Subjective versus objective, polymer bur-based selective carious tissue removal: 1-year interim analysis of a randomized clinical trial

We aimed to compare subjective (S) vs. objective (O) selective carious tissue removal using hand-excavation versus a self-limiting polymer bur, respectively. A community-based single-blind cluster-randomized controlled superiority trial was performed. This is a 1-year-interim analysis. 115 children (age 7–8 years) with ≥1 vital primary molar with a deep dentin lesion (>1/2 dentin depth) were included (60 S/55 O). The cluster was the child, with eligible molars being treated identically (91 S/86 O). Cavities were prepared and carious tissue on pulpo-proximal walls selectively removed using hand instruments (S), or a self-limiting polymer bur (Polybur P1, Komet). Cavities were restored using glass-hybrid material (Equia Forte, GC). Treatment times and children’s satisfaction were recorded. Generalized-linear models (GLM) and multi-level Cox-regression analysis were applied. Initial treatment times were not significantly different between protocols (mean; 95%CI S: 433; 404–462 sec; O: 412; 382-441 sec; p = 0.378/GLM). There was no significant difference in patients’ satisfaction (p = 0.164). No pulpal exposures occurred. 113 children were re-examined. Failures occurred in 22/84 O-molars (26.2%) and 26/90 S-molars (28.9%). Pulpal complications occurred in 5(6%) O and 2(2.2%) S molars, respectively. Risk of failure was not significantly associated with the removal protocol, age, sex, dental arch or tooth type (p > 0.05/Cox), but was nearly 5-times higher in multi-surface than single-surface restorations (HR: 4.60; 95% CI: 1.70-12.4). Within the limitations of this interim analysis, there was no significant difference in treatment time, satisfaction and risk of failure between O and S

ERAP1 promotes Hedgehog-dependent tumorigenesis by controlling USP47-mediated degradation of βTrCP.

The Hedgehog (Hh) pathway is essential for embryonic development and tissue homeostasis. Aberrant Hh signaling may occur in a wide range of human cancers, such as medulloblastoma, the most common brain malignancy in childhood. Here, we identify endoplasmic reticulum aminopeptidase 1 (ERAP1), a key regulator of innate and adaptive antitumor immune responses, as a previously unknown player in the Hh signaling pathway. We demonstrate that ERAP1 binds the deubiquitylase enzyme USP47, displaces the USP47-associated βTrCP, the substrate-receptor subunit of the SCFβTrCP ubiquitin ligase, and promotes βTrCP degradation. These events result in the modulation of Gli transcription factors, the final effectors of the Hh pathway, and the enhancement of Hh activity. Remarkably, genetic or pharmacological inhibition of ERAP1 suppresses Hh-dependent tumor growth in vitro and in vivo. Our findings unveil an unexpected role for ERAP1 in cancer and indicate ERAP1 as a promising therapeutic target for Hh-driven tumors

A potential link among antioxidant enzymes, histopathology, and trace elements in canine visceral leishmaniasis.

Canine visceral leishmaniasis (CVL) is a severe and fatal systemic chronic inflammatory disease. We investigated the alterations in, and potential associations among, antioxidant enzymes, trace elements and histopathology in CVL. Blood and tissue levels of Cu-Zn superoxide dismutase, catalase and glutathione peroxidase were measured in mixed-breed dogs naturally infected with Leishmania infantum chagasi, symptomatic (n = 19) and asymptomatic (n = 11). Serum levels of copper, iron, zinc, selenium and nitric oxide, and plasma lipid peroxidation were measured. Histological and morphometric analyses were conducted of lesions in liver, spleen and lymph nodes. We found lower blood catalase and glutathione peroxidase activity to be correlated with lower iron and selenium respectively. However, higher activity of Cu- Zn superoxide dismutase was not correlated with the increase in copper and decreased in zinc observed in infected animals compared to controls. Organ tissue was characterized by lower enzyme activity in infected dogs than in controls, but this was not correlated with trace elements. Lipid peroxidation was higher in symptomatic than in asymptomatic and control dogs and was associated with lesions such as chronic inflammatory reaction, congestion, haemosiderin and fibrosis. Systemic iron deposition was observed primarily in the symptomatic dogs showing a higher tissue parasite load. Dogs with symptomatic CVL displayed enhanced LPO and Fe tissue deposition associated with decreased levels of antioxidant enzymes. These results showed new points in the pathology of CVL and might open new treatment perspectives associated with antioxidants and the role of iron in the pathogenesis of CVL

Age of onset and cumulative risk of mental disorders:a cross-national analysis of population surveys from 29 countries

Background: Information on the frequency and timing of mental disorder onsets across the lifespan is of fundamental importance for public health planning. Broad, cross-national estimates of this information from coordinated general population surveys were last updated in 2007. We aimed to provide updated and improved estimates of age-of-onset distributions, lifetime prevalence, and morbid risk. Methods: In this cross-national analysis, we analysed data from respondents aged 18 years or older to the World Mental Health surveys, a coordinated series of cross-sectional, face-to-face community epidemiological surveys administered between 2001 and 2022. In the surveys, the WHO Composite International Diagnostic Interview, a fully structured psychiatric diagnostic interview, was used to assess age of onset, lifetime prevalence, and morbid risk of 13 DSM-IV mental disorders until age 75 years across surveys by sex. We did not assess ethnicity. The surveys were geographically clustered and weighted to adjust for selection probability, and standard errors of incidence rates and cumulative incidence curves were calculated using the jackknife repeated replications simulation method, taking weighting and geographical clustering of data into account. Findings: We included 156 331 respondents from 32 surveys in 29 countries, including 12 low-income and middle-income countries and 17 high-income countries, and including 85 308 (54·5%) female respondents and 71 023 (45·4%) male respondents. The lifetime prevalence of any mental disorder was 28·6% (95% CI 27·9–29·2) for male respondents and 29·8% (29·2–30·3) for female respondents. Morbid risk of any mental disorder by age 75 years was 46·4% (44·9–47·8) for male respondents and 53·1% (51·9–54·3) for female respondents. Conditional probabilities of first onset peaked at approximately age 15 years, with a median age of onset of 19 years (IQR 14–32) for male respondents and 20 years (12–36) for female respondents. The two most prevalent disorders were alcohol use disorder and major depressive disorder for male respondents and major depressive disorder and specific phobia for female respondents. Interpretation: By age 75 years, approximately half the population can expect to develop one or more of the 13 mental disorders considered in this Article. These disorders typically first emerge in childhood, adolescence, or young adulthood. Services should have the capacity to detect and treat common mental disorders promptly and to optimise care that suits people at these crucial parts of the life course. Funding: None.</p

Anales del III Congreso Internacional de Vivienda y Ciudad "Debate en torno a la nueva agenda urbana"

Acta de congresoEl III Congreso Internacional de Vivienda y Ciudad “Debates en torno a la NUEVa Agenda Urbana”, ha sido una apuesta de alto compromiso por acercar los debates centrales y urgentes que tensionan el pleno ejercicio del derecho a la ciudad. Para ello las instituciones organizadoras (INVIHAB –Instituto de Investigación de Vivienda y Hábitat y MGyDH-Maestría en Gestión y Desarrollo Habitacional-1), hemos convidado un espacio que se concretó con potencia en un debate transdisciplinario. Convocó a intelectuales de prestigio internacional, investigadores, académicos y gestores estatales, y en una metodología de innovación articuló las voces académicas con las de las organizaciones sociales y/o barriales en el Foro de las Organizaciones Sociales que tuvo su espacio propio para dar voz a quienes están trabajando en los desafíos para garantizar los derechos a la vivienda y los bienes urbanos en nuestras ciudades del Siglo XXI

Análise quantitativa de movimentos oculares em pacientes MJD

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de MedicinaSpinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph’s disease (MJD), is the most worldwide known SCA. MJD is characterized by progressive deterioration of cerebellar, pyramidal, extrapyramidal, motor neuron and ocular motor systems. Ocular motor manifestations constitute early findings in the disease process. The main goal of this work was to describe and analyze eye movement abnormalities in a large cohort of MJD patients. We studied 38 MJD patients (24 females) and 22 controls (12 females). All participants underwent detailed video-oculographic analysis, including eccentric gaze, smooth pursuit, saccades, optokinetic response (OKR) and vestibulo-ocular reflex (VOR). Ocular motor data in MJD patients was compared with that of controls and further correlated with motor disability using Scale for the Assessment and Rating of Ataxia (SARA), disease duration and number of CAG repeats.MJD patients showed lower smooth pursuit, OKR and VOR gain than controls. Saccade velocity was significantly higher in patients. SARA score positively correlated with intensity of eccentric nystagmus and negatively correlated with VOR and OKR gain. Number of CAG repeats negatively correlated with VOR and OKR gain. Disease duration negatively correlated with OKR gain.We show in a large sample of MJD patients that OKR, VOR and pursuit gain, together with saccade velocity are strong markers of disease, genetic status and progression in MJD. .A ataxia espinhocerebelosa tipo 3 (SCA3), também conhecida como doença Machado-Joseph (MJD), é a SCA mais comum mundialmente. MJD é caracterizada por uma deterioração progressiva dos circuitos cerebelosos, piramidais e extrapiramidais. As manifestações oculomotoras nesta doença são frequentes e aparecem precocemente.  O objetivo principal deste trabalho foi descrever e analisar as alterações oculomotores de uma grande coorte de doentes MJD. Estudámos 38 pacientes MJD (24 mulheres) e 22 controlos (12 mulheres). Todos os participantes realizaram uma video-oculografia na qual foram analisados os movimentos oculares, incluindo fixação, excentricidade, perseguição, sacadas, resposta optocinética (OKR) e reflexo vestíbulo-ocular (VOR). Os dados oculomotores dos doentes MJD foram comparados com os dos controlos e posteriormente correlacionados com a incapacidade motora, medida pela Scale for the Assessment and Rating of Ataxia (SARA), duração da doença e repetições CAG.  Os doentes MJD mostraram diminuição da perseguição, da OKR e do ganho do VOR em relação aos controlos. A velocidade das sacadas foi significativamente maior nos doentes. O score SARA correlacionou-se positivamente com a intensidade do nistagmo excêntrico e negativamente com o ganho do VOR e OKR. A duração da doença correlacionou-se negativamente com o ganho de OKR.  Mostrámos, assim, numa grande coorte de doentes MJD que as alterações do OKR, VOR e perseguição, juntamente com a velocidade das sacadas são bons marcadores de doença, status genético e progressão na MJD.

Groupon e il couponing: un\u2019analisi sulla soddisfazione e sulla fedelt\ue0 dei merchant

Il boom dei siti di social couponing, trainati dal leader Groupon, \ue8 uno dei fenomeni caratterizzanti l\u2019e-commerce a livello mondiale degli ultimi 3-5 anni. I pochi studi disponibili sull\u2019argomento prendono in considerazione prevalentemente gli impatti di tale fenomeno sugli acquirenti finali, che possono accedere a servizi a prezzi particolarmente scontati. Dall\u2019altro lato, nella prospettiva dei c.d. merchant, cio\ue8 delle imprese \u201cinserzioniste\u201d, i siti di couponing rappresentano un nuovo strumento di marketing e anche la prima concreta possibilit\ue0 di accesso all\u2019e-commerce per molte imprese di micro-piccole dimensioni. Il presente lavoro esamina il social couponing da questa seconda prospettiva, quella dei merchant, esplorando i driver della loro soddisfazione e della loro fedelt\ue0 al sito di couponing. Attraverso una ricerca su un campione di 121 merchant italiani che hanno pubblicato offerte su Groupon, si evidenzia un forte legame tra soddisfazione (complessiva e rispetto a cinque diverse motivazioni di utilizzo del sito) e fedelt\ue0. I risultati evidenziano, inoltre, come tra i merchant meno fedeli emerga un quadro confuso degli obiettivi perseguibili attraverso il couponing

Does Social Couponing Stimulate Positive E-Word-of-Mouth and Referrals?

In the last years an increasing number of hotels have decided to run social coupon campaigns through Groupon and other daily deal sites. Available evidence suggests that several hotel managers have overlooked the \u201csocial\u201d component of social couponing. In fact they have mainly considered the short-term effects (i.e. increased sales) of this marketing tool, underestimating its potential benefits in terms of e-word-of mouth (eWOM) and referrals. The aim of this study is therefore to shed light on the potential of social couponing to stimulate positive eWOM and referrals. For this purpose, the paper presents the results of a content analysis of 564 TripAdvisor reviews posted by guests that have stayed at 76 Italian hotels using a Groupon\u2019s coupon. In addition, this study identifies the most important coupon-related factors which are able to explain the positive vs. negative eWOM. Beyond enriching theoretical knowledge on social couponing, this paper highlights that the decision of guests to engage in either positive or negative eWOM about the hotel is influenced by some coupon-related factors which can be managed by the hotels

The perceived effectiveness of social couponing campaigns for hotels in Italy

Purpose\u2013 The purpose of this paper is to analyze the effectiveness of social couponing campaigns for hotels. In particular, the perceived effectiveness related to four specific objectives is explored (acquiring and retaining new customers, building brand awareness, balancing seasonality and stimulating demand among existing customers).Design/methodology/approach\u2013 A questionnaire-based survey was conducted that involved 108 hotels, each of which has run at least one social couponing campaign through Groupon in Italy. The importance-performance approach was applied to analyze the data.Findings\u2013 Overall, the perceived effectiveness of social couponing for hotels is quite low. Social couponing is useful to increase brand awareness but does not encourage customer behavioral loyalty. Larger hotels can successfully use this marketing tool to balance demand seasonality.Research limitations/implications\u2013 The sample size is limited but includes approximately one-fourth of all Italian hotels that have run social coupon campaigns through Groupon. Only social couponing campaigns run through one daily deal site (Groupon) in one country (Italy) were considered.Practical implications\u2013 Social couponing is not perceived as equally effective for all hotels. This study provides hotel managers with suggestions for deciding whether to allocate a share of their marketing resources to social couponing.Originality/value\u2013 To the authors\u2019 knowledge, this is the first paper to present field data to complement the available theoretical knowledge on social couponing for hotels