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La ascariasis es una enfermedad parasitaria que diezma la salud de cientos de miles de seres humanos, especialmente en los países en desarrollo. Sin embargo, la falta de profilaxis adecuada del parásito, asociado con un mayor riesgo de sufrir enfermedades inmunes, es un problema principalmente en los países desarrollados donde la prevalencia del parásito es muy baja. La relación evolutiva y los mecanismos por los cuales el parásito fue capaz de colonizar y establecerse en el huésped humano aún no se han descifrado. Del mismo modo, los mecanismos inmunes (proximales) de respuesta del huésped para eliminar o controlar el parásito no se entienden completamente. La comprensión de estos mecanismos nos permitirá establecer mejores tratamientos médicos, evitando efectos indeseables y más enfocados en el control de la parasitosis, así como para la terapia de estas enfermedades inmunológicas asociadas con la relación huésped-ascárido. Ascariasis is a debilitating parasitic disease that has decimated the health of hundreds of thousands of human beings, especially in developing countries. The lack of adequate prophylaxis of the parasite associated with an increased risk of immunological disease is a challenge mainly in developed countries where the prevalence of this parasite is very low. The evolutionary relationship and mechanisms by which the parasite was able to colonize and establish itself in human hosts have not yet been unraveled. In addition, the host immune response mechanisms to eliminate or control the parasite are not fully understood. Understanding these immunological mechanisms (proximates) will allow establishing better medical treatments for diseases related to the positive effects of parasitosis, thus also avoiding the undesirable effects of the parasitosis itself. A ascaridíase é uma doença parasitária que dizima a saúde de milhares de seres humanos, principalmente nos países em desenvolvimento. No entanto, a falta de profilaxia adequada do parasito, associada ao aumento do risco de doenças imunológicas, é um problema principalmente em países desenvolvidos onde a prevalência do parasito é muito baixa. A relação evolutiva e os mecanismos pelos quais o parasito foi capaz de colonizar e se estabelecer no hospedeiro humano ainda não tem sido decifrados. Da mesma forma, os mecanismos de resposta imune do hospedeiro para eliminar ou controlar o parasito não são totalmente compreendidos. A compreensão desses mecanismos permitirá estabelecer melhores tratamentos médicos, evitando efeitos indesejáveis e mais voltados para o controle das parasitoses, bem como para a terapia dessas doenças imunológicas associadas à relação hospedeiro-ascarídeo.

Context A frame score prediction equation developed specifically for Nellore cattle could be an auxiliary tool to improve mating decisions on the basis of feed resources and production-system objectives. Aims Estimate genetic parameters for frame by using a prediction equation developed for Nellore cattle and genetic associations between frame score (FRAME) and growth-, reproductive-, carcass- and feed efficiency-related traits, and five bioeconomic indexes. Methods Birth weight (BW), adjusted weight at 120 (W120), 210 (W210) and 450 (W450) days of age, adult weight (AW), age at first calving (AFC), probability of precocious calving (PPC30), stayability (STAY), accumulated cow productivity (ACP), adjusted scrotal circumference at 365 (SC365) and 450 (SC450) days of age, rib eye area (REA), subcutaneous backfat thickness (BFT), rump fat thickness (RFT), intramuscular fat percentage (IMF), residual feed intake (RFI) and dry-matter intake (DMI) were included in the analyses. Frame score was calculated using the multiple linear regression (MLR) prediction method. The estimation of genetic parameters was performed using a linear animal model, except for PPC30 and STAY, which were estimated through a threshold animal model. The correlated response in FRAME considering selection for growth-, reproductive-, carcass- and feed efficiency-indicator traits were obtained in the context of single-trait selection and a multiple-trait context. Key results Heritability estimated for FRAME was moderate (0.30 ± 0.09). Frame score showed moderate genetic correlations with growth traits, BW (0.51 ± 0.08), W120 (0.41 ± 0.07), W210 (0.35 ± 0.07) and W450 (0.29 ± 0.08). The genetic correlation estimates between FRAME and RFT was high (−0.84 ± 0.02), but low with ACP (0.25 ± 0.08) and RFI (0.10 ± 0.13). In the single-trait and multi-trait contexts, there was a lower correlated gain for FRAME when the selection was applied for traits commonly measured in beef cattle breeding programs. Conclusion Selection to increase growth traits would lead to an increase in frame size and herd nutritional requirements, and it would reduce the carcass fatness level and early heifer sexual precocity. FRAME could be an alternative trait to monitor calf birth weight. Implications Selection for FRAME is feasible, and the most suitable frame score value depends on the production system objectives and feed resources.

Humans perceive light in the visible spectrum (400-700 nm). Some night vision systems use infrared light that is not perceptible to humans and the images rendered are transposed to a digital display presenting a monochromatic image in the visible spectrum. We sought to develop an imaging algorithm powered by optimized deep learning architectures whereby infrared spectral illumination of a scene could be used to predict a visible spectrum rendering of the scene as if it were perceived by a human with visible spectrum light. This would make it possible to digitally render a visible spectrum scene to humans when they are otherwise in complete “darkness” and only illuminated with infrared light. To achieve this goal, we used a monochromatic camera sensitive to visible and near infrared light to acquire an image dataset of printed images of faces under multispectral illumination spanning standard visible red (604 nm), green (529 nm) and blue (447 nm) as well as infrared wavelengths (718, 777, and 807 nm). We then optimized a convolutional neural network with a U-Net-like architecture to predict visible spectrum images from only near-infrared images. This study serves as a first step towards predicting human visible spectrum scenes from imperceptible near-infrared illumination. Further work can profoundly contribute to a variety of applications including night vision and studies of biological samples sensitive to visible light.

Rationale: Mechanical ventilation is a mainstay of intensive care but contributes to the mortality of patients through ventilator induced lung injury. Extracellular Cyclophilin A is an emerging inflammatory mediator and metalloproteinase inducer, and the gene responsible for its expression has recently been linked to COVID-19 infection. Objectives: Here we explore the involvement of extracellular Cyclophilin A in the pathophysiology of ventilator-induced lung injury. Methods: Mice were ventilated with low or high tidal volume for up to 3 hours, with or without blockade of extracellular Cyclophilin A signalling, and lung injury and inflammation were evaluated. Human primary alveolar epithelial cells were exposed to in vitro stretch to explore the cellular source of extracellular Cyclophilin A, and Cyclophilin A levels were measured in bronchoalveolar lavage fluid from acute respiratory distress syndrome patients, to evaluate clinical relevance. Measurements and Main Results: High tidal volume ventilation in mice provoked a rapid increase in soluble Cyclophilin A levels in the alveolar space, but not plasma. In vivo ventilation and in vitro stretch experiments indicated alveolar epithelium as the likely major source. In vivo blockade of extracellular Cyclophilin A signalling substantially attenuated physiological dysfunction, macrophage activation and matrix metalloproteinases. Finally, we found that patients with acute respiratory distress syndrome showed markedly elevated levels of extracellular Cyclophilin A within bronchoalveolar lavage. Conclusions: Cyclophilin A is upregulated within the lungs of injuriously ventilated mice (and critically ill patients), where it plays a significant role in lung injury. Extracellular Cyclophilin A represents an exciting novel target for pharmacological intervention.

BackgroundDespite advances in understanding the pathophysiology of acute respiratory distress syndrome, effective pharmacological interventions have proven elusive. We believe this is a consequence of existing preclinical models being designed primarily to explore biological pathways, rather than predict treatment effects. Here, we describe a mouse model in which both therapeutic intervention and ventilation were superimposed onto existing injury and explored the impact of β-agonist treatment, which is effective in simple models but not clinically.MethodsMice had lung injury induced by intranasal lipopolysaccharide (LPS), which peaked at 48 hours post-LPS based on clinically relevant parameters including hypoxaemia and impaired mechanics. At this peak of injury, mice were treated intratracheally with either terbutaline or tumour necrosis factor (TNF) receptor 1-targeting domain antibody, and ventilated with moderate tidal volume (20 mL/kg) to induce secondary ventilator-induced lung injury (VILI).ResultsVentilation of LPS-injured mice at 20 mL/kg exacerbated injury compared with low tidal volume (8 mL/kg). While terbutaline attenuated VILI within non-LPS-treated animals, it was ineffective to reduce VILI in pre-injured mice, mimicking its lack of clinical efficacy. In contrast, anti-TNF receptor 1 antibody attenuated secondary VILI within pre-injured lungs, indicating that the model was treatable.ConclusionsWe propose adoption of a practical framework like that described here to reduce the number of ultimately ineffective drugs reaching clinical trials. Novel targets should be evaluated alongside interventions which have been previously tested clinically, using models that recapitulate the (lack of) clinical efficacy. Within such a framework, outperforming a failed pharmacologic should be a prerequisite for drugs entering trials.

Aim of the Study Barrett's esophagus (BE) could be a rare late complication in children with repaired esophageal atresia, partly due to a long-term history of gastro-esophageal reflux disease (GERD). Radiofrequency ablation (RFA) is the best endoscopic technique in adults with BE and dysplasia. Guidelines do not support this approach for non-dysplastic BE. Aim of this study is to present our experience as Tertiary Gastroenterology referral Centers in the treatment of children and young adults with BE using RFA. Methods A multicenter retrospective study conducted on children with BE, subjected to RFA at the Digestive Surgery and Endoscopy Unit, Bambino Gesù Children's Hospital and the Department of General Surgery ‘Paride Stefanini’, Sapienza University of Rome, between June 2012 and December 2017.Demographic and clinical data were collected. BE characteristics according to Prague classification, presence and grade of dysplasia, number of RFA treatments, complications, clinic and endoscopic outcomes were described. All patients were treated with HALO RF BARRXtm (HALO 360 Covidien, Sunnyvale, California, USA). Endoscopic evaluation and treatment were performed every 3 months until complete eradication. Endoscopic follow-up was: 6 months after eradication, and then annually. Results Five patients were evaluated (M:5). Mean age at diagnosis was 14.4 years (range: 9–17); mean age at first treatment was 23 years (range: 13–36). Two patients presented with repaired esophageal atresia (long gap, type 3 atresia), 3 with peptic strictures. All patients exhibited a long-term history of symptomatic GERD and PPI dependency. Four patients underwent Nissen fundoplication before BE diagnosis. All patients presented with long segment BE (mean baseline length was 8,8 cm, range 7–10 cm). According to the Prague classification, patients were classified as follows: C0M7, C0M17, C8M10, C0M9 and C4M8. One patient presented with LGD. Patients received a mean of 3 HALO treatments (range 1–4 sessions). Eradication was 100% during 2- to 6-year follow-up (mean 4.5 year). No complications occurred. Conclusions Pediatric patients with EA present an high risk to develop early BE, therefore endoscopic surveillance is mandatory. RFA represents a safe and effective treatment option in patients with early onset BE. Treatment of BE with this technique could be a useful and minimal invasive strategy for dysplasia and cancer prevention.

Foi desenvolvido o modelo bioeconômico nominado de Beef Management System para a obtenção de valores econômicos em quatro sistemas de recria e engorda de bovinos. Dos modelos analisados, dois utilizaram machos inteiros da raça Nelore e os outros dois machos inteiros cruzados (½ sangue taurino; ½ sangue zebu). Para cada grupamento genético estipulou-se dois modelos de produção, um 100 % a pasto e o outro com recria em pastagem e posterior confinamento. O estudo foi conduzido por meio de simulações em planilhas eletrônicas interligadas do programa Microsoft Office Excel. Os valores econômicos foram estimados para as características de ganho médio diário (GMD), rendimento de carcaça (RC), consumo alimentar (CA) e energia de mantença (EM), para cada um dos modelos propostos. Para obtenção dos valores econômicos, estipulou-se um aumento de 1 % no GMD e RC, e diminuiu-se 1 % da EM e CA. Com o aumento de 1 % no RC e no GMD, o custo de produção diminuiu 14,69 kg de carne (1 unidade de arroba) em todos os modelos estudados. A redução de 1 % na EM dos animais resultou em uma diminuição de 0,45 % no custo de produção de 14,69 kg de carne em ambos os modelos a pasto com confinamento e 0,55 % em ambos os modelos 100 % a pasto. Com a redução de 1 % na CA, o custo de produção de 14,69 kg de carne diminuiu 0,83 e 0,84 % nos modelos a pasto com confinamento de animais Nelores e cruzados e 0,85 e 0,83 % nos modelos 100 % a pasto de animais Nelores e cruzados. Essas características possuem um grande impacto econômico nos sistemas de recria e engorda, com grande vantagem para a característica de RC, uma vez que esta proporcionou os maiores valores econômicos para todos os sistemas estudados. Por meio das variáveis que compuseram os modelos estudados tornou-se possível mensurar a real importância do impacto genético das características e seus respectivos valores econômicos.

The PRAME gene plays an important role on reproduction function in cattle and that gene almost present in high copy number in the mammalian genome. Copy number variation (CNV) states have been used in population genetics studies to identify population divergences due to alterations in copy number regions or genes and to identify their impact on economic interest traits, including reproductive traits. The aim of this study was to identify the copy number differences of the PRAME gene within the Gir, Holstein, and Girolando breeds. We analyzed two whole genome sequencing datasets from Girolando bulls, 13 from Gir and five from Holstein. A read depth method was performed using the CNVnator software to detect the CNVs in each sample. To identify the population differentiation among the breeds, the Vst statistic was used. The Vst value (0.77) for the PRAME gene (BTA17:51252501-51660000) indicated a high level of population differentiation among the breeds. The average of the copy number on the PRAME region for the Gir bulls was 14.51 per animal, whereas Girolando and Holstein animals did not exhibit copy number variation in this specific region. Our findings suggested that the PRAME region is copy number variable only in the indicine lineage.This study identified positive selection on the PRAME gene in Gir cattle that may have originated from the domestication process.

When the environment on which the animals are raised is very diverse, selecting the best sires for different environments may require the use of models that account for genotype by environment interaction (G × E). The main objective of this study was to evaluate the existence of G × E for yearling weight (YW) in Nellore cattle using reaction norm models with only pedigree and pedigree combined with genomic relationships. Additionally, genomic regions associated with each environment gradient were identified. A total of 67,996 YW records were used in reaction norm models to calculate EBV and genomic EBV. The method of choice for genomic evaluations was single-step genomic BLUP (ssGBLUP). Traditional and genomic models were tested on the ability to predict future animal performance. Genetic parameters for YW were obtained with the average information restricted maximum likelihood method, with and without adding genomic information for 5,091 animals. Additive genetic variances explained by windows of 200 adjacent SNP were used to identify genomic regions associated with the environmental gradient. Estimated variance components for the intercept and the slope in traditional and genomic models were similar. In both models, the observed changes in heritabilities and genetic correlations for YW across environments indicate the occurrence of genotype by environment interactions. Both traditional and genomic models were capable of identifying the genotype by environment interaction; however, the inclusion of genomic information in reaction norm models improved the ability to predict animals’ future performance by 7.9% on average. The proportion of genetic variance explained by the top SNP window was 0.77% for the regression intercept (BTA5) and 0.82% for the slope (BTA14). Single-step GBLUP seems to be a suitable model to predict genetic values for YW in different production environments.

The Rama are a coastal population from Southern Nicaragua who in large part were able to resist, at least for a time, the cultural changes and social reorganization brought on by colonial and modern influences. Historical information leaves the Rama origins and biological relationships to nearby extinct and extant groups ambiguous. The objective of this study is to examine the internal genetic microdifferentiation based on the first hipervariable region of the mtDNA from a sample of approximately 20% of the population, and to expand the few available historical and anthropological data on the Rama by exploring the effects of cultural practices and historical events on genetic structure, providing an integrative perspective on the Rama genetic history. When considering differences in the spatial distribution and genetic diversity of the mtDNA haplotypes together with historical information on the Rama, a noteworthy pattern emerges: first, haplotypes are differentially distributed among a central Rama community (Punta Águila) from the other five peripheral communities (AMOVA: Fct = 0.10, p < 0.001) and their distribution is consistent with the historical relocation of this population after their split from Punta Gorda in the 18th century; second, differential genetic signatures found among central and peripheral Rama communities resemble two population histories: one of stability (haplogroup A2) and other of expansion (haplogroup B2), supporting the possibility that these patterns of genetic microdifferentiation between central and peripheral populations resulted from the 18th century unification in southern Nicaragua of the Rama and a group of Voto migrants from Costa Rica that later split and hived off to the Bay of Bluefields. UCR::Vicerrectoría de Docencia::Ciencias Sociales::Facultad de Ciencias Sociales::Escuela de Antropología

The Rama Amerindians from southern Nicaragua are one of few indigenous populations inhabiting the east coast and lowlands of southern Central America. Early-eighteenth-century ethnohistorical accounts depicted the Rama as a mobile hunter-gatherer and horticulturalist group dispersed in household units along southern Nicaraguan rivers. However, during the nineteenth and twentieth centuries, Rama settlement patterns changed to aggregated communities because of increased competition for local resources resulting from nonindigenous immigration. The objective of this study was to discern the degree of relatedness between and within subdivisions of seven of these communities based on patterns of surname variation and genealogical data. We applied surname analyses (n = 592) to evaluate inter- and intrapopulation variation, consanguinity and substructure estimates, and isolation by distance and used a genealogically based marital migration matrix obtained during fieldwork in 2007 and 2009 to better understand internal migration. Our evaluation indicates a pattern of geographic distribution linking kinships in major subpopulations to nearby family-based villages. Mantel tests provide a correlation (r = 0.4; p < 0.05) between distance matrices derived from surname and geography among Rama communities. Genealogical analysis reveals a pattern of kin networks within both peripheral and central populations, consistent with previous genetic investigations, where the Amerindian mitochondrial DNA haplogroup B2 is commonly found among peripheral communities and A2 is frequent in central subpopulations. Marital migration and genealogies provide additional information regarding the influx of non-Ramas to communities near populated villages. These results indicate that the disruption of the Rama’s traditional way of life has had significant consequences on their population structure consistent with population fissions and aggregations since the eighteenth century. UCR::Vicerrectoría de Docencia::Ciencias Sociales::Facultad de Ciencias Sociales::Escuela de Antropología UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Biología

Cardiac arrest (CA) is not a uniform condition and its pathophysiology strongly depends on its cause. In this work we have used a metabolomics approach to study the dynamic metabolic changes occurring in the plasma samples of a swine model following two different causes of CA, namely asphyxia (ACA) and ventricular fibrillation (VFCA). Plasma samples were collected at baseline and every minute during the experimental phases. In order to identify the metabolomics profiles characterizing the two pathological entities, all samples were analysed by 1H NMR spectroscopy and LC-MS/MS spectrometry.The metabolomics fingerprints of ACA and VFCA significantly differed during the peri-arrest period and the resuscitation phase. Major alterations were observed in plasma concentrations of metabolites related to tricarboxylic acid (TCA) cycle, urea cycle, and anaplerotic replenishing of TCA. ACA animals showed significant metabolic disturbances during the asphyxial and CA phases, while for VFCA animals this phenomenon resulted shifted at the resuscitation phase. Interestingly, starting from the asphyxial phase, the ACA animals were stratified in two groups based on their metabolomics profiles that resulted to be correlated with the clinical outcome. Succinate overproduction was observed in the animals with the worse outcome, suggesting a potential prognostic role for this metabolite. © 2017 The Author(s).

Hand joint involvement in rheumatic diseases is often precocious and predominant as compared to other skeletomuscular regions. Clinical examination not always allows for easy detection of fluid outpouring and synovial involvement, and undoubtedly does not allow to diagnose pathognomonic bone alterations of several rheumatic conditions. Articular ultrasonography is an innocuous methodology, easily reproducible and directly applied by a rheumatologist. The aim of this vignette is to present ultrasonography elementary lesions of the hand for a prompt diagnosis.

The objective of this study was to identify important biological pathways involved in carcass and meat quality traits that are affected by genes regulated by eQTLs in Nelore cattle. Sample data were acquired from longissimus thoracis of 80 Nelore bulls. RNA sequencing was performed using an Illumina HiSeq 2500 System (2 × 100 base pair paired-end reads). Genotyping was carried out using Illumina BovineHD Infinium Assay ® (777,992 SNPs). After sample outlier removal and genotype filtering, 70 samples were suitable for further analysis with genotypes available for 247,161 SNPs. The eQTL analyses were performed using the R package ‘MatrixEQTL’ under an additive linear model and included multiple-testing correction with a false discovery rate (FDR) of 5%. Reactome pathway enrichment analyses were carried out to the regulated genes. The eQTL analysis identified 1,638 regulated genes that participate in several important biological pathways that may be involved in carcass and meat quality traits in beef cattle, including fatty acid metabolism, B Cell receptor signaling, PPAR signaling, AMPK signaling, non-canonical NF-κB, cytokine signaling, striated muscle contraction, transmission across chemical synapses, apoptosis, receptor tyrosine kinases signaling, GPCR signaling, Wnt signaling, Hedgehog signaling, MAPK signaling, PIP3 activates AKT signaling, Rho GTPases signaling, mTOR signaling, and TNF signaling. Moreover, many genes that have been associated with carcass and meat quality traits in beef cattle are been regulated by eQTLs, such as ACOX1, CAPN2, CAPN7, CASP9, FGF1, HSD17B12, KCNIP4, MYH8, MYL6, MYO5A, SCD5, SLC27A6, and STAT2. These findings show that important biological pathways and genes that affect carcass and meat quality traits are influenced by eQTLs in Nelore cattle, suggesting that eQTL may provide insight into molecular mechanisms underlying economically important traits in beef cattle. Supported by FAPESP #2009/16118-5, #2011/21241-06, #2016/02366-0, and #2017/21757-3.

To study heel fat pad (HFP) inflammatory-oedematous lesions in selected patients with rheumatoid arthritis (RA) using ultrasonography (US) and power Doppler US (PDUS), to describe and compare US features of these lesions with those obtained with magnetic resonance imaging (MRI), and to describe changes in the lesions after a short-term follow-up with conventional or anti-tumour necrosis factor-alpha (TNFalpha) therapy.Twelve heels of eight RA outpatients with HFP inflammatory-oedematous lesions were studied by US, PDUS, and unenhanced MRI. All the patients were followed up and US was performed after 3 months. Five patients started on anti-TNFalpha therapy.HFP lesions appeared at US as a heterogeneous and hypoechoic subcalcaneal mass, with loss of normal lobular structure and increased thickness of HFP, because of focal rupture of fibrous septae with oedema and fluid. PDUS showed peripheral vascularization of HFP lesions in 9/12 heels. In 3/12 heels some vascular signals was also detectable inside the lesion, always along the residual echoic septa. No detectable flow was observed within the central fluid-filled spaces. MRI of the HFP lesions showed areas of mean intensity in T1-weighted sequences and high intensity in T2-weighted sequences, with poorly or well-defined margins. After 3 months, PDUS showed reduction in HFP lesion vascularity (associated with reduction in pain) in 10/12 heels, while poor regression of grey-scale US abnormalities was observed.Both US and MRI are capable of demonstrating structural abnormalities in the HFP. PDUS is useful to assess and monitor inflammatory vascularization of the HFP lesions.

Heel fat pad inflammation and degeneration have been frequently proved to cause talalgia. Painful heel fat pad is often confused with plantar fasciitis, and only magnetic resonance imaging (MRI) or ultrasonography (US) can differentiate these conditions. Scanty data are available about heel fat pad involvement in the course of chronic polyarthritis.To investigate with US the heel fat pad involvement in patients with rheumatoid arthritis (RA) and spondyloarthropathies (SpA); to describe and compare the clinical and sonographic features of this lesion in the two groups.The heels of 181 consecutive outpatients with RA and 160 with SpA were studied by US and radiography. A control group of 60 healthy subjects was examined by US.Two different patterns of involvement of the heel fat pad were observed. The inflammatory-oedematous pattern was more frequent in patients with RA (6.6%) than in those with SpA (1.8%), and was associated with talalgia--even if it was not associated with plantar fasciitis or enthesophyte (bony spur). The degenerative-atrophic pattern was less frequent (1.1% in RA, 1.9% in SpA), and was associated with plantar fasciitis and subcalcaneal enthesophyte.The inflammatory-oedematous lesion of the heel fat-pad is relatively frequent in RA and causes subcalcaneal pain. Degenerative-atrophic changes of the heel fat pad can be observed in RA and SpA, and seem to be associated with chronic abnormalities of the plantar fascia and of its enthesis.

To establish by ultrasonography (US) the frequency of calcaneal entheses involvement in erosive osteoarthritis (EOA), nodal osteoarthritis (NOA), RA and PsA, and to compare these results in order to aid clinicians in the differential diagnosis among these diseases. A comparison between US results and radiography was also made.The heels of 56 consecutive outpatients with EOA, 209 with NOA, 158 with RA and 125 with PsA were studied by US and radiography. A control group of 50 subjects was examined by US.US showed no significant difference in inferior calcaneal enthesophytosis among the four diseases. The frequency of posterioinferior enthesophytosis was lower in RA (34%) in comparison with the other diseases (57% in EOA, 47% in NOA, 49% in PsA). Achilles enthesitis was found in 8% of PsA and in 2% of RA. Retrocalcaneal bursitis was found in 18% of RA and in 6% of PsA. Posterior erosions were present in 12% of RA and 5% of PsA. Inferior erosions were present in 6% of RA and in 1% of PsA. Plantar fasciitis was found in 26% of RA, in 37% of PsA, and in 15% of NOA and 12% of EOA. Subcalcaneal panniculitis was observed in 10% of RA and in 1% of PsA. In the control group, only posterioinferior and inferior enthesophytosis (22% and 18% respectively) were found. Kappa statistics show excellent agreement between US and radiography in detecting posterioinferior (kappa = 0.89) and inferior enthesophytosis (kappa = 0.83), and entheseal erosions (kappa = 0.86).The calcaneal lesions that could be found in EOA are similar to those observed in NOA. The frequency of calcaneal enthesophytosis is similar in EOA, NOA, and PsA, but inflammatory lesions of calcaneal entheses and of the adjacent bursae are more frequent in RA and in PsA. In terms of heel involvement, EOA seems to be similar to NOA. US shows an excellent concordance with radiography in detecting entheseal cortical bone abnormalities.

Enthesitis is an inflammatory lesion of the tendon, ligament and capsular insertions into the bone, and it is a fundamental element in the diagnosis of spondyloarthropathies. Sonography is the method of choice for studying periarticular soft tissues because it is capable of detecting both the early (oedema, thickening) and the late alterations (erosions and enthesophytes); it is also an inexpensive, biologically harmless and easily repeatable technique. The aim of this study was to compare the prevalence of quadricipital enthesitis in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients, and to document any clinical and echostructural differences in this lesion between the two diseases. The results show that enthesitis is more frequent in PsA patients, more than half of whom are asymptomatic. Knee inflammation was found in the PsA patients with enthesitis regardless of the concomitant presence of joint effusion; none of the RA patients suffered from enthesitis alone. Quadricipital enthesitis is more frequent in male patients. There was no significant correlation between the presence of peripatellar psoriatic lesions and enthesitis. Sonographic examinations of patients with enthesitis revealed that those with RA had dominantly inflammatory lesions, whereas PsA patients also showed major new bone deposition.

During the massive mucllage event in the northern Adriatic Sea in July 1991 samples of macroaggregate were fixed in different ways: with formaldehyde, deep frozen and freeze-dried. Conventional microscopy (light and epifluorescence) revealed different autotrophic species embedded in gelatinous matl-ix. Cyanobacteria and heterotrophic bacteria were also identified. Scanning confocal laser microscopy (SCLMI and fluorescent molec~~ la r p obes (the lectins concanavalin A and UEA-I) showed wall-free cytoplasm and particulate polysacchar~des leaklng from the envelopes of broken cells in the matrix. The extensive cell lysis was supported by the observation of cytoplasn1-free cytoskeletons, stained by the molecular probe phalloidin High concentrations of triglycerides (30Y0 of total lipids) and free fatty aclds (22'2%) along with very low concentrations of phospholipids ( 2 % ) also indicated massive cell degradation in freeze-dried material. The mucllage observations were compared with those of a natural plankton community grown under hlgh nutrlent conditions using the same techniques. Free polysaccharides were observed as globular flocs (marine snow) during in situ enrichment experiments and inti-acellular polysaccharides as carbon storage materials In autotrophic organisms. No strings, filaments, layers, cell lysis or lipid classes indicating strong cell biodeterioration were observed in a 1 mo controlled experiment during an algal bloom.

The Rb2/p130 protein has been shown to have a high sequence homology with the retinoblastoma gene product (pRb), one of the most well‐characterized tumor suppressor genes, and with pRb‐related p107, especially in their conserved pocket domains, which display a primary role in the function of these proteins. In this study, we report on the biochemical and immunocytochemical characterization of the Rb2/p130 protein, using a polyclonal antibody developed against its “spacer” region included in the pocket domain of the whole protein. We show that pRb/p130 is a phosphoprotein located at the nuclear level and that its phosphorylation pathway can be dramatically reduced by phosphatase treatment. Moreover pRb/p130, with p107, with p107, is one of the major targets of the E1A viral oncoprotein‐associated kinase activity, showing a phosphorylation pattern which is modulated during the cell cycle, reaching a peak of activation at the onset of S‐phase. © 1995 Wiley‐Liss, Inc. Copyright © 1995 Wiley‐Liss, Inc.

The brain's ability to ignore repeating, often redundant, information while enhancing novel information processing is paramount to survival. When stimuli are repeatedly presented, the response of visually sensitive neurons decreases in magnitude, that is, neurons adapt or habituate, although the mechanism is not yet known. We monitored the activity of visual neurons in the superior colliculus (SC) of rhesus monkeys who actively fixated while repeated visual events were presented. We dissociated adaptation from habituation as mechanisms of the response decrement by using a Bayesian model of adaptation, and by employing a paradigm including rare trials that included an oddball stimulus that was either brighter or dimmer. If the mechanism is adaptation, response recovery should be seen only for the brighter stimulus; if the mechanism is habituation, response recovery ('dishabituation') should be seen for both the brighter and dimmer stimuli. We observed a reduction in the magnitude of the initial transient response and an increase in response onset latency with stimulus repetition for all visually responsive neurons in the SC. Response decrement was successfully captured by the adaptation model, which also predicted the effects of presentation rate and rare luminance changes. However, in a subset of neurons with sustained activity in response to visual stimuli, a novelty signal akin to dishabituation was observed late in the visual response profile for both brighter and dimmer stimuli, and was not captured by the model. This suggests that SC neurons integrate both rapidly discounted information about repeating stimuli and novelty information about oddball events, to support efficient selection in a cluttered dynamic world.

The aim of this study was to evaluate the frequency of altered expression of pRb and p53, two well known tumor suppressor genes, in lung cancer and to relate it to the prognosis of the patients affected by this type of neoplasm. We evaluated 68 specimens from patients with surgically resected lung cancer. Of the 68 neoplasms investigated, 29 (42.6%) displayed a positive nuclear staining for p53. Ten (15.7%) of the investigated tumors showed absence of pRb nuclear immunoreactivity. p53 overexpression correlated statistically with short-term survival. On the other hand no statistically significant difference (p=ns) in survival was detected between pRb producers and nonproducer patients. In addition, we divided our specimens into two groups according to the p53 and pRb status. The first group consisted of all the p53(+) pRb specimens. The second group contained all the remaining specimens. Comparison between these two groups did not reveal any significant difference in overall survival time. These findings confirm that only p53 overexpression can be considered an independent prognostic factor in lung cancer.

Aims: To investigate Klebsiella oxytoca strain BAS-10 growth on ferric citrate under anaerobic conditions for exopolysaccharide (EPS) production and localization on cell followed by the purification and the EPS determination of the iron-binding stability constant to EPS or biotechnological applications. Methods and Results: Klebsiella oxytoca ferments ferric citrate under anaerobic conditions and produces a ferric hydrogel, whereas ferrous ions were formed in solution. During growth, cells precipitate and a hydrogel formation was observed: the organic material was constituted of an EPS bound to Fe(III) ions, this was found by chemical analyses of the iron species and transmission electron microscopy of the cell cultures. Iron binding to EPS was studied by cyclic voltammetric measurements, either directly on the hydrogel or in an aqueous solutions containing Fe(III)-citrate and purified Fe(III)-EPS. From the voltammetric data, the stability constant for the Fe(III)-EPS complex can be assumed to have values of approx. 1012–1013. It was estimated that this is higher than for the Fe(III)-citrate complex. Conclusions: The production of Fe(III)-EPS under anaerobic conditions is a strategy for the strain to survive in mine drainages and other acidic conditions. This physiological feature can be used to produce large amounts of valuable Fe(III)-EPS, starting from a low cost substrate such as Fe(III)-citrate. Significant and Impact of the Study: The data herein demonstrates that an interesting metal-binding molecule can be produced as a novel catalyst for a variety of potential applications and the EPS itself is a valuable source for rhamnose purification.

In Italy at least 3% of babies are born with some congenital malformation. The intake of folic acid (FA) prior to conception and during the early stages of pregnancy plays an important role in preventing neural tube defects, severe anomalies of brain embryogenesis, and other malformations such as cardiac and urinary tract anomalies, oro-facial clefts and limb reduction defects. The Italian Network for Folic Acid Promotion, coordinated by the National Center on Rare Diseases of the Italian National Institute of Health, has elaborated and diffused a recommendation for the periconceptional FA supplementation: "Women of child-bearing age, are recommended to consume 0,4 mg/day of FA, to reduce the risk of congenital defects. The intake of folic acid should start at least one month before the conception and should continue for the first quarter of pregnancy". This paper discusses various strategies in order to promote FA intake during periconceptional period. Food fortification, adopted in several countries such as USA, has raised concerns about the risk of an excessive FA intake which may lead to adverse effect such as tumour promotion. Currently, periconceptional supplementation and healthy dietary habits promotion appear to be the most effective strategies.

JIA is a chronic disease that can involve many different joints including TMJ. TMJ involvement leads to: chewing function alteration due to synovial membrane thickening, masticator muscle weakness and facial pain; craniofacial growth disturbance (micrognathia or facial asymmetry). The aim of our study is to evaluate the TMJ in people affected by JIA for early diagnosis of TMJ arthritis. Our series included 51 consecutive patients with JIA, 16 males and 35 females (age range 4 – 19 years), that were evaluated through a rheumatologic and dentist examination. Clinically suspected cases were studied with Magnetic Resonance Imaging (MRI). Our results showed that 19/51 patients (37%) (age range 9 – 19 years) had TMJ alterations, 10/19 (19,6%) concerning the left one while 7/19 (13,7%) the right one. Only 2/19 (4%) had a bilateral involvement. TMJ arthritis can severely affect the growth of mandibular, it can be asymptomatic in the majority of cases but it is present in about 50% of children with JIA. MRI is useful to evidence the assessment of disease activity with precious informations about its evolution. Besides, this imaging technique allows to eliminate X-rays exposure and, in according to its high definition, can show early joints alterations also in apparently asymptomatic children. In our patients, MRI was the gold standard for an early diagnosis showing that 37% of cases had TMJ involvement.

Objective: To assess the efficacy of Cellfood®’s therapy in the treatment of fibromyalgia. Methods: This study was a single-blind, cross-over, randomized placebo-controlled trial. Fourty female were selected from 320 cases investigated in the period 2003-2005 of june. To be included in this study, it was required that the diagnosis of fibromyalgia was made by a specialist in according to the ACR classification criteria of 1990. The patient’s age was between 35-47 years, the choice of criteria were the absence of improvements with the conventional therapy and the normality of medical check-up. The patients were divided into two different-groups of thirty-one and nine subjects, each-one (group A) treated with Cellfood® for six months in according to the Eurodream’s scheme, and each-other (group B) treated with placebo for three months and successively with Cellfood® for three months.Besides we have estimated the tender points with algometer and the health status of women with the Fibromyalgia Impact Questionnaire (FIQ) at the baseline (T0) and at three (T1) and six month (T2). Result: The group A had an appreciable improvement of the parameters at T1 statistically significant compared to the group B, while we observed a stability of they at T2 on the group A and an improvementof the parameters of the group B statistically non significant compared to each-one. Conclusion: Our result suggest that the Cellfood®’s therapy improve fibromyalgia symptoms and health-related quality of life.

Bisphosphonates (BPs) are pharmacological compounds widely used in the treatment of a variety of bone-related diseases, particularly where the bone-turnover is skewed in favour of osteolysis. The mechanisms by which BPs reduce bone-resorption directly acting on osteoclasts (OCs) are now largely clarified even at molecular level. The researches concerning the BPs effects on osteoblasts (OBs) have instead shown variable results. Objectives: We have investigated the efficacy of neridronate (NER), an amino-BP, as anabolic agent on human OBs. Moreover, we have tried to verify if NER is able to negatively modulate the production of IL-6 on OBs stimulated or not by the pro-inflammatory cytokine Il-1b. Methods: We have tested if different concentrations of NER (from 10-11M to 10-3M), added to primary human OB cultures, could affect the cells number, the endogenous cellular alkaline phosphatase (ALP) activity, the collagen I (COLI) synthesis, the formation of mineralized nodules and the IL-6 production. Our experimental approach was performed testing a wide range of NER concentrations because, under physiological conditions, OBs seems to be exposed to variable and transient levels of the drug. Results: Our results show that NER doesn’t negatively affect in vitro the viability, proliferation and cellular activity of human OBs, even after 20 days of exposure to concentrations ²10-5 M (therapeutic dose). In addition, NER seems to enhance the differentiation of cultured OBs in mature bone-forming cells. A maximum increase of COL-I synthesis (+25% after 4 days; p

According to the criteria proposed by Ryan and McCarty,1 the diagnosis of calcium pyrophosphate dihydrate (CPPD) deposition disease has been based on radiological evidence of the characteristic calcifications and on verification of the synovial liquid of CPPD crystals. Joint ultrasonography is an innocuous diagnostic technique that is well tolerated by patients, and is the elected method for observing calcified deposits in soft tissues.2 We carried out a longitudinal study, enrolling patients affected with ultrasonographic chondrocalcinosis according to previously proposed criteria3 from a sample of consecutive patients that came to our joint ultrasonography department for gonalgia (fig. 1). A total of 47 patients were identified, of which 14 had joint effusion. Figure 1 Hyperechoic deposits. Deposits (arrows) are shown that are compatible with calcium pyrophosphate dihydrate (CPPD) calcifications in the context of the synovial membrane (1), hyaline cartilage of the …