Evidence for a pathogenic role of extrafollicular, IL-10-producing CCR6+B helper T cells in systemic lupus erythematosus.

Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4+CCR6+IL-7R+T cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6+B helper T cells were phenotypically distinct from follicular helper T (TFH) cells and lacked BCL6 expression. In peripheral blood, a CCR6+T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation-associated surface markers. CD4+CCR6+T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4+CCR6+IL-7R+T cells were associated with the presence of pathogenic anti-dsDNA (double-stranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10-producing CCR6+T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.

Membrane human equilibrative nucleoside transporter 1 is associated with a high proliferation rate and worse survival in resected intrahepatic cholangiocarcinoma patients not receiving adjuvant treatments.

Human equilibrative nucleoside transporter 1 (hENT-1) is a membrane nucleoside transporter mediating the intracellular uptake of nucleosides and their analogues. hENT-1 was recently reported to have a predictive role in intrahepatic cholangiocarcinoma (iCC) patients receiving adjuvant gemcitabine-based chemotherapy, but its biological and clinical significance in iCC remains unsettled. This study investigated the role of hENT-1 in regulating tumour growth and predicting the survival of 40 resected iCC patients not receiving adjuvant treatments. hENT-1 expression was found to be significantly higher in iCC than in the matched non-tumoural liver. Patients harbouring hENT-1 localised on the tumour cell membrane had a worse overall survival than membrane hENT-1-negative patients (median 21.2 months vs 30.3 months, p = 0.031), with an adjusted hazard ratio of 2.8 (95% confidence interval 1.01-7.76). Moreover, membrane hENT-1-positive patients had a higher percentage of Ki67-positive cells in tumour tissue than membrane hENT-1-negative patients (median 23% vs 5%, p < 0.0001). Functional analyses in iCC cell lines revealed that hENT-1 silencing inhibited cell proliferation and induced apoptosis in HUH-28 cells expressing hENT-1 on the cell membrane, but not in SNU-1079 cells expressing the transporter only in the cytoplasm. Overall, these findings suggest that membrane hENT-1 is involved in iCC proliferation and associated with worse survival in resected iCC patients. Further prospective studies on larger cohorts are required to confirm these results and better define the potential prognostic role of membrane hENT-1 in this setting of patients.

Repression of miR-31 by BCL6 stabilizes the helper function of human follicular helper T cells.

Follicular helper T cells (TFHs) are a key component of adaptive immune responses as they help antibody production by B cells. Differentiation and function of TFH cells are controlled by the master gene BCL6, but it is largely unclear how this transcription repressor specifies the TFH program. Here we asked whether BCL6 controlled helper function through down-regulation of specific microRNAs (miRNAs). We first assessed miRNA expression in TFH cells and defined a TFH-specific miRNA signature. We report that hsa-miR-31-5p (miR-31) is down-regulated in TFH; we showed that BCL6 suppresses miR-31 expression by binding to its promoter; and we demonstrated that miR-31 inhibits the expression of molecules that control T-helper function, such as CD40L and SAP. These findings identify a BCL6-initiated inhibitory circuit that stabilizes the follicular helper T cell program at least in part through the control of miRNA transcription. Although BCL6 controls TFH activity in human and mouse, the role of miR-31 is restricted to human TFH cell differentiation, reflecting a species specificity of the miR-31 action. Our findings highlight miR-31 as a possible target to modulate human T cell dependent antibody responses in the settings of infection, vaccination, or immune dysregulation.

Multiple stab wounds: understanding the manner of death through the psychological autopsy.

A 48-year-old physical therapist with no history of psychiatric disorders or suicidal tendencies was found dead by his relatives inside his apartment. Multiple stab wounds were present on the chest and the abdomen. Several more superficial cuts were also seen on the neck and the left wrist. At the death scene, there was a large pool of blood in the room, with secondary droplets and stains; a kitchen knife was found beside the body, and a suicide note on a table. Especially the number of wounds raised strong suspicion of a homicide in the first instance but some circumstances (the farewell letter, the absence of clothing injuries, no signs of third-party involvement) and autopsy findings (absence of defense or blunt injuries, the localization of the wounds, the presence of hesitation marks) pointed toward a suicide etiology. Because of the many stab injuries and the lack of a psychiatric history, further forensic investigations were required including a so-called psychological autopsy. This case report highlights that only a comprehensive interpretation of all the elements (circumstances, the scene of death, autopsy findings, and psychological autopsy) can lead to the correct solution of atypical cases of suicide.

Antiviral activity of hemolymph of Podalia against rubella virus.

Many active principles produced by animals, plants and microorganisms have been employed in the development of new drugs for the treatment of human diseases. Among animals known to produce pharmacologically active molecules that interfere in human cell physiology. Rubella virus (genus Rubivirus, family Togaviridae) is a single stranded RNA virus of positive genome polarity. Rubella virus infection of susceptible women during the first trimester of pregnancy often results in long-term virus persistence in the fetus causing multiple organ abnormalities. Potent antiviral activity against rubella virus (RV) has been observed in the hemolymph of Podalia sp. (Lepidoptera: Megalopygidae). This study evaluated the effect of hemolymph on RV infected Statens Serum Institute Rabbit Cornea (SIRC) cells. Results of cell viability and cell proliferation assays indicated that hemolymph was not toxic to cultured SIRC cells. Viral binding assay, antiviral assay, PCR, real-time PCR, and transmission electron microscopy were used to demonstrate that hemolymph in post-treatment could inhibit the production of infectious RV particles. Specifically, hemolymph was found to inhibit RV adsorption to the SIRC cells.

Antiviral activity of hemolymph of Podalia against rubella virus

Many active principles produced by animals, plants and microorganisms have been employed in the development of new drugs for the treatment of human diseases. Among animals known to produce pharmacologically active molecules that interfere in human cell physiology. Rubella virus (genus Rubivirus, family Togaviridae) is a single stranded RNA virus of positive genome polarity. Rubella virus infection of susceptible women during the first trimester of pregnancy often results in long-term virus persistence in the fetus causing multiple organ abnormalities. Potent antiviral activity against rubella virus (RV) has been observed in the hemolymph of Podalia sp. (Lepidoptera: Megalopygidae). This study evaluated the effect of hemolymph on RV infected Statens Serum Institute Rabbit Cornea (SIRC) cells. Results of cell viability and cell proliferation assays indicated that hemolymph was not toxic to cultured SIRC cells. Viral binding assay, antiviral assay, PCR, real-time PCR, and transmission electron microscopy were used to demonstrate that hemolymph in post-treatment could inhibit the production of infectious RV particles. Specifically, hemolymph was found to inhibit RV adsorption to the SIRC cells.

Antiviral action of hydromethanolic extract of geopropolis from scaptotrigona postica against antiherpes simplex virus (HSV-1)

The studies on chemical composition and biological activity of propolis had focused mainly on species Apis mellifera L. (Hymenoptera: Apidae). There are few studies about the uncommon propolis collected by stingless bees of the Meliponini tribe known as geopropolis. The geopropolis from Scaptotrigona postica was collected in the region of Barra do Corda, Maranhão state, Brazil. The chemical analysis of hydromethanolic extract of this geopropolis (HMG) was carried out through HPLC-DAD-ESI-MS/MS and the main constituents found were pyrrolizidine alkaloids and C-glycosyl flavones. The presence of alkaloids in extracts of propolis is detected for the first time in this sample. The antiviral activity of HMG was evaluated through viral DNA quantification experiments and electron microscopy experiments. Quantification of viral DNA from herpes virus showed reduction of about 98% in all conditions and concentration tested of the HMG extract. The results obtained were corroborated by transmission electron microscopy, in which the images did not show particle or viral replication complex. The antiviral activity of C-glycosyl flavones was reported for a variety of viruses, being observed at different points in the viral replication. This work is the first report about the antiviral activity of geopropolis from Scaptotrigona postica, in vitro, against antiherpes simplex virus (HSV).

Study for the quality assessment of abstracts presented to Italian public health national conferences: a six years survey.

BACKGROUND: Oral and poster presentations at congresses are essential to spread scientific knowledge among the medical community. Many scientific societies have analyzed the quality of papers presented at their meetings but no information on abstracts' evaluation has been presented in Public Health field. DESIGN AND METHODS: This study aims to examine the quality of abstracts presented at annual meetings of Italian Public Health Society (SItI) in the period 2005-2010 through a validated checklist grid, evaluating eight dimensions: Inherency, Structure, Originality, Objectives, Study design, Sources, Results, Conclusions. Each item was scored from 0 to 3 points (max score: 24) and we used the average score in our study (15) as threshold of good quality. A multivariate analysis was performed in order to investigate predictors of score of abstracts presented. RESULTS: A total of 4,399 abstracts (1,172 oral communications, 3,227 posters) was examined. Around 60% were submitted by Universities and around 40% were from Central Italy. The highest quality was found in the fields of Vaccines (average score 18.9), Infectious Diseases (18) and in abstracts submitted by Universities (16.4). Predictors of lower quality identified were geographical area and affiliation (p= 0.002). Abstracts containing well-written Results, Conclusions and Objectives (3 points) were more likely to be of high quality(OR=55.6, OR=41.9, and OR=157.4; p>0.001) CONCLUSIONS: This is the first European study evaluating the quality of abstracts in the public health field. A reliable evaluation tool is fundamental to offer a transparent methodology of assessment and to improve the quality of research.

Epidemiological and molecular characterization of rubella virus isolated in São Paulo, Brazil during 1997-2004.

Rubella virus (RV) infection during the early stages of pregnancy can lead to serious birth defects, known as the congenital rubella syndrome (CRS). In 2003, the Pan American Health Organization (PAHO) adopted a resolution calling for the elimination of rubella and the congenital rubella syndrome (CRS) in the Americas by the year 2010. Brazil will have implemented the recommended PAHO strategy for elimination and interruption of endemic rubella virus transmission. The characterization of genotypes during the final stages of rubella elimination is important for determining whether new rubella isolates represent endemic transmission or importations. Samples (blood, urine, cerebrospinal fluid, and throat swabs) collected from patients with symptoms suggestive of rubella infection in 1997-2004 were isolated in cell culture and genotyped. Twenty-eight sequences were analyzed and two genotypes were identified: 1a and 1G. The information reported in this paper will contribute to understanding the molecular epidemiology of RV in São Paulo, Brazil.

Phylogenetic analysis of rubella virus strains during an outbreak in São Paulo, 2007-2008.

Rubella virus (RV) is an important human pathogen that causes rubella, an acute contagious disease. It also causes severe birth defects collectively known as congenital rubella syndrome when infection occurs during the first trimester of pregnancy. Here, we present the phylogenetic analysis of RV that circulated in São Paulo during the 2007-2008 outbreak. Samples collected from patients diagnosed with rubella were isolated in cell culture and sequenced. RV RNA was obtained from samples or RV-infected cell cultures and amplified by reverse transcriptase-polymerase chain reaction. Sequences were assigned to genotypes by phylogenetic analysis using RV reference sequences. Seventeen sequences were analyzed, and three genotypes were identified: 1a, 1G, and 2B. Genotypes 1a and 1G, which were isolated in 2007, were responsible for sporadic rubella cases in São Paulo. Thereafter, in late 2007, the epidemiological conditions changed, resulting in a large RV outbreak with the clear dominance of genotype 2B. The results of this study provide new approaches for monitoring the progress of elimination of rubella from São Paulo, Brazil.

Incidence rates of surgically treated idiopathic carpal tunnel syndrome in blue- and white-collar workers and housewives in Tuscany, Italy.

OBJECTIVES: Rates of surgically treated carpal tunnel syndrome (CTS) among blue- and white-collar workers and housewives in the general population were compared. METHODS: Surgically treated cases of idiopathic CTS were investigated among 25-59-year-old residents of Tuscany, Italy, during 1997-2000, based on obligatory discharge records from all Italian public/private hospitals, archived according to residence on Tuscany's regional database. Population data were extracted from the 2001 census. RESULTS: After excluding repeat admissions, 8801 eligible cases were identified. Age-standardised rates (per 100 000 person-years) of surgical CTS were: "blue-collar women", 367.8; "white-collar women", 88.1; "housewives", 334.5; "blue-collar men", 73.5; and "white-collar men", 15.3. Compared with reference categories (same-sex white-collar workers): female blue-collar workers experienced a 4.2-fold higher standardised rate; housewives, a 3.8-fold excess; and male blue-collar workers, a 4.8-fold excess (all p<0.001). Male and female blue-collar workers showed approximately three to sevenfold higher age-specific rates compared to their white-collar counterparts (all p<0.001). Housewives' rates were similar to those of blue-collar female workers up to 40-44 years of age, after which they were significantly lower (p<0.002). At all ages, housewives' rates were much higher (p<0.001) than those of white-collar women. CONCLUSIONS: Surgically treated CTS was three to seven times more common (depending on age/gender) in blue-collar than in white-collar workers, which is difficult to explain by differences in body weight or other individual factors. Thus, occupational risk factors seem relevant throughout working life. The high rates for full-time housewives suggest that domestic chores should be investigated as a possible risk factor for CTS.

Isolation and genotype analysis of rubella virus from a case of Guillain-Barré syndrome.

Rubella virus (RV) infection has sporadically been linked to Guillain-Barré syndrome (GBS), but the association with RV has been based only on clinical and/or serological backgrounds. In the present case it was possible to isolate RV (genotype 1a) from cerebrospinal fluid and peripheral blood mononuclear cells of an 18-year-old woman diagnosed with GBS after clinical manifestations of rubella. This report contributes to confirm RV as one of the triggering pathogens of this peripheral nervous system disease.

Evaluation of an occupational therapy program for patients with spinal cord injury.

STUDY DESIGN: Clinical controlled trial. OBJECTIVES: To evaluate the effectiveness of an occupational therapy (OT) program combined with neuromotor rehabilitation, by assessing the degree of functional independence reached by patients with spinal cord injuries at first hospitalization. SETTINGS: Subjects selected from the Spinal Cord Unit of the Rehabilitation Institute of Montecatone (Imola, Italy). PARTICIPANTS: Thirty-six male patients below age 60, with complete paraplegia (ASIA-A) in thoracic-lumbar level, at first hospitalization. METHODS: Patients were divided into experimental and control groups. Subjects in the experimental group underwent neuromotor rehabilitation coupled with an OT program, whereas those in the control group followed neuromotor rehabilitation only. Increase in functional independence at discharge was evaluated by the Valutazione Funzionale Mielolesi (VFM) assessment scale. RESULTS: Patients in the experimental group showed a significant increase in the total VFM score, and in domains concerning transfers and wheelchair use. A significant improvement was observed in unmarried patients as compared to married ones. CONCLUSION: An OT service within a Spinal Cord Unit allows us to achieve a higher level of functional independence.

[Usefulness of surface electromyography of hand muscles in the assessment of myoelectric parameters changes due to repetitive manual tasks]. / Applicazione dell'elettromiografia di superficie dei muscoli della mano nello studio delle patologie da sovraccarico biomeccanico.

The aim of this project was to investigate the possible role of sEMG in the diagnosis of Carpal tunnel syndrome (CTS). The study group consisted of 37 subjects, of whom 14 (control group) were not employed in manual tasks and 23 (exposed) were engaged in repetitive and forceful manual tasks. Of the 23 exposed workers, 10 reported CTS symptoms, whereas all the subjects of the control group resulted asymptomatic. The surface electromyography signal was recorded from the abductor pollicis brevis muscle, using different levels of isometric contraction: 20% and 50% of the maximum voluntary contraction (MVC), respectively. The initial values and rate of change of the average rectified value (ARV), mean power spectral frequency (MNF) and conduction velocity (CV) were calculated. Moreover the study protocol included clinical evaluation and electrodiagnostic study of the median nerve. Data from the exposed and control group were compared. Statistically significant differences between the two groups were found for ARV initial value and for CV and MNF rate of change at 50% MVC. These parameters resulted lower in the exposed group, with the lowest values among symptomatic subjects. Possible explanations may be the loss of motor units, particularly affecting the fast and fatigable type II muscle fibers, involved in the myoelectric manifestation of fatigue. In conclusion, this technique was able to show different myoelectric patterns and manifestations of fatigue between subjects exposed and nonexposed to manual intensive work, suffering or not suffering from CTS.

Analysis of behavior-related excitatory inputs to a central pacemaker nucleus in a weakly electric fish.

Gymnotid electric fish explore their environment and communicate with conspecifics by means of rhythmic electric organ discharges. The neural command for each electric organ discharge arises from activity of a medullary pacemaker nucleus composed of two neuronal types: pacemaker and relay cells. During different behaviors as in courtship, exploration and agonistic interactions, these species display specific electric organ discharge frequency and/or waveform modulations. The neural bases of these modulations have been explained in terms of segregation of inputs to pacemaker or relay cells, as well as differential activation of the glutamate receptors of these cells. One of the most conspicuous electric organ discharge frequency modulations in Gymnotus carapo results from the activation of Mauthner cells, a pair of reticulospinal neurons that are involved in the organization of sensory-evoked escape responses in teleost fish. The activation of Mauthner cells in these animals produces a prolonged increase in electric organ discharge rate, whose neural mechanisms involves the activation of both N-methyl-D-aspartate (NMDA) and metabotropic glutamatergic receptors of pacemaker cells. Here we provide evidence which indicates that pacemaker cells are the only cellular target of the synaptic inputs responsible for the Mauthner cell initiated electric organ discharge modulation at the medullary pacemaker nucleus. Additionally, although pacemaker cells express both NMDA and non-NMDA ionotropic receptors, we found that non-NMDA receptors are not involved in this synaptic action which suggests that NMDA and non-NMDA receptor subtypes are not co-localized at the subsynaptic membrane. NMDA receptor activation of pacemaker cells seems to be an efficient neural strategy to produce long-lasting enhancements of the fish sampling capability during Mauthner cell-initiated motor behaviors.

Prevention of work related eye injuries: long term assessment of the effectiveness of a multicomponent intervention among metal workers.

BACKGROUND: Systematic assessments of the effectiveness of interventions to prevent work related eye injuries are needed. AIM: To investigate the long term effectiveness of a multicomponent prevention campaign. METHODS: The campaign (conducted in collaboration with the local Employers' Association and Trade Unions) targeted all 237 metal-ware factories in the district of Imola, Italy. Based on preliminary inspections, the main intervention included distribution to all factories of specific educational brochures and broadcasting/publication of television/radio programmes and local newspaper articles containing expert advice on the subject. This was followed by a four year "post-intervention reinforcement" period of unannounced official inspections. Main outcome measures analysed were eye injury rates (versus non-eye injury rates) among metal workers during "pre-intervention" (1988-90), "peri-intervention" (1991-92), "post-intervention reinforcement" (1993-96), "late post-intervention" (1997-2000), and "very late post-intervention" (2001-03) periods with respect to two comparison sectors (construction and wood/ceramics). RESULTS: A Poisson regression in which the eye injury rates were modelled for each sector, period, and interaction, adjusting for non-eye injury rates, was chosen. The periods did not by themselves determine an overall reduction in eye injuries. The period/sector interaction terms were related to significant reductions for the metal sector when crossed with the "post-intervention reinforcement" (IRR = 0.77, 95% CI 0.61 to 0.97; % decline = 23.4), the "late post-intervention" (IRR = 0.63, 95% CI 0.50 to 0.79; % decline = 37.4), and the "very late post-intervention" (IRR = 0.58, 95% CI 0.43 to 0.77; % decline = 42.4) periods, suggesting a sustained reduction in eye injury risk following the main intervention. CONCLUSION: Results suggest that a carefully coordinated, extensive, multicomponent intervention can lead to lasting reductions in the burden of eye injuries.

Molecular analysis of a Measles virus isolate from Brazil: a case originating in Japan.

This study reports on molecular analysis of a Measles virus (MV) isolate from a patient who was infected in Japan but showed symptoms after arriving to Brazil. This patient had typical clinical measles infection symptoms: fever, rash, cough and coryza. After isolating the virus in B95a cells, a fragment of the nucleoprotein (N) gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and subjected to direct nucleotide sequencing. The sequence data showed that the MV isolate of concern is of the D5 genotype.

[Central modulation of a sensory system by a motor command. One intention with two results]. / Modulación central de un sistema sensorial por un comando motor. Una intención con dos resultados.

INTRODUCTION AND DEVELOPMENT: Neuronal mechanisms that underlie diverse sensory motor integration processes (SMI) are essential for the motor control and determine the general organization of the nervous system. Spinal cord, sensory relay nucleus of brainstem and thalamus as well as higher motor control structures are some of the levels, of increasing complexity, at which several processes of SMI occurs during the execution of a motor act. The mechanisms that underlie SMI strategies operating at higher hierarchical levels of motor control are poorly understood. Escape response in teleosts fish is an advantageous experimental model for the analysis of the neural basis of behavior and of the mechanisms and functional consequences of diverse strategies of ISM. We describe several levels of ISM that operate in the neural system that organize this response in most teleosts and we deal with a detailed description of a novel strategy that occurs in Gymnotus carapo, a South American weakly electric fish. In this species, the activation of the Mauthner cell, a command neuron for the initial phase of escape, produces a powerful modulation of the sensory system responsible for active electrorreception, its main sensory modality. CONCLUSION: The neural basis of behavior, even those relatively simple, exhibit several strategies of complex SMI that determine its performance and whose cellular mechanisms begin to be unraveled.