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Previous studies have described the clinical, serological and pathological features of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and antibodies directed against the paranodal proteins neurofascin-155, contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), or nodal forms of neurofascin. Such antibodies are useful for diagnosis and potentially treatment selection. However, antibodies targeting Caspr1 only or the Caspr1/CNTN1 complex have been reported in few patients with CIDP. Moreover, it is unclear if these patients belong to the same pathophysiological subgroup. Using cell-based assays in routine clinical testing, we identified sera from patients with CIDP showing strong membrane reactivity when both CNTN1 and Caspr1 were co-transfected (but not when CNTN1 was transfected alone). Fifteen patients (10 male; aged between 40 and 75) with antibodies targeting Caspr1/CNTN1 co-transfected cells were enrolled for characterization. The prevalence of anti-Caspr1/CNTN1 antibodies was 1.9% (1/52) in the Sant Pau CIDP cohort, and 4.3% (1/23) in a German cohort of acute-onset CIDP. All patients fulfilled European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite diagnostic criteria for CIDP. Seven (47%) were initially diagnosed with Guillain-Barré syndrome due to an acute-subacute onset. Six (40%) patients had cranial nerve involvement, eight (53%) reported neuropathic pain and 12 (80%) ataxia. Axonal involvement and acute denervation were frequent in electrophysiological studies. Complete response to intravenous immunoglobulin was not observed, while most (90%) responded well to rituximab. Enzyme-linked immunosorbent assay (ELISA) and teased nerve fibre immunohistochemistry confirmed reactivity against the paranodal Caspr1/CNTN1 complex. Weaker reactivity against Caspr1 transfected alone was also detected in 10/15 (67%). Sera from 13 of these patients were available for testing by ELISA. All 13 samples reacted against Caspr1 by ELISA and this reactivity was enhanced when CNTN1 was added to the Caspr1 ELISA. IgG subclasses were also investigated by ELISA. IgG4 was the predominant subclass in 10 patients, while IgG3 was predominant in other three patients. In conclusion, patients with antibodies to the Caspr1/CNTN1 complex display similar serological and clinical features and constitute a single subgroup within the CIDP syndrome. These antibodies likely target Caspr1 primarily and are detected with Caspr1-only ELISA, but reactivity is optimal when CNTN1 is added to Caspr1 in cell-based assays and ELISA.

Background and ObjectivesTo study the clinical and laboratory features of antineurofascin-155 (NF155)–positive autoimmune nodopathy (AN).MethodsPatients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up.ResultsForty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2–4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = −0.88, p < 0.001) and with maximum I-RODS achieved (r = −0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients.DiscussionAnti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases.Classification of EvidenceThis study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab.

Recent estimations of the Hubble parameter $H_0$ based on gravitational waves (GW) observations can be used to shed some light on the discrepancy between the value of the Hubble parameter $H_0^P$ obtained from large scale observations such as the Planck mission, and the small scale value $H_0^R$, obtained from low redshift supernovae (SNe). In order to investigate the origin of this discrepancy we perform a combined analysis of the luminosity distance of SNe and GW sources, using different methods, finding that the impact of the GW data is very limited, due to the small number of data points, and their large errors. We analyze separately data from the Pantheon and the Union 2.1 catalogues, finding that a model with $H_0^P$ and a small local void can fit the data as well as a homogeneous model with $H_0^R$, resolving the apparent $H_0$ tension. We find that there is a significant difference between the size and depth of the inhomogeneity obtained using the two datasets, which could be due to the different sky coverage of the two catalogues. For Pantheon we obtain evidence of a local inhomogeneity with a density contrast $\delta_v=-0.155 \pm 0.026$, extending up to a redshift of $z_v = 0.056 \pm 0.0002$, while for Union 2.1 we obtain $\delta_v=-0.461 \pm 0.032$ and $z_v= 0.081\pm 0.008$. We also perform some analysis using redshift shell averaged data, and obtain approximately the same results, hinting to the fact that the effects of the monopole component of the local inhomogeneity are the dominant ones

Equine piroplasmosis (EP) is a tick-borne disease caused by Babesia caballi and Theileria equi, which causes severe economic losses to the equine industry, represented by the Spanish Purebred (SP) horse in Spain. The seroprevalence of EP is known in certain regions of Spain, but till date, there are no data in SP horses. The aim of this study was to determine the seroprevalence of EP in the SP breeding horse population in central Spain and to evaluate risk factors associated with the occurrence of the infection. A total of 536 horse serum samples were tested for antibodies against T. equi and B. caballi by competitive inhibition enzyme-linked immunosorbent assay. Data on possible risk factors were examined using two logistic regression models with and without a random effect at the stud farm level. The true seroprevalence results were 21.8% for T. equi and 4.7% for B. caballi. Increasing horse age and increasing numbers of breeding stallions on the stud farm were identified as factors associated with EP seropositivity. The implementation of vaccination programs in the horses and disinfection measures in the premises were associated with a lower T. equi and B. caballi seroprevalence, respectively. A moderate exposure to EP was found in SP horses in central Spain. Further investigations are necessary to ensure appropriate preventive measures for stud farms and to facilitate the development of an EP surveillance program in the SP breeding horse population.

Summary Duchenne muscular dystrophy (DMD), one of the most lethal genetic disorders, involves progressive muscle degeneration resulting from the absence of DYSTROPHIN. Lack of DYSTROPHIN expression in DMD has critical consequences in muscle satellite stem cells including a reduced capacity to generate myogenic precursors. Here, we demonstrate that the c-isoform of PITX2 transcription factor modifies the myogenic potential of dystrophic-deficient satellite cells. We further show that PITX2c enhances the regenerative capability of mouse DYSTROPHIN-deficient satellite cells by increasing cell proliferation and the number of myogenic committed cells, but importantly also increasing dystrophin-positive (revertant) myofibers by regulating miR-31. These PITX2-mediated effects finally lead to improved muscle function in dystrophic (DMD/mdx) mice. Our studies reveal a critical role for PITX2 in skeletal muscle repair and may help to develop therapeutic strategies for muscular disorders., Highlights • PITX2c is required for proper satellite cell differentiation • PITX2c rescues impaired myogenic potential of dystrophic satellite cells • PITX2c promotes muscle regeneration in dystrophic DMD/mdx mice • PITX2c increases revertant DYSTROHIN in DMD/mdx mice by downregulating miR-31, Vallejo et al. show that PITX2c enhances the regenerative capability of mouse DYSTROPHIN-deficient satellite cells by increasing cell proliferation and the number of myogenic committed cells but importantly also increasing dystrophin-positive (revertant) myofibers by regulating miR-31.

We propose a novel deep learning tool in order to study the evolution of dark energy models. The aim is to combine two architectures: the Recurrent Neural Networks (RNN) and the Bayesian Neural Networks (BNN), we named this full network as RNN+BNN. The first one is capable of learning complex sequential information to classify objects like supernovae and use the light-curves directly to learn information from the sequence of observations. Since RNN is not capable to calculate the uncertainties, BNN emerges as a solution for problems in deep learning like, for example, the overfitting. For the trainings we use measurements of the distance modulus $\mu(z)$, such as those provided by Pantheon Supernovae Type Ia. In view of our results, the reported approach turns out to be a first promising step on how we can train a new neural network that can compute their own confidence regions for specific cosmological data. It is worth stressing that the new technique allows to reduce the computational load of expensive codes for dark energy models and probe the necessity of modified dark energy models at large redshifts for a supernovae trained sampler., Comment: 22 pages, 8 figures. Version accepted for publication in JCAP

TRIM32 is a E3 ubiquitin -ligase containing RING, B-box, coiled-coil and six C-terminal NHL domains. Mutations involving NHL and coiled-coil domains result in a pure myopathy (LGMD2H/STM) while the only described mutation in the B-box domain is associated with a multisystemic disorder without myopathy (Bardet-Biedl syndrome type11), suggesting that these domains are involved in distinct processes. Knock-out (T32KO) and knock-in mice carrying the c.1465G > A (p.D489N) involving the NHL domain (T32KI) show alterations in muscle regrowth after atrophy and satellite cells senescence. Here, we present phenotypical description and functional characterization of mutations in the RING, coiled-coil and NHL domains of TRIM32 causing a muscle dystrophy. Reduced levels of TRIM32 protein was observed in all patient muscle studied, regardless of the type of mutation (missense, single amino acid deletion, and frameshift) or the mutated domain. The affected patients presented with variable phenotypes but predominantly proximal weakness. Two patients had symptoms of both muscular dystrophy and Bardet-Biedl syndrome. The muscle magnetic resonance imaging (MRI) pattern is highly variable among patients and families. Primary myoblast culture from these patients demonstrated common findings consistent with reduced proliferation and differentiation, diminished satellite cell pool, accelerated senescence of muscle, and signs of autophagy activation., Supported in part by grants from the Health Institute Carlos III and FEDER a way to achieve Europe (PI16–01843 to CP, JR15/00042 to MC-S), the Fundación Progreso y Salud, Junta de Andalucía (PI-0085-2016 to JLN-G), and Australian National Health and Medical Research Council (NHMRC) Fellowships (APP1122952 and APP1117510 to GR and NGL).

La región Andina en Colombia alberga al menos 192 especies de mamíferos silvestres. No obstante, es una región altamente transformada, así que el establecimiento y monitoreo de reservas es fundamental para el mantenimiento de la biodiversidad. Realizamos el inventario de los mamíferos silvestres de la Reserva Natural Hacienda San Pedro, Maceo, Antioquia. Se registran 40 especies pertenecientes a ocho órdenes y 17 familias. Se encontraron especies amenazadas y endémicas como Saguinus leucopus, Aotus griseimembra, Notosciurus pucheranii y Proechimys crysaeolus. El ensamblaje del sitio presentó especies frecuentes de la región del Magdalena Medio, así como de los Andes Centrales. Esperamos que este trabajo sea un aporte a las prácticas académicas que se llevan a cabo en la reserva y que resalte su aporte a la conservación de los mamíferos silvestres a nivel regional.

Serological analysis of equine piroplasmosis (EP), caused by Theileria equi and Babesia caballi, is included in the export testing requirements for most of the countries worldwide, thus involving a high economic impact on equine industry of EP-endemic countries, such as Spain. A total of 3368 serum samples from healthy horses collected prior to export between 2015 and 2018 in Spain were tested for antibodies against T. equi and B. caballi by using a competitive inhibition enzyme-linked immunosorbent assay (cELISA). The overall seroprevalence results in Spain revealed that almost a quarter of the horses analysed (24.1 %; 95% CI 22.6-25.5) could not be exported to countries free from EP. The implementation of prevention measures such as the use of acaricides and daily checks for ticks in horses, as well as regular serological screening of horses in Spain would aid to increase the number of horses exported to other countries.

Equine piroplasmosis (EP) is a tick-borne protozoan disease caused by Theileria equi and/or Babesia caballi. Clinical signs (fever, pale mucosal membranes, jaundice), anemia and hyperbilirubinemia have been associated with the disease. EP is widespread, has a significant economic impact on the equine industry and remains endemic in Spain. This study was carried out with samples belonging to 140 horses residing in Spain and showing common clinical signs of EP. A blood smear microscopic examination and a comparison between the different results obtained by competitive Enzyme-Linked Immunosorbent Assay (cELISA), real-time Polymerase Chain Reaction (PCR) and hematological and biochemical (direct and total bilirubin) screening were conducted. EP positivity rates by cELISA and PCR were 50.7% and 42.9%, respectively, whereas only 9% of the horses were positive in the microscopic analysis. A significantly higher number of B. caballi-positive horses were detected by cELISA than PCR, and Kappa value was higher for T. equi (k = 0.575) than for B. caballi (k = 0.401). For the first time, an association between a high ELISA inhibition percentage (IP) and a positive PCR result for B. caballi was determined. Although most authors have described T. equi as more pathogenic than B. caballi, we found that horses parasitized by B. caballi showed a more severe hemolytic anemia, whereas T. equi infections were mostly associated with leukocytosis. The hemogram and clinical chemistry could guide the veterinary surgeon towards the diagnosis of T. equi or B. caballi since horses showed a significant leukocytosis or anemia and hyperbilirubinemia, respectively; however PCR would be the test of choice in order to confirm the diagnosis. Information about the importance of a correct diagnosis of EP using a combination of techniques is essential in order to allow the early detection of cases and prevent the spread of the disease, as well as to avoid the common practice of treating horses without a laboratory diagnosis.

ObjectiveTo describe a large series of BIN1 patients, in which a novel founder mutation in the Roma population of southern Spain has been identified.MethodsPatients diagnosed with centronuclear myopathy (CNM) at 5 major reference centers for neuromuscular disease in Spain (n = 53) were screened for BIN1 mutations. Clinical, histologic, radiologic, and genetic features were analyzed.ResultsEighteen patients from 13 families carried the p.Arg234Cys variant; 16 of them were homozygous for it and 2 had compound heterozygous p.Arg234Cys/p.Arg145Cys mutations. Both BIN1 variants have only been identified in Roma, causing 100% of CNM in this ethnic group in our cohort. The haplotype analysis confirmed all families are related. In addition to clinical features typical of CNM, such as proximal limb weakness and ophthalmoplegia, most patients in our cohort presented with prominent axial weakness, often associated with rigid spine. Severe fat replacement of paravertebral muscles was demonstrated by muscle imaging. This phenotype seems to be specific to the p.Arg234Cys mutation, not reported in other BIN1 mutations. Extreme clinical variability was observed in the 2 compound heterozygous patients for the p.Arg234Cys/p.Arg145Cys mutations, from a congenital onset with catastrophic outcome to a late-onset disease. Screening of European Roma controls (n = 758) for the p.Arg234Cys variant identified a carrier frequency of 3.5% among the Spanish Roma.ConclusionWe have identified a BIN1 founder Roma mutation associated with a highly specific phenotype, which is, from the present cohort, the main cause of CNM in Spain.

Background The aim of the research is to study the human leukocyte antigen (HLA) class II allele frequencies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with anti-neurofascin 155 (NF155) antibodies. Methods Thirteen anti-NF155+ and 35 anti-NF155 negative (anti-NF155neg) CIDP patients were included in a case-control study. The frequencies of the DRB1 HLA allele were analyzed in all patients while DQ frequencies were only studied in patients sharing the DRB1*15 allele. In silico HLA-peptide binding and NF155 antigenicity, predictions were performed to analyze overlap between presented peptides and antigenic regions. Results DRB1*15 alleles (DRB1*15:01 and DRB1*15:02) were present in 10 out of 13 anti-NF155+ CIDP patients and in only 5 out of 35 anti-NF155neg CIDP patients (77 vs 14%; OR = 20, CI = 4.035 to 99.13). DRB1*15 alleles appeared also in significantly higher proportions in anti-NF155+ CIDP than in normal population (77 vs 17%; OR = 16.9, CI = 4.434 to 57.30). Seven anti-NF155+ CIDP patients (53%) and 5 anti-NF155neg CIDP patients had the DRB1*15:01 allele (OR = 7, p = 0.009), while 3 anti-NF155+ CIDP patients and none of the anti-NF155neg CIDP patients had the DRB1*15:02 allele (OR = 23.6, p = 0.016). In silico analysis of the NF155 peptides binding to DRB1*15 alleles showed significant overlap in the peptides presented by the 15:01 and 15:02 alleles, suggesting functional homology. Conclusions DRB1*15 alleles are the first strong risk factor associated to a CIDP subset, providing additional evidence that anti-NF155+ CIDP patients constitute a differentiated disease within the CIDP syndrome. Electronic supplementary material The online version of this article (10.1186/s12974-017-0996-1) contains supplementary material, which is available to authorized users.

Histiocytic sarcomas are rare neoplasms with poor prognosis originating from histiocytic or dendritic cell clones and associated with haematological malignancies such as acute or chronic leukemias and lymphomas. We describe a case of a patient who developed a disseminated and extensive mucocutaneous histiocytic sarcoma during remission. UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicina

Cyclin D1(-) mantle cell lymphomas (MCLs) are not well characterized, in part because of the difficulties in their recognition. SOX11 has been identified recently as a reliable biomarker of MCL that is also expressed in the cyclin D1(-) variant. We investigated 40 lymphomas with MCL morphology and immunophenotype that were negative for cyclin D1 expression/t(11;14)(q13;q32) but positive for SOX11. These tumors presented clinically with generalized lymphadenopathy, advanced stage, and poor outcome (5-year overall survival, 48%). Chromosomal rearrangements of the CCND2 locus were detected in 55% of the cases, with an IG gene as partner in 18 of 22, in particular with light chains (10 IGK@ and 5 IGL@). No mutations in the phosphorylation motifs of CCND1, CCND2, or CCND3 were detected. The global genomic profile and the high complexity of the 32 cyclin D1(-) SOX11(+) MCL patients analyzed by copy number arrays were similar to the conventional cyclin D1/SOX11 MCL. 17p deletions and high Ki67 expression conferred a significantly worse outcome for the patients. This comprehensive characterization of a large series of cyclin D1(-) MCL patients indicates that these tumors are clinically and biologically similar to the conventional cyclin D1(+) MCL and provides a basis for the proper identification and clinical management of these patients.

Summary 1. Precipitation is considered to be a key driver of ecosystem processes in mesic grasslands, and climate models predict changes in the amount and intensity of precipitation under future global change scenarios. Although most experimental rainfall studies decrease precipitation, seasonal rainfall is predicted to increase in the northern Great Plains under climate change. 2. We analysed changes in community composition and structure of upland and lowland native tallgrass prairie in central Kansas, USA, subjected to 19 years of irrigation designed to eliminate moisture stress throughout the growing season. 3. Irrigation had limited effects on species richness in both upland and lowland prairie. Total cover increased significantly and consistently with irrigation in drier uplands and in more mesic lowlands. Abundance of rhizomatous, tall, perennial species as well as C3 forbs increased with irrigation. 4. The strongest response to irrigation came within the dominant functional type, C4 perennial grasses. Panicum virgatum became the dominant species in irrigated lowlands, whereas Andropogon gerardii remained the dominant species in irrigated uplands and in control plots. Overall, irrigation had less effect on community composition and structure than other known drivers of grassland structure and function. 5. In comparison with other studies, our results demonstrate that water addition has less of an impact than fire, grazing or nitrogen addition on composition and dynamics in this mesic grassland. The strongest response to long-term irrigation occurred within the dominant functional type: tall, perennial, rhizomatous, C4 grasses. Thus, functional redundancy will buffer this ecosystem from potential increases in rainfall due to climate change. Finally, our results highlight the limited utility of qualitative functional traits to predict how this mesic grassland will respond to climate change.

Opossums and rodents were sampled by live-trapping at Paracou, French Guiana to study habitat use. Tomahawk and Sherman traps were placed on the ground and at various heights in the subcanopy and canopy. We captured 10 species of opossums and seven species of rodents. We measured 14 microhabitat variables at each of 485 sampling stations. Presence or absence at a trap station of the three most abundant species of opossums (Didelphis albiventris, Didelphis marsupialis, and Micoureus demerarae) and two rodents (Oecomys rutilus and Proechimys cuvieri) were related by logistic regression analysis to the microhabitat variables. All five species were associated with at least one habitat variable. Linear analysis of categorical data was used to determine the degree of arboreality. Didelphis marsupialis and P. cuvieri were more commonly captured on the ground, D. albiventris was equitably distributed between ground and arboreal traps, and the remaining species were mostly arboreal. Linear analysis was used to compare the distribution of arboreal captures among two substrate types, two heights, and two substrate diameters. Oecomys rutilus was more commonly captured on lianas, D. albiventris and O. rutilus were more commonly captured at lower heights, and D. marsupialis demonstrated a preference for larger arboreal substrates.

Background Cyclin D1-positive B cells are occasionally found in the mantle zones of reactive lymphoid follicles, a condition that has been called 'in situ mantle cell lymphoma'. The clinical significance of this lesion remains uncertain. Design and Methods The clinical and pathological characteristics, including SOX11 expression, of 23 cases initially diagnosed as in situ mantle cell lymphoma were studied. Results Seventeen of the 23 cases fulfilled the criteria for in situ mantle cell lymphoma. In most cases, the lesions were incidental findings in reactive lymph nodes. The t(11; 14) was detected in all eight cases examined. SOX11 was positive in seven of 16 cases (44%). Five cases were associated with other small B-cell lymphomas. In two cases, both SOX11-positive, the in situ mantle cell lymphoma lesions were discovered after the diagnosis of overt lymphoma; one 4 years earlier, and one 3 years later. Twelve of the remaining 15 patients had a follow-up of at least 1 year (median 2 years; range, 1-19.5), of whom 11 showed no evidence of progression, including seven who were not treated. Only one of 12 patients with an in situ mantle cell lymphoma lesion and no diagnosis of mantle cell lymphoma at the time developed an overt lymphoma, 4 years later; this case was also SOX11-positive. The six remaining cases were diagnosed as mantle cell lymphoma with a mantle zone pattern. Five were SOX11-positive and four of them were associated with lymphoma without a mantle zone pattern. Conclusions In situ mantle cell lymphoma lesions are usually an incidental finding with a very indolent behavior. These cases must be distinguished from mantle cell lymphoma with a mantle zone pattern and overt mantle cell lymphoma because they may not require therapeutic intervention.

Aim We examine the influence of geography on species richness and endemism of mammals on tropical Pacific archipelagos to determine the importance of intra- and inter-archipelago speciation in promoting local and regional species richness. Location Thirty tropical Pacific archipelagos. Methods A distributional list of mammals on 30 archipelagos was compiled, and values for 10 geographical variables were estimated for each archipelago. Mammal species were placed in three different categories (continental, Pacific and endemic) based on their distribution. The total number of species and numbers of species within each category were related to the geographical variables using Poisson regression analysis. Results Species richness was related positively to variables describing land area, numbers of large islands and elevation; and negatively to variables describing isolation. Levels of endemism did not differ between volant and non-volant species, but differed between mega- and microchiropterans. Main conclusions Variation in species richness of mammals in the tropical Pacific region can be accounted for by a combination of intra-archipelago speciation within archipelagos composed of large islands, and inter-archipelago speciation, particularly among more isolated archipelagos. Mammals were less widely distributed throughout the study area than previously found for butterflies, skinks or birds. However, the level of endemism was similar to that of skinks and birds on the same archipelagos, and was higher than that of butterflies.

We examined the possible involvement of polymorphisms of the presenilin 1 (PS1) and presenilin 2 (PS2) genes in the risk for sporadic Alzheimer's disease (AD), either through an independent effect or through interaction with the existing apolipoprotein E (ApoE) risk, in 211 AD cases and 188 age-matched control subjects. No significant differences were obtained in any of the comparisons relating the effect of the PS1 and PS2 polymorphisms; thus, these polymorphisms do not appear to be sufficient risk factors by themselves for sporadic AD. Although the ApoE varepsilon4 genotype is the only definite predictor of risk, homozygosity for either the 1 allele of the PS1 or the C allele of the PS2 genes may increase the risk conferred by the presence of an ApoE epsilon4 allele. Additionally, combination of PS1/11 and PS2/CC genotypes might have a small synergistic effect on the risk for AD.

The differential diagnosis between neoplastic and reactive lymphoid proliferations is a relatively common situation, which in most cases is resolved using conventional morphological and phenotypic criteria. In the last years, a number of studies have identified different types of lymphoid lesions sharing pathological and molecular features of both benign and malignant processes that are difficult to interpret. A group of these lesions correspond to atypical lymphoid hyperplasias, including follicular hyperplasias, atypical marginal zone hyperplasias, and florid reactive lymphoid hyperplasias of the lower female genital tract in which immunoglobulin light chain restriction with or without clonal IGH rearrangements may be found in some cases. However, these lesions are usually self-limited and do not evolve to an overt lymphoid neoplasia. A second group of lesions are clonal expansions of cells with phenotypic or molecular features of well-defined lymphoid neoplasias, such as chronic lymphocytic leukemias, follicular lymphomas, or mantle cell lymphomas, occurring in otherwise healthy individuals or in the context of reactive lymphoid tissues. In this review, we discuss the criteria to distinguish these lesions from overt lymphomas and the current recommendations for the management of the individuals in which these lesions are found.

The World Health Organization (WHO) classification of the lymphoid neoplasms updated in 2008 represents a worldwide consensus on lymphoma diagnosis and is based in two major principles: the stratification of neoplasms according to their cell lineage and their derivation of precursor or mature cells and the definition of non-overlapping distinct diseases that are clinically relevant. The identification of these diseases is based on a combination of morphology, immunophenotype, genetic, molecular, and clinical features. In addition to well-defined entities, the classification addresses open issues, such as provisional entities that correspond to categories for which there were insufficient evidence to support its recognition as distinct diseases at the time of publication and borderline categories with overlapping features between large B-cell lymphomas and Burkitt or Hodgkin lymphoma.

We report a 52 years old male patient who presented with acute inflammatory rightperiorbital process and febrile syndrome. Hepatosplenomegaly was documented, a rightretro orbital mass, without lymphadenopathy,with laboratories that support the diagnosis ofhemophagocytic syndrome, chronic hepatitis B. Peripheral T-cell lymphoma was documented inretro orbital and liver tissue, we discuss theprevalence of peripheral T-cell lymphoma associated with hemophagocytic syndrome. Se presenta el caso de un paciente de 52 años que consulta por cuadro agudo de procesoinflamatorio peri orbital derecho y síndrome febril. Se documenta hepato esplenomegalia, masa retroorbitaria derecha, sin adenopatías, laboratorios que apoyan el diagnóstico de síndrome hemofagocítico, hepatitis B crónica y linfoma Tperiférico no especificado en tejido retroorbitario e hígado. Se discute sobre la prevalencia de linfoma T periférico asociado a síndrome hemofagocítico.

Background Reactivity against terminal NeuNAc(α2–3)Gal, common to several gangliosides such as GD1a, GT1b and GM3, has rarely been reported. The authors recently described a patient with a clinical picture of acute relapsing sensory ataxic neuropathy and bulbar involvement in whom they demonstrated concomitant reactivity against NeuNAc(α2–3)Gal and disialosyl epitopes. The authors suggested a correlation between NeuNAc(α2–3)Gal reactivity and bulbar involvement. Aim To determine the frequency of reactivity against terminal NeuNAc(α2–3)Gal in acute and chronic immune-mediated disorders, and its possible correlation with bulbar involvement. Methods The authors retrospectively reviewed reactivity in the serum of more than 3000 consecutive patients with acute and chronic disorders in which antiganglioside antibodies were studied. The authors selected those patients who were simultaneously positive, by ELISA or thin-layer chromatography, for IgG or IgM antibodies anti-GM3, GD1a and GT1b, and reviewed their clinical features. Results Reactivity against NeuNAc(α2–3)Gal, shared by GM3, GD1a and GT1b gangliosides, was detected in 10 patients: isolated in one patient, and concomitant with reactivity against other gangliosides in the remaining patients. Reactivity against NeuNAc(α2–3)Gal was frequently associated (8/10) with symptoms suggestive of bulbar involvement, such as dysphagia, dysarthria or dysphonia. Severe respiratory failure requiring mechanical ventilation was observed in four patients. Conclusions Reactivity against the NeuNAc(α2–3)Gal epitope is rare and is generally found in association with reactivity against the disialosyl epitope. It can be detected in patients with acute or chronic disorders and could be a serological marker of clinical bulbar involvement and, to a lesser extent, associated with the development of severe respiratory failure.

Botfly larvae (Cuterebra sp.) infesting spiny rats (Proechimys semispinosus) in 8 small islands in the Panama Canal were studied. Rats were live trapped monthly on each island from January 1991 through February 2000 and visually examined for the presence of bots. Overall, bot prevalence was 4.6% and differed statistically among island rat populations. Rats were simultaneously infested by as many as 4 bots. Overall bot intensity was 1.3 bots per infested rat and did not differ among islands. Mean bot density across all islands was 0.0111 and was greater during the dry seasons than during the rainy seasons, but it did not differ among islands. Bots were found during all the 12 calendar months, suggesting a multivoltine reproductive schedule. Although bot activity varied seasonally, there was little synchrony of bot activity among islands. Bot density was related negatively to rainfall but was not related to host density, suggesting that drier ambient conditions may promote reproduction by adult bot flies in this system.