide kissper was highly effective in preventing the increase of LPS-induced ROS levels in both the Caco-2 cells and CD colonic mucosa. Moreover, it controls the calcium increase, p65-nuclear factor (NF)-kB induction and transglutaminase 2 (TG2) activation inflammatory response in Caco-2 cells and CD colonic mucosa. Kissper efficiently counteracts the oxidative stress and inflammatory response in valuable model systems consisting of intestinal cells and CD colonic mucosa. This study reports the first evidence supporting a possible correlation between some beneficial effects of kiwi fruit and a specific protein molecule rather than generic nutrients.

To be or not to be translational.

Translational Research means different things to different people, but it seems crucial to almost everyone. This discipline, although defined differently in academia, regulatory institutions, and industry, shares the fundamental vision of Translational Medicine, which efficiently and effectively translates basic scientific findings relevant to human disease into knowledge that benefits patients. In the present perspective, we collected commentaries and descriptions about Translational Medicine to stimulate discussion and better understand what Translational Medicine is.

Current practice and recent advances in pediatric pain management.

BACKGROUND: Differently from the adult patients, in pediatric age it is more difficult to assess and treat efficaciously the pain and often this symptom is undertreated or not treated. In children, selection of appropriate pain assessment tools should consider age, cognitive level and the presence of eventual disability, type of pain and the situation in which it is occurring. Improved understanding of developmental neurobiology and paediatric analgesic drugs pharmacokinetics should facilitate a better management of childhood pain. AIM: The objective of this review is to discuss current practice and recent advances in pediatric pain management. METHODS: Using PubMed we conducted an extensive literature review on pediatric pain assessment and commonly used analgesic agents from January 2000 to January 2012. CONCLUSIONS: A multimodal analgesic regimen provides better pain control and functional outcome in children. Cooperation and communication between the anaesthesiologist, surgeon, and paediatrician are essential for successful anaesthesia and pain management.

Progressive increase of glucose transporter-3 (GLUT-3) expression in estrogen-induced breast carcinogenesis.

INTRODUCTION: Increased glucose uptake and glycolysis are main metabolic characteristics of malignant cells. A family of glucose transporters (GLUTs) facilitates glucose movement across the plasma membranes in a tumor-specific manner. Glucose transporter-1 (GLUT-1), GLUT-3 and recently GLUT-12, have been previously shown in breast cancer cells and are found to be associated with poor prognosis. In addition, it has been shown that estrogen plays critical roles in GLUT regulation, however, the stage-specific GLUT regulation of mammary carcinogenesis is unclear. METHODS: GLUT expression patterns were investigated in an in vitro-in vivo progressive, estrogen-induced, mammary carcinogenesis model which consisted of four cell lines, with same genetic background. In this model, different stages of tumor initiation and progression are represented, MCF-10F being the normal stage, E2 cells the transformed stage by estrogen, C5 cells, the invasive stage, and T4 cells the tumorigenic stage. In addition, loss of ductulogenesis and solid mass formation in collagen matrix and invasiveness of the cells were counted. RESULTS: Real time PCR showed that GLUT1 expression was downregulated in MCF10F after treatment with 17ß-estradiol (E2), and in the invasive cell type (C5), but not in the tumor cells (T4), which had no changes compared to MCF10F. C5 and T4 cells showed the highest rate of GLUT-3 expression. These cells were also found to be associated with loss of ductulogenesis, solid mass formation and higher invasive capacity, whereas, GLUT-12 was downregulated in C5 and T4 cells. CONCLUSION: Estrogen-induced malignant transformation is associated with remarkable and progressive GLUT-3 expression, GLUT-1 re-expression at further stages, as well as GLUT-12 downregulation.

CD30+ lymphoproliferative disorders of the skin: still an open question.

CD30+ lymphoproliferative disorders of the skin represent a well-defined spectrum of primary cutaneous T-cell lymphomas. They include lymphomatoid papulosis and cutaneous anaplastic large-cell lymphoma which are characterized by the common expression of the CD30 antigen, but different clinical, histological and molecular features. Recent progress in the pathobiology and identification of therapeutic targets has contributed to our current understanding of this peculiar group of cutaneous lymphoproliferative disorders. The characteristic features of this group of cutaneous lymphoproliferative disorders are reviewed with particular emphasis to their diagnosis and treatment strategies.

Human parvovirus B 19 and Epstein-Barr virus co-infection in a child with hereditary spherocytosis.

BACKGROUND: In patients with chronic congenital haemolytic disorders, human Parvovirus B19 (HPV B19) is frequently involved in pure red-cell aplastic crises. Furthermore, it may inhibit three-lineage haematopoiesis in the bone marrow, causing severe pancytopenia. In such patients, Epstein Barr virus (EBV) infection also seems to share the same mechanism as HPV B19 in inducing bone marrow aplasia, but at present the clinical effect of an infection sustained by both viruses is unknown. CLINICAL REPORT: We present a 7-year-old boy affected by hereditary spherocytosis (HS) who suffered from transient aplastic crisis, in whom laboratory findings revealed a double HPV B19 and EBV infection. CONCLUSIONS: To our knowledge, this is the first report of a case of HPV B19 and EBV co-infection diagnosis in a paediatric patient. Despite underlying HS, no signs of haemolytic anaemia were detected, but the infection only produced transient pancytopenia. Nevertheless, the reason why there was no additive effect of the two viruses on the aplastic crisis is still unclear.

Assessment of the dietary habits and polycyclic aromatic hydrocarbon exposure in primary school children.

Thirty Italian children, 7-9 year aged, living in Naples were investigated on their dietary habits and on polycyclic aromatic hydrocarbon (PAH) exposure by a food diary-questionnaire and one week duplicate diet sample analyses. Daily total food consumption mean value was 632 +/- 215 g day(-1), median value 613 g day(-1). The daily energy intake and the diet composition meanly agreed with the official guidelines for the Italian children. Sixteen PAHs were simultaneously detected and, according to the European Food Safety Authority (EFSA) approach, benzo[a]pyrene; benzo[a]pyrene + chrysene (PAH2); PAH2 + benz[a]anthracene + benzo[b]fluoranthene (PAH4); PAH4 + benzo[k]fluoranthene + benzo[ghi]perylene + dibenz[a, h]anthracene + indeno[1,2,3-cd]pyrene (PAH8) were considered in evaluating the children's dietary exposure to PAHs. The benzo[a]pyrene (BaP) median concentrations in foods varied from 0.06 to 0.33 microg kg(-1). Only three samples of cooked foods (one fish and two meat samples) exceeded legal limits fixed by the European Union for BaP. Daily median intakes of benzo[a]pyrene, PAH2, PAH4, and PAH8 were 153; 318; 990; 1776 ng day(-1); their median exposure values were 5; 10; 28; 54 ng kg(-1) bw day(-1). The Margins of Exposure (MOEs) in median consumers agreed with the EFSA safety values except for PAH8.

In ataxia-teleangiectasia betamethasone response is inversely correlated to cerebellar atrophy and directly to antioxidative capacity.

BACKGROUND AND PURPOSE: Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by alterations of the A-T mutated (ATM) gene. Although A-T is a non-curable disease, we, previously, documented a clear improvement of cerebellar functions during a short-term betamethasone trial. The aim of this study was to define the underlying biochemical mechanism. METHODS: In six A-T patients receiving a short-term steroid therapy, intracellular glutathione (GSH) levels were evaluated with a colorimetric assay. The lipid peroxidation level and reactive oxygen species (ROS) production were evaluated using commercial assays. All the parameters were compared with the improvement of cerebellar functions expressed as delta (Delta) of the Scale for the Assessment and Rating of Ataxia (SARA). RESULTS: We observed an inverse correlation between Delta SARA and the severity of cerebellar atrophy and between the latter and basal GSH values. Four of the five patients with the highest Delta SARA also had the highest GSH values. Moreover, even though basal ROS values were comparable in patients and controls, in the only patient studied at different time-points of therapy, a remarkable reduction in ROS levels was documented. CONCLUSION: We suggest that antioxidative mechanisms play a role in favouring the improvement of cerebellar functions observed in A-T patients receiving a short-term betamethasone trial.

Efficacy of budesonide therapy in the early phase of treatment of adult coeliac disease patients with malabsorption: an in vivo/in vitro pilot study.

1. Budesonide is a glucocorticosteroid with a local anti-inflammatory effect. Coeliac disease is an immune-mediated disease caused by gluten ingestion in intolerant patients. The aim of the present study was to investigate the efficacy of budesonide in malabsorptive coeliac patients and its effect in an in vitro gliadin challenge. 2. Twenty coeliac patients with malabsorption were enrolled in the present study and were randomly assigned to one of two 4 week treatments: (i) a gluten-free diet alone; or (ii) a gluten-free diet plus 6 mg budesonide daily. At the end of 4 weeks treatment, all patients underwent clinical evaluation, laboratory tests and self-evaluation of well-being using a visual analogue scale. Intestinal biopsies from five coeliac patients (selected randomly) and four non-coeliac disease controls who underwent upper endoscopy for intestinal bleeding were challenged with gliadin (0.5 mg/mL) and budesonide (10-30 microg/mL) for 3 and 24 h. Biopsies were tested by immunohistochemistry and immunofluorescence for known markers of inflammation. 3. Treatment of patients with 6 mg budesonide daily for 4 weeks resulted in increased bodyweight, a decreased number of evacuations and decreased stool weight compared with patients on a gluten-free diet alone for 4 weeks. Well-being scores were higher in patients treated with both a gluten-free diet and budesonide compared with those receiving a gluten-free diet alone. 4. In vitro studies showed that budesonide reduced epithelial tyrosine phosphorylation and expression of histocompatibility leucocyte antigen complex DR (HLA-DR) elicited by gliadin-derived peptides. In addition, the expression of cyclo-oxygenase (COX)-2 and intercellular adhesion molecule (ICAM)-1 in the lamina propria was reduced in patients treated with both gliadin and budesonide compared with patients treated with gliadin alone. Budesonide alone decreased HLA-DR in crypt enterocytes, as well as ICAM-1 and COX-2 expression in the lamina propria of biopsy specimen of coeliac patients. Budesonide had no effect in control samples. 5. In conclusion, the results of the present study indicate that budesonide shows efficacy in the treatment of symptoms in adult coeliac patients with overt malabsorption. The mechanism underlying the effects of budesonide in reducing symptoms was elucidated by in vitro studies involving a gliadin challenge.

Platelet dysfunction in central obesity.

Central obesity is a relevant risk factor for major cardiovascular events due to the atherosclerotic involvement of coronary, cerebral and lower limb arterial vessels. A major role in the increased cardiovascular risk is played by platelets, which show an increased activation and a reduced sensitivity to the physiological and pharmacological antiaggregating agents. This review focuses on platelet dysfunction in central obesity. The mechanisms involved are related to: i) the reduced sensitivity to insulin and other substances acting via intracellular cyclic nucleotides, such as nitrates and prostacyclin; ii) the altered intracellular ionic milieu with elevated cytosolic Ca(2+); and iii) the increased oxidative stress, which elicits isoprostane production from arachidonic acid. Therapeutic guidelines recommend a multifactorial prevention of cardiovascular disease including antiplatelet drugs in high risk patients, even though, at present, the protective effect of antiplatelet therapy in obese, insulin resistant subjects has not been evaluated by specific trials. Some reports, however, suggest a decreased sensitivity to the antiaggregating effects of both acetylsalicylic acid (aspirin) and thienopyridines in human obesity. Platelet defects may play a pivotal role in the reduced efficacy of antiplatelet therapy in obese subjects in the setting of cardiovascular prevention and acute coronary syndrome treatment. Thus, a specifically tailored antiaggregating therapy is likely necessary in obese, insulin resistant subjects, especially in the presence of type 2 diabetes mellitus.

FOXN1 homozygous mutation associated with anencephaly and severe neural tube defect in human athymic Nude/SCID fetus.

The forkhead, Fox, gene family comprises a diverse group of 'winged-helix' transcription factors that play important roles in development, metabolism, cancer and aging. Recently, several forkhead genes have been demonstrated to play critical roles in lymphocyte development and effector functions. Alterations of the FOXN1 gene in both mice and humans result in a severe combined immunodeficiency caused by an intrinsic defect of the thymus associated with congenital alopecia (Nude/severe combined immunodeficiency phenotype). FOXN1 is a member of the class of proteins involved in the development and differentiation of the central nervous system. We identified a human fetus homozygous for a mutation in FOXN1 gene who lacked the thymus and also had abnormal skin, anencephaly and spina bifida. Moreover, we found that FOXN1 gene is expressed in mouse developing choroid plexus. These observations suggest that FOXN1 may be involved in neurulation in humans.

Steroid-induced improvement of neurological signs in ataxia-telangiectasia patients.

A recent clinical observation reported on a dramatic improvement of neurological symptoms following short-term betamethasone administration in a child affected with ataxia-teleangiectasia (A-T). The aim of this study was to extend this observation to additional A-T patients followed at a single Immunodeficiency Center. Six consecutive patients (three males; mean age 16.3 years, range 5-30 years) were enrolled into this monocentric before-after trial. A cycle of oral betamethasone at the dosage of 0.1 mg/kg/day was administered for 10 days. The neurological evaluation was performed through the Scale for the Assessment and Rating of Ataxia. Overall, five of the six patients exhibited a clear amelioration of the neurological performances. Only in two patients, a slight amelioration persisted 7 days after the therapy withdrawal, whilst in the other patients the score reached approximately the pre-treatment value at the end of the therapy. Twenty-eight of the 46 evaluated neurological items (60%) improved during therapy. The speech disturbance, finger chase and nose-finger test showed the more significant improvement. The clinical amelioration was inversely correlated with the level of cerebellum atrophy, as revealed by the magnetic resonance. Our data indicate that neurological signs in A-T are susceptible of beneficial pharmacological intervention even years after the disease onset.

Resistance to the nitric oxide/cyclic guanosine 5'-monophosphate/protein kinase G pathway in vascular smooth muscle cells from the obese Zucker rat, a classical animal model of insulin resistance: role of oxidative stress.

Some in vivo and ex vivo studies demonstrated a resistance to the vasodilating effects of nitric oxide (NO) in insulin-resistant states and, in particular, obese Zucker rats (OZR). To evaluate the biochemical basis of this phenomenon, we aimed to identify defects of the NO/cGMP/cGMP-dependent protein kinase (PKG) pathway in cultured vascular smooth muscle cells (VSMCs) from OZR and lean Zucker rats (LZR) by measuring: 1) NO donor ability to increase cGMP in the absence and presence of inhibitors of soluble guanylate cyclase (sGC) and phosphodiesterases (PDEs); 2) NO and cGMP ability to induce, via PKG, vasodilator-stimulated phosphoprotein (VASP) phosphorylation at serine 239 and PDE5 activity; 3) protein expression of sGC, PKG, total VASP, and PDE5; 4) superoxide anion concentrations and ability of antioxidants (superoxide dismutase+catalase and amifostine) to influence the NO/cGMP/PKG pathway activation; and 5) hydrogen peroxide influence on PDE5 activity and VASP phosphorylation. VSMCs from OZR vs. LZR showed: 1) baseline cGMP concentrations higher, at least in part owing to reduced catabolism by PDEs; 2) impairment of NO donor ability to increase cGMP, even in the presence of PDE inhibitors, suggesting a defect in the NO-induced sGC activation; 3) reduction of NO and cGMP ability to activate PKG, indicated by the impaired ability to phosphorylate VASP at serine 239 and to increase PDE5 activity via PKG; 4) similar baseline protein expression of sGC, PKG, total VASP, and PDE5; and 5) higher levels of superoxide anion. Antioxidants partially prevented the defects of the NO/cGMP/PKG pathway observed in VSMCs from OZR, which were reproduced by hydrogen peroxide in VSMCs from LZR, suggesting the pivotal role of oxidative stress.

Breast cancer prevention.

We have developed a new approach for breast cancer prevention, capitalizing in the preventive effect of early first full-term pregnancy, hormonally induced differentiation and our ability to identify specific genomic signatures that allow us to predict risk reduction. Early pregnancy imprints in the breast permanent genomic changes or a 'signature' that reduces the susceptibility of this organ to cancer. At cellular level, what we have achieved is the shifting of the Stem Cell 1 population, highly susceptible to cancer, to a population of Stem Cell 2 that is refractory to carcinogenesis. In a case-control study, we have compared the gene expression profile in normal breast tissue from nulliparous and parous postmenopausal women with (case) and without (control) breast cancer. We have determined that early first full-term pregnancy induces a specific genomic signature in the postmenopausal breast that is the biomarker for the Stem cell 2. The Stem cell 2 contains specific genes controlling transcription, RNA processing, immune response, apoptosis and DNA repair. We have further detected in the plasma, using an ELISA assay, the proteins coded by the gene signature. We are developing clinical trials to demonstrate the proof of the principle that r-hCG can induce in the human breast a genomic signature of the Stem cell 2. This is a concept that challenges the currently available chemopreventive agents that need to be given for extended periods for maintaining the suppression of a specific metabolic pathway or the abrogation of the function of an organ.