Unexpected slow recovery of seagrass leaf epiphytes after the impact of a summer heat wave and concomitant mucilage bloom.

The epiphytes of seagrass leaves constitute a peculiar community, comprised of a number of species specialized for this living substrate. Several studies report on the response of epiphytes to different pressures but no information exists about the effects of summer heatwaves, which have become frequent events in the last decades. This paper represents the first attempt to investigate the change in the leaf epiphyte community of the Mediterranean seagrass Posidonia oceanica due to the heatwave occurred in summer 2003. Thanks to a series of data collected seasonally between 2002 and 2006, and punctual data in the summers of 2014 and 2019, we assessed the change over time in the leaf epiphyte community. Temperature data trends were analysed through linear regression, while multivariate analyses (i.e., nMDS and SIMPER) were applied to cover data in order to assess changes over time in the epiphyte community. As a whole, the two most abundant taxa were the crustose coralline alga Hydrolithon and the encrusting bryozoan Electra posidoniae, which displayed the highest average cover values in summer (around 19%) and spring (around 9%), respectively. Epiphytes proved to be sensitive to temperature highs, displaying different effects on cover, biomass, diversity and community composition. Cover and biomass exhibited a dramatic reduction (more than 60%) after the disturbance. In particular, Hydrolithon more than halved, while E. posidoniae dropped sevenfold during summer 2003. While the former recovered comparatively quickly, the latter, as well as the whole community composition, apparently required 16 years to return to a condition similar to that of 2002.

Geometric border as a marker for melanoma diagnosis: Study of 200 consecutive melanocytic lesions.

The ABCD rule has long been proposed as a guidance for malignant melanoma (MM) diagnosis. We aimed to define a new simple, straightforward tool that could be useful in early melanoma detection and must be validated in further studies. We conducted a prospective historic cohort study of 200 melanocytic lesions classifying them according to the presence of geometric borders. Sixty-four percent of the MM and 31% of the melanocytic nevi presented with geometric borders. Lesions with two straight borders that formed a noncurvilinear angle presented a 2.1-fold higher risk of being malignant after excision. When comparing melanomas with geometric and nongeometric border, we found a tendency toward better prognostic markers in the geometric lesions. Lesions located in the extremities and melanoma subtype SSM were more common in the geometric group. Regarding pathologic features, a deeper Breslow (mean, 3.8 vs 1.4 mm), presence of ulceration (25% vs 5%) and a higher number of mitosis was found in the nongeometric group. On the other hand, more regression was found in the geometric group while both groups showed similar degree of lymphovascular infiltration. We propose geometric border as another clinical criterion to take into account when suspecting MM, which must be validated in further studies. The ABCDE rule could be completed with a G for geometry.

Mohs Surgery Outside Usual Indications: A Review.

The body of literature supporting the use of Mohs micrographic surgery (MMS) in tumors outside the main indications (basal cell carcinoma, squamous cell carcinoma, dermatofibrosacroma protuberans, lentigo maligna) is constantly growing, but it is still based on case reports, case series, or at best institutional case series that focus on a single malignancy. Our aim in this review was to assess use of MMS in an array of rare tumors outside the usual indications. A review was performed using the MEDLINE database and the search engine ClinicalKey®. We reviewed the use of MMS on atypical fibroxanthoma (AFX)/malignant fibrous histiocytoma, microcystic adnexal carcinoma, extramammary Paget's disease, Merkel cell carcinoma, pocrine/eccrine carcinoma/porocarcinoma, trichilemmal carcinoma, leiomyosarcoma, and angiosarcoma. Mohs micrographic surgery appears to be scarcely used in these tumors due to their low incidence. It is mainly performed for tumors in the H-zone of the face, and can be performed safely. The overall recurrence rate is lower compared with simple or wide local excision. MMS should be used in a more generalized fashion for these tumors.

Could JC virus be linked to chronic idiopathic intestinal pseudo-obstruction?

JC virus is a member of the Polyomavirus family, infects humans worldwide, and 90% of the population carry antibodies to the virus by adult life. The initial infection is asymptomatic, but it may become persistent. JC virus DNA is frequently present in the upper and lower gastrointestinal tracts of healthy adults. Chronic idiopathic intestinal pseudo-obstruction, one of the most severe gastrointestinal motility disorders, is a condition characterized by a clinical picture mimicking small bowel occlusion with related symptoms and signs in the absence of demonstrable mechanical obstruction. Because of the known neuropathic capability of this virus, and its frequent presence in the gut, it has been proposed that JCV might be detectable in tissues of patients with chronic idiopathic intestinal pseudo-obstruction, and possibly be involved in the pathogenesis of this disease, because the virus may actively infect the enteroglial cells of the myenteric plexuses of the patients with chronic idiopathic intestinal pseudo-obstruction. We report two cases of upper idiopathic intestinal pseudo-obstruction associated with JCV infection.

Investigación traslacional en psiquiatría: el marco Research Domain Criteria (RDoC) / Translational research in psychiatry: The Research Domain Criteria Project (RDoC)

Pese al éxito (o consenso) conseguido en la homogeneización de criterios clínicos por los sistemas de clasificación psiquiátrica categoriales (DSM y CIE), su validez y utilidad, clínica y en investigación, son cuestionables. En este artículo de revisión presentamos el marco Criterios de Investigación por Dominios (Research Domain Criteria, RDoC) como una alternativa para la investigación traslacional en psiquiatría. El marco de investigación traslacional RDoC sistematiza dianas y métodos de investigación en psiquiatría. RDoC parte de un catálogo de bases neurofuncionales de la conducta y plantea la psicopatología como la expresión fenotípica de las alteraciones en dichas funciones. Estas se clasifican en 5sistemas psicobiológicos. Los constructos funcionales se validan mediante evidencia proveniente de estudios básicos en 7 niveles de análisis: genes, moléculas, células, circuitos nerviosos, fisiología, conducta y autoinformes. Frente a los sistemas categoriales centrados en el diagnóstico, RDoC propone centrar el estudio de la psicopatología como correlato de alteraciones funcionales detectables, biológicas y comportamentales. RDoC es un marco de investigación que vincula el sustrato biológico con las manifestaciones fenotípicas, para llegar a una nosología psiquiátrica útil para guiar el tratamiento. Pese a que los hallazgos de RDoC no articulan un modelo concreto de guía para la práctica clínica, es un sistema de transición útil para crear hipótesis de investigación clínica, básica y epidemiológica

Despite the consensus achieved in the homogenization of clinical criteria by categorical psychiatric classification systems (DEM and CIE), they are criticized for a lack of validity and inability to guide clinical treatment and research. In this review article we introduce the Research Domain Criteria (RDoC) framework as an alternative framework for translational research in psychiatry. The RDOC framework systematizes both research targets and methodology for research in psychiatry. RDoC is based on a catalogue of neurobiological and neurocognitive evidence of behaviour, and conceives psychopathology as the phenotypic expression of alterations of functional domains that are classified into 5psychobiological systems. The RdoC framework also proposes that domains must be validated with evidence in 7levels of analysis: genes, molecules, cells, nerve circuits, physiology, behaviour and self-reports. As opposed to categorical systems focused on diagnosis, RDoC focuses on the study of psychopathology as a correlate of detectable functional, biological and behavioural disruption of normal processes. In order to build a useful psychiatric nosology for guiding clinical interventions, the RDoC research framework links the neurobiological basis of mental processes with phenotypical manifestations. Although the RDoC findings have not yet been articulated into a specific model for guiding clinical practice, they provide a useful transition system for creating clinical, basic and epidemiological research hypotheses

Translational research in psychiatry: The Research Domain Criteria Project (RDoC). / Investigación traslacional en psiquiatría: el marco Research Domain Criteria (RDoC).

Despite the consensus achieved in the homogenization of clinical criteria by categorical psychiatric classification systems (DEM and CIE), they are criticized for a lack of validity and inability to guide clinical treatment and research. In this review article we introduce the Research Domain Criteria (RDoC) framework as an alternative framework for translational research in psychiatry. The RDOC framework systematizes both research targets and methodology for research in psychiatry. RDoC is based on a catalogue of neurobiological and neurocognitive evidence of behaviour, and conceives psychopathology as the phenotypic expression of alterations of functional domains that are classified into 5psychobiological systems. The RdoC framework also proposes that domains must be validated with evidence in 7levels of analysis: genes, molecules, cells, nerve circuits, physiology, behaviour and self-reports. As opposed to categorical systems focused on diagnosis, RDoC focuses on the study of psychopathology as a correlate of detectable functional, biological and behavioural disruption of normal processes. In order to build a useful psychiatric nosology for guiding clinical interventions, the RDoC research framework links the neurobiological basis of mental processes with phenotypical manifestations. Although the RDoC findings have not yet been articulated into a specific model for guiding clinical practice, they provide a useful transition system for creating clinical, basic and epidemiological research hypotheses.

Is Epstein-Barr virus infection associated with the pathogenesis of microscopic colitis?

BACKGROUND: Epstein-Barr virus (EBV) has been associated with inflammation in the colon, particularly in patients with inflammatory bowel disease (IBD). Even if a relevant plasmocytosis, similar to IBD, is present in microscopic colitis (MC), the frequency of EBV infection in this setting is unknown. OBJECTIVES: We aimed to compare the frequency of colonic EBV infection in patients with MC, ulcerative colitis (UC), and irritable bowel syndrome (IBS). STUDY DESIGN: The frequency of colonic EBV infection in biopsies of 30 patients with MC, 30 patients with UC, and 30 controls with IBS was retrospectively assessed. PCR was performed to detect viral EBV DNA in colonic biopsies. In situ hybridization was also performed to identify and localize EBV-encoded small RNA1 and 2 (EBERs) within cells. RESULTS: The presence of EBV DNA was detected in 27 out of 30 MC patients, in 20 out of 30 UC cases, and in none of IBS group. The frequency of EBV DNA in MC was significantly higher compared with that reported in UC (90.0% vs. 66.7%, p=0.03). EBERs+ cells were observed in 18 out of 30 MC patients, in only 3 out of 30 UC patients (60.0% vs. 10.0%, p<0.001), and in none of IBS group. CONCLUSIONS: EBV infection is almost always detectable in the colonic mucosa of patients with MC. Further studies are necessary to confirm this association and to clarify the role of EBV in MC and, more generally, in colonic inflammation.

JC Virus and Lung Adenocarcinoma: Fact or Myth?

BACKGROUND/AIM: An association has been reported between lung cancer and John Cunningham (JC) virus infection. The aim of this study was to evaluate the prevalence of JC virus in a small cohort of patients with lung adenocarcinoma and assess its presence in nodal metastasis. MATERIALS AND METHODS: Consecutive samples of 13 surgically-removed lung tumors and 13 surrounding normal cancer-free tissues were selected. Five cases included metastatic lymph nodes. JC virus infection was assessed through nested PCR. RESULTS: Seven out of thirteen patients with lung adenocarcinoma had a positive PCR test for JC virus. One of the five patients with nodal metastasis had a positive PCR test for JC virus. None of the thirteen specimens from the control group presented with JC virus infection. The difference between the two groups regarding JC virus infection was statistically significant (p=0.008). CONCLUSION: Our study suggests that JC virus might be involved in lung carcinogenesis.

Pemphigus foliaceus worsened by drugs in a patient with psoriasis, responding to adalimumab.

Pemphigus foliaceus is a blistering autoimmune disease related to the production of autoantibodies against desmoglein 1. We present a patient with psoriasis and pemphigus foliaceus aggravated by enalapril and amlodipine intake, with successful response of both conditions to adalimumab therapy.

El pénfigo foliáceo es una enfermedad autoinmune ampollosa debida a la producción de autoanticuerpos frente a la desmogleína 1. Presentamos el caso de un paciente con psoriasis y pénfigo foliáceo agravado por enalapril y amlodipino, con buena respuesta de ambas patologías a la terapia con adalimumab.Pemphigus foliaceus is a blistering autoimmune disease related to the production of autoantibodies against desmoglein 1. We present a patient with psoriasis and pemphigus foliaceus aggravated by enalapril and amlodipine intake, with successful response of both conditions to adalimumab therapy.

El pénfigo foliáceo es una enfermedad autoinmune ampollosa debida a la producción de autoanticuerpos frente a la desmogleína 1. Presentamos el caso de un paciente con psoriasis y pénfigo foliáceo agravado por enalapril y amlodipino, con buena respuesta de ambas patologías a la terapia con adalimumab.

Toxic megacolon and human Cytomegalovirus in a series of severe ulcerative colitis patients.

BACKGROUND: Human Cytomegalovirus (HCMV) infection has been reported to be a cause of refractory ulcerative colitis (UC). Toxic megacolon (TM) is a rare but severe complication of an acute attack of UC. OBJECTIVES: Aim of this study is to evaluate in a case-control study the association between HCMV and TM. STUDY DESIGN: All patients who were admitted at Medicine Department of V. Cervello Hospital in Palermo (tertiary referral center) for a severe UC flare-up complicated by the onset of TM (diameter of the transverse colon>6 cm) between January 1990 and November 2011 were identified through the electronic database. A total of 24 consecutive patients (16 male/8 female) with TM were identified. Each case of TM were individually matched by sex, age, extent of the underlying disease to 24 severe UC controls who did not develop TM. A further non matched control population of 48 severe UC was included. Haematoxilin and eosin stain, immunohistochemical procedure and nested polymerase chain reaction were performed to detect HCMV genes and proteins on rectal biopsies or surgical specimens. Pp65 antigenemia was performed in order to diagnose any possible systemic infection. HCMV frequency was compared between patients with and without TM during follow-up, using Fisher's Exact test. RESULTS AND CONCLUSIONS: HCMV was detected in histological specimens of 11 patients (46%) with TM compared to 2 (9%) severe UC matched controls (P = 0.0078) and 7 (14%) unmatched controls (p = 0,003). In severe colitis the presence of HCMV is more frequently associated with TM.

Mutations in a TGF-ß ligand, TGFB3, cause syndromic aortic aneurysms and dissections.

BACKGROUND: Aneurysms affecting the aorta are a common condition associated with high mortality as a result of aortic dissection or rupture. Investigations of the pathogenic mechanisms involved in syndromic types of thoracic aortic aneurysms, such as Marfan and Loeys-Dietz syndromes, have revealed an important contribution of disturbed transforming growth factor (TGF)-ß signaling. OBJECTIVES: This study sought to discover a novel gene causing syndromic aortic aneurysms in order to unravel the underlying pathogenesis. METHODS: We combined genome-wide linkage analysis, exome sequencing, and candidate gene Sanger sequencing in a total of 470 index cases with thoracic aortic aneurysms. Extensive cardiological examination, including physical examination, electrocardiography, and transthoracic echocardiography was performed. In adults, imaging of the entire aorta using computed tomography or magnetic resonance imaging was done. RESULTS: Here, we report on 43 patients from 11 families with syndromic presentations of aortic aneurysms caused by TGFB3 mutations. We demonstrate that TGFB3 mutations are associated with significant cardiovascular involvement, including thoracic/abdominal aortic aneurysm and dissection, and mitral valve disease. Other systemic features overlap clinically with Loeys-Dietz, Shprintzen-Goldberg, and Marfan syndromes, including cleft palate, bifid uvula, skeletal overgrowth, cervical spine instability and clubfoot deformity. In line with previous observations in aortic wall tissues of patients with mutations in effectors of TGF-ß signaling (TGFBR1/2, SMAD3, and TGFB2), we confirm a paradoxical up-regulation of both canonical and noncanonical TGF-ß signaling in association with up-regulation of the expression of TGF-ß ligands. CONCLUSIONS: Our findings emphasize the broad clinical variability associated with TGFB3 mutations and highlight the importance of early recognition of the disease because of high cardiovascular risk.

Could JC virus provoke metastasis in colon cancer?

AIM: To evaluate the prevalence of John Cunningham virus (JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis. METHODS: Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ(2) test. RESULTS: Four out of 19 patients with colon cancer had a positive polymerase chain reaction (PCR) test for JC virus, and four had liver metastasis. Among the patients with liver metastasis, three out of four had a positive PCR test for JC virus in the surgical specimen and in the liver biopsy; the only patient with liver metastasis with a negative test for JC virus also presented a negative test for JC virus in the surgical specimen. In the control group of patients with hepatitis C infection, none of the ten patients presented JC virus infection in the hepatic biopsy. The difference between the two groups regarding JC virus infection was statistically significant (χ(2) = 9.55, P = 0.002). CONCLUSION: JC virus may play a broader role than previously thought, and may be mechanistically involved in the late stages of these tumors.

CMV infection associated with severe lung involvement and persistent pulmonary hypertension of the newborn (PPHN) in two preterm twin neonates.

The diagnosis of congenital CMV is usually guided by a number of specific symptoms and findings. Unusual presentations may occur and diagnosis is challenging due to uncommon or rare features. Here we report the case of two preterm, extremely low birthweight, 28-week gestational age old twin neonates with CMV infection associated with severe lung involvement and persistent pulmonary hypertension of the newborn (PPHN). They were born to a HIV-positive mother, hence they underwent treatment with zidovudine since birth. Both infants featured severe refractory hypoxemia, requiring high-frequency ventilation, inhaled nitric oxide and inotropic support, with full recovery after 2 months. Treatment with ganciclovir was not feasible due the concomitant treatment with zidovudine and the risk of severe, fatal toxicity. Therefore administration of intravenous hyperimmune anti-CMV immunoglobulin therapy was initiated. Severe lung involvement at birth and subsequent pulmonary hypertension are rarely described in preterm infants as early manifestations of CMV congenital disease. In the two twin siblings here described, the extreme prematurity and the treatment with zidovudine likely worsened immunosuppression and ultimately required a complex management of the CMV-associated lung involvement.

Use of erythropoietin is associated with threshold retinopathy of prematurity (ROP) in preterm ELBW neonates: a retrospective, cohort study from two large tertiary NICUs in Italy.

BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial disease with evidence of many associated risk factors. Erythropoietin has been reported to be associated with this disorder in a murine model, as well as in humans in some single-center reports. We reviewed the data from two large tertiary NICUs in Italy to test the hypothesis that the use of erythropoietin may be associated with the development of the most severe stages of ROP in extremely low birth weight (ELBW) neonates. DESIGN/METHODS: Retrospective study by review of patient charts and eye examination index cards on infants with birth weight <1000g admitted to two large tertiary NICUs in Northern Italy (Sant'Anna Hospital NICU in Torino, and Ca' Foncello Hospital Neonatology in Treviso) in the years 2005 to 2007. Standard protocol of administration of EPO in the two NICUs consisted of 250 UI/kg three times a week for 6-week courses (4-week in 1001-1500g infants). Univariate analysis was performed to assess whether the use of EPO was associated with severe (threshold) ROP. A control, multivariate statistical analysis was performed by entering into a logistic regression model a number of neonatal and perinatal variables that - in univariate analysis - had been associated with threshold ROP. RESULTS: During the study period, 211 ELBW infants were born at the two facilities and survived till discharge. Complete data were obtained for 197 of them. Threshold retinopathy of prematurity occurred in 26.9% (29 of 108) of ELBW infants who received erythropoietin therapy, as compared with 13.5% (12 of 89) of those who did not receive erythropoietin (OR 2.35; 95% CI 1.121-4.949; p=0.02 in univariate analysis, and p=0.04 at multivariate logistic regression after controlling for the following variables: birth weight, gestational age, days on supplemental oxygen, systemic fungal infection, vaginal delivery). Use of erythropoietin was not significantly associated with other major sequelae of prematurity (intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis). © 2014 Elsevier Ireland Ltd. All rights reserved. CONCLUSIONS: Use of erythropoietin is an additional, independent predictor of threshold ROP in ELBW neonates. Larger prospective, population-based studies should further clarify the extent of this association.

Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial.

IMPORTANCE: NEC is a common and severe complication in premature neonates, particularly those with very-low-birth-weight (VLBW, <1500 g at birth). Probiotics including lactobacillus rhamnosus GG (LGG) proved effective in preventing NEC in preterm infants in several RCTs. OBJECTIVE: Lactoferrin, a mammalian milk glycoprotein involved in innate immune host defences, can reduce the incidence of NEC in animal models, and its action is enhanced by LGG. We tried to assess whether bovine lactoferrin (BLF), alone or with the probiotic LGG, has a similar effect in human infants, something that has not yet been studied. DESIGN: An international, multicenter, randomized, double-blind, placebo-controlled trial conducted from October 1st, 2007 through July 31st, 2010. SETTING: Thirteen Italian and New Zealand tertiary neonatal intensive care units. PARTICIPANTS: 743 VLBW neonates were assessed until discharge for development of NEC. INTERVENTION: Infants were randomly assigned to receive orally either BLF (100 mg/day) alone (group LF; n = 247) or with LGG (at 6×10(9) CFU/day; group BLF + LGG; n = 238), or placebo (Control group; n = 258) from birth until day 30 of life (45 for neonates <1000 g at birth). MAIN OUTCOME MEASURES: ≥ stage 2 NEC; death-and/or-≥ stage 2 NEC prior to discharge. RESULTS: Demographics, clinical and management characteristics of the 3 groups were similar, including type of feeding and maternal milk intakes. NEC incidence was significantly lower in groups BLF and BLF + LGG [5/247 (2.0%)] and 0/238 (0%), respectively] than in controls [14/258 (5.4%)] (RR = 0.37; 95% CI: 0.136-1.005; p = 0.055 for BLF vs. control; RR = 0.00; p < 0.001 for BLF + LGG vs. control). The incidence of death-and/or-NEC was significantly lower in both treatment groups (4.0% and 3.8% in BLF and BLF + LGG vs. 10.1% in control; RR = 0.39; 95% CI: 0.19-0.80; p = 0.008. RR = 0.37; 95% CI: 0.18-0.77; p = 0.006, respectively). No adverse effects or intolerances to treatment occurred. CONCLUSIONS AND RELEVANCE: Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of ≥ stage 2 NEC and of death-and/or ≥ stage 2 NEC in VLBW neonates. BLF might be a promising strategy to prevent NEC in NICU settings. Further data on larger sample sizes are warranted before BLF can be widespreadly used in clinical settings. TRIAL REGISTRATION: ISRCTN53107700-http://www.controlled-_trials.com/ISRCTN53107700.