Immunogenicity of subcutaneous TNF inhibitors and its clinical significance in real-life setting in patients with spondyloarthritis.

KEY MESSAGES: Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1-2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients.

Social Network Organization, Structure, and Patterns of Influence Within a Community of Transgender Women in Lima, Peru: Implications for Biomedical HIV Prevention.

Understanding social network structures can contribute to the introduction of new HIV prevention strategies with socially marginalized populations like transgender women (TW). We conducted 20 semi-structured interviews and four focus groups (n = 32) with TW from selected social networks in Lima, Peru between May and July, 2015. Participants described layers of social influence from diverse actors in their social networks. The majority identified a close relative as their primary social support, with whom they confided secrets but avoided issues of transgender identity, sexuality, and sex work. Participants described close circles of TW friends with whom they shared information about gender identity, body modification, and sexual partners, but avoided issues like HIV. Community leadership included political leaders (who advocated for transgender rights) as well as social leaders (who introduced TW to hormone therapy, body modification, and commercial sex). Detailed analysis of TW social networks can contribute to implementation and acceptability of new HIV prevention technologies.

Evaluation of an Online Educational Program for Parents and Caregivers of Children With Food Allergies.

BACKGROUND AND OBJECTIVE: The increasing prevalence of food allergy affects both patients and their families. Objective: The aim of this study was to evaluate the impact of an online educational program designed for parents and caregivers of children with food allergies. The program was developed by a multidisciplinary group comprising health care professionals, researchers, and expert patients under the participatory medicine model. MATERIAL AND METHODS: Participants took a 2-week online educational program covering major topics in food allergy management. General knowledge about the disease, symptoms, treatment, and topics relevant to families' daily lives were evaluated. The contents included educational videos, online forums, and live video chats. A pretest/posttest questionnaire survey was used to evaluate the impact of the program. RESULTS: A total of 207 participants enrolled in the educational program, which was completed by 130 (62.8%). Knowledge acquisition improved significantly following participation in the program in 15 out of 30 items (50%), reaching P<.001 for 8 items (26.7%). Of the 207 participants who started the program, 139 (67.1%) visited online forums, and 27.5% attended video chats. Average overall satisfaction with the educational program was 8.78 (on a scale of 0 to 10). CONCLUSIONS: The results obtained show that parents improved their knowledge in all areas of food allergy. The high level of satisfaction among participants suggests that digital learning tools are effective and motivational, enabling patients to acquire appropriate knowledge and thus increasing their quality of life.

Evaluation of an educational programme with workshops for families of children with food allergies.

BACKGROUND: When a child is diagnosed with a food allergy, prevention and patient education are the key interventions for maintaining the child's health and quality of life and that of his or her whole family. However, health education activities for the families of children with food allergies are very limited, and most of these activities have not been evaluated. Therefore, the objectives of the present study were to develop an educational programme, to empower its participants through workshops, and to evaluate its results. METHODS: Several types of educational materials were created specifically for the programme, called "Proyecto CESA" ("STOP-FAR Project: Stop Food-Induced Allergic Reactions"). The programme was carried out in seven Spanish cities and was attended by parents and caregivers. The workshops were led by physicians specialising in allergies and by expert patients. Afterwards, participant learning and satisfaction were evaluated based on questionnaires that were completed both before and after the workshops. RESULTS: A significant improvement was observed in 29 items out of 40 (McNemar's test). Participant satisfaction with the programme was also very high: 90% rated the course between 8 and 10 points out of a possible 10 (41% rated it as a 10). CONCLUSION: The face-to-face workshops, which included utilisation of educational materials, had positive results in terms of learning as well as in levels of satisfaction in participating families.

Sampling methodologies for epidemiologic surveillance of men who have sex with men and transgender women in Latin America: an empiric comparison of convenience sampling, time space sampling, and respondent driven sampling.

Alternatives to convenience sampling (CS) are needed for HIV/STI surveillance of most-at-risk populations in Latin America. We compared CS, time space sampling (TSS), and respondent driven sampling (RDS) for recruitment of men who have sex with men (MSM) and transgender women (TW) in Lima, Peru. During concurrent 60-day periods from June-August, 2011, we recruited MSM/TW for epidemiologic surveillance using CS, TSS, and RDS. A total of 748 participants were recruited through CS, 233 through TSS, and 127 through RDS. The TSS sample included the largest proportion of TW (30.7 %) and the lowest percentage of subjects who had previously participated in HIV/STI research (14.9 %). The prevalence of newly diagnosed HIV infection, according to participants' self-reported previous HIV diagnosis, was highest among TSS recruits (17.9 %) compared with RDS (12.6 %) and CS (10.2 %). TSS identified diverse populations of MSM/TW with higher prevalences of HIV/STIs not accessed by other methods.

[Carpal tunnel compression syndrome and third finger in trigger secondary to an encapsulated fibrolipoma of the wrist: a case report]. / Síndrome de compresión del túnel del carpo y tercer dedo en gatillo secundarios a un fibrolipoma encapsulado de la muñeca: reporte de un caso.

INTRODUCTION: the association of carpal tunnel syndrome with stenosing tenosynovitis of the hand is very rare, even more, if it is generated by a fibrolipoma at the carpal tunnel. The imaging study useful to detect this type of hand injuries are X-ray screening for carpal tunnel, computed tomography and magnetic resonance imaging. But these are not commonly used for the study of protocolized carpal tunnel syndrome and much less trigger finger. OBJECTIVE: the aim of this work is to report a case of a middle-aged female with carpal tunnel syndrome characteristic symptoms, associated with the third trigger finger; she was handled with the release of the median nerve by a minimally invasive approach, in addition to the A1 pulley release. CLINICAL CASE: the patient persists with both problems and at a secondary surgical review, we detected wrist locking sensation. The patient was reoperated finding an ovoid encapsulated tumor, measuring 3.0 × 2.0 × 1.0 cm, with smooth outer surface, whitish appearance, and soft rubbery consistency. The biopsy pathology outlines identified an encapsulated fibrolipoma, causing nerve compression and locking flexor tendon. CONCLUSION: the importance of this writing is in adding tumors to the etiological repertoire, which can cause compression of the median nerve and even less frequent as a cause of the flexor tendons of the hand snagging.

INTRODUCCIÓN: la asociación del síndrome del túnel del carpo con tenosinovitis estenosante de la mano es muy rara, aún más, si es generada por un fibrolipoma a nivel del túnel del carpo. El estudio de imagen para detectar este tipo de lesiones en la mano incluye: desde una radiografía con proyección para el túnel del carpo, tomografía axial computarizada y resonancia magnética nuclear; pero éstos no se utilizan habitualmente para el estudio protocolizado del síndrome del túnel del carpo y mucho menos para los dedos en gatillo. OBJETIVO: el objetivo de este trabajo es reportar un caso en el cual se presenta la sintomatología característica de un síndrome de túnel del carpo, asociada a tercer dedo en gatillo, el cual se maneja con la liberación del nervio mediano por medio de un abordaje de mínima invasión, además de la polea A1. CASO CLÍNICO: la paciente persistió con ambas alteraciones y en la revisión secundaria se detectó bloqueo a nivel de la muñeca. Se intervino nuevamente a la paciente y se encontró una tumoración encapsulada, que midió 3.0 × 2.0 × 1.0 cm, con superficie externa lisa, blanquecina, de aspecto ovoide y consistencia blanda "ahulada". El estudio anatomopatológico la identificó como un fibrolipoma encapsulado que ocasionó la compresión nerviosa y el bloqueo del tendón flexor. CONCLUSIÓN: la importancia de este reporte de caso radica en agregar los tumores al repertorio etiológico, que además pueden provocar una compresión del nervio mediano y en que sean aún menos frecuentes como causa de atrapamiento de los tendones flexores de la mano.

Computer graphic display method for visualizing three-dimensional biological structures.

A computer graphic display method that produces two-dimensional perspective views of three-dimensional objects is presented. The method is applied to the reconstruction at a resolution of 2.2 nanometers of the neck of bacteriophage phi 29, obtained from transmission electron micrographs processed by the direct Fourier method. The combined use of directed illumination, reflectance models, color, and different levels of transparency provides a powerful tool for a better interpretation of the three-dimensional structure, allowing improved correlation with genetic, structural, and biochemical data.

Síndrome de compresión del túnel del carpo y tercer dedo en gatillo secundarios a un fibrolipoma encapsulado de la muñeca: reporte de un caso / Carpal tunnel compression syndrome and third finger in trigger secondary to an encapsulated fibrolipoma of the wrist: a case report

Resumen: Introducción: la asociación del síndrome del túnel del carpo con tenosinovitis estenosante de la mano es muy rara, aún más, si es generada por un fibrolipoma a nivel del túnel del carpo. El estudio de imagen para detectar este tipo de lesiones en la mano incluye: desde una radiografía con proyección para el túnel del carpo, tomografía axial computarizada y resonancia magnética nuclear; pero éstos no se utilizan habitualmente para el estudio protocolizado del síndrome del túnel del carpo y mucho menos para los dedos en gatillo. Objetivo: el objetivo de este trabajo es reportar un caso en el cual se presenta la sintomatología característica de un síndrome de túnel del carpo, asociada a tercer dedo en gatillo, el cual se maneja con la liberación del nervio mediano por medio de un abordaje de mínima invasión, además de la polea A1. Caso clínico: la paciente persistió con ambas alteraciones y en la revisión secundaria se detectó bloqueo a nivel de la muñeca. Se intervino nuevamente a la paciente y se encontró una tumoración encapsulada, que midió 3.0 × 2.0 × 1.0 cm, con superficie externa lisa, blanquecina, de aspecto ovoide y consistencia blanda «ahulada¼. El estudio anatomopatológico la identificó como un fibrolipoma encapsulado que ocasionó la compresión nerviosa y el bloqueo del tendón flexor. Conclusión: la importancia de este reporte de caso radica en agregar los tumores al repertorio etiológico, que además pueden provocar una compresión del nervio mediano y en que sean aún menos frecuentes como causa de atrapamiento de los tendones flexores de la mano.

Abstract: Introduction: the association of carpal tunnel syndrome with stenosing tenosynovitis of the hand is very rare, even more, if it is generated by a fibrolipoma at the carpal tunnel. The imaging study useful to detect this type of hand injuries are X-ray screening for carpal tunnel, computed tomography and magnetic resonance imaging. But these are not commonly used for the study of protocolized carpal tunnel syndrome and much less trigger finger. Objective: the aim of this work is to report a case of a middle-aged female with carpal tunnel syndrome characteristic symptoms, associated with the third trigger finger; she was handled with the release of the median nerve by a minimally invasive approach, in addition to the A1 pulley release. Clinical case: the patient persists with both problems and at a secondary surgical review, we detected wrist locking sensation. The patient was reoperated finding an ovoid encapsulated tumor, measuring 3.0 × 2.0 × 1.0 cm, with smooth outer surface, whitish appearance, and soft rubbery consistency. The biopsy pathology outlines identified an encapsulated fibrolipoma, causing nerve compression and locking flexor tendon. Conclusion: the importance of this writing is in adding tumors to the etiological repertoire, which can cause compression of the median nerve and even less frequent as a cause of the flexor tendons of the hand snagging.

Three-dimensional reconstruction of bacteriophage phi 29 neck particles at 2 X 2 nm resolution.

The three-dimensional structure of the head-to-tail connecting region of bacteriophage phi 29 has been studied by analysing two-dimensional, hexagonal ordered aggregates of negatively stained viral necks to a resolution of 2 X 2 nm. These necks are composed of two proteins, p10 and p11; p10 being the connector protein. A 12-folded and a 6-folded axially symmetric domain are present in the specimen. The 12-folded domain is the larger part of the structure; it consists of 12 subunits associated in pairs. These subunits appear to be more closely paired towards the centre, where only six subunits are resolved forming the 6-folded domain. The pairs of subunits present an important twist between the 12-folded and the 6-folded areas. A conical hole is formed at the centre of the structure. This hole is more open at the 12-folded domain than at the level of the possible zone of interaction between p10 and p11, where it is almost closed. Protein p11 is very poorly represented in the reconstruction, probably due to lack of staining. The structure described for the phi 29 neck has many of the attributes expected for an active device involved in bacteriophage DNA encapsidation.

Genetic susceptibility to gastric cancer.

Although the incidence and mortality rates of gastric cancer not located in the cardia have been decreasing in the last decades, it still remains the second most common cancer in the world. On the other hand, adenocarcinoma of the cardia and gastroesophageal junction has been rapidly rising in many populations over the past two decades.

Implementation effects of GFATM-supported HIV/AIDS projects on the health sector, civil society and affected communities in Peru 2004-2007.

The emergence of opportunities for support from the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) for HIV-related projects has so far generated funding of over US$75 million for three proposals in Peru. The size of this investment creates the need for close monitoring to ensure a reasonable impact. This paper describes the effects of collaboration with the GFATM on key actors involved in HIV-related activities and on decision-making processes; on health sector divisions; on policies and sources of financing; on equity of access; and on stigma and discrimination of vulnerable and affected populations. Data analysed included primary data collected through interviews with key informants, in-depth interviews and group discussions with vulnerable and affected populations, as well as several public documents. Multisectorality, encouraged by the GFATM, is incipient; centralist proposals with limited consultation, a lack of consensus and short preparation times prevail. No accountability mechanisms operate at the Country Coordinating Mechanism (CCM) level regarding CCM members or society as a whole. GFATM-funded activities have required significant input from the public sector, sometimes beyond the capacity of its human resources. A significant increase in HIV funding, in absolute amounts and in fractions of the total budget, has been observed from several sources including the National Treasury, and it is unclear whether this has implied reductions in the budget for other priorities. Patterns of social exclusion of people living with HIV/AIDS are diverse: children and women are more valued; while transgender persons and sex workers are often excluded.

[Fundamental bases of nuclear cardiology]. / Las bases fundamentales de la cardiología nuclear.

Nuclear cardiology the clinical speciality that deals with the acquisition of biochemical and functional data through the external detection of electromagnetic radiations emitted by internally administered radiotracers. The most important concepts in the development of this new technology are reviewed: the radiotracers, the nuclear instrumentation, and the systems for data processing and analysis. It is included a comparison between the radiation doses delivered by nuclear cardiology studies and by diagnostic x-ray procedures, common in cardiology. It is concluded with a vision to the near future: radioimmunoscintigraphy, use of biochemical cell receptors, metabolic studies by positrom emmision tomography, and the revolutionary technology of tomography by nuclear magnetic resonance.

Digital restoration models for color imaging.

Color images degraded by defocusing and chromatism are restored using different digital models and linear filtering techniques. The restoration process for color images is properly performed through the filters associated with three transfer functions for tristimulus values. However, the use of three monochromatic OTFs corresponding to the maxima of the color receiver is also discussed for different cases of wavelengthdependent aberrations, since it enables a significant reduction in the computer processing time.

Modification of rat plasma lipoproteins induced by acute immobilization stress.

To determine the influence of acute stress on plasma lipids and lipoproteins, 66 Wistar rats (31 males and 35 females) were immobilized for 10 hours. Previously, these animals were deprived of food for another 10 hours. Because immobilization involves forced fasting, the control group consisted of 58 rats (30 males and 28 females) that fasted for 20 hours. The immobilized animals showed gastric lesions (94% of the males and 83% of the females). Plasma lipoproteins were separated by ultracentrifugation in the following densities: less than 1.006 g/ml (very low-density lipoproteins (VLDL)), 1.006 to 1.040 g/ml (low-density lipoproteins (LDL)), 1.040 to 1.063 g/ml (high-density lipoproteins fraction 1 (HDL1)), and 1.063 to 1.210 g/ml (HDL2). Measurements were adjusted according to hematocrit value. In male rats, immobilization caused a rise in total plasma cholesterol as a consequence of increases in the VLDL, LDL, and HDL1 fractions. In female rats, however, no significant variations were observed in plasma cholesterol, although there was a slight, but significant, increase in VLDL and LDL cholesterol. Immobilization caused hypertriglyceridemia in both sexes as a result of an increase in triglycerides in all classes of lipoproteins, except in HDL2 in both sexes and VLDL in males. Finally, the protein content of VLDL and LDL increased both in male and female rats; HDL2 levels decreased in female rats. These changes suggest an atherogenic character of stress caused by continuous immobilization during 10 hours.

Tumor-dependent activation of rodent hepatic stellate cells during experimental melanoma metastasis.

In this work we report the presence of intrametastatic smooth-muscle iso-alpha-actin (SMA)-expressing cells which appeared from the early stages of the hepatic metastasis process of intrasplenically injected B16 melanoma (B16M) cells. They formed a network of stromal cells among B16M cells, a very low percentage of them expressing desmin. In contrast, those parts of liver tissue unaffected by metastasis had perisinusoidal desmin-expressing quiescent hepatic stellate cells (qHSC) which did not express SMA. Exposure of freshly isolated rat quiescent hepatic stellate cells (qHSC) to B16M cell-conditioned medium (B16M-CM) leads to a progressive increase (P < .01) in the number of SMA-expressing cells, which was accompanied by a parallel reduction in the number of desmin-expressing cells. In addition, B16M-CM also contained chemotactic factor(s) which significantly (P < .01) increased (50%) in vitro qHSC migration and stimulated both [3H]thymidine and [3H]glucosamine uptake in qHSC. Moreover, B16M-CM also significantly (P < .01) enhanced qHSC secretion of matrix metalloproteinase-2 (MMP-2), and unknown chemotactic factor(s) enhancing in vitro migration of B16M cells. The results suggest that B16 melanoma releases qHSC-activating factors, which induce the appearance of metastasis-infiltrating myofibroblasts by a paracrine mechanism. Such cells showed cytoskeletal alterations which are associated with enhanced proliferation, glycosaminoglycan synthesis, MMP-2 secretion, and tumor-chemotactic factor production. Thus, tumor-activated qHSC may play an important role in melanoma cell motility and invasion during hepatic metastasis progression.

Structure of phage phi 29 connector protein assembled in vivo.

The protein p10 that forms the connector of phage phi 29, has been produced in Escherichia coli harboring a plasmid that carried the gene coding for this protein. The connector protein is assembled in a 13.4-S oligomer that has an apparent molecular weight of 460,000, suggesting that it is a dodecamer. The purified oligomers have been studied by electron microscopy of the isolated particles as well as by image-processing techniques (Fourier and rotational filtering) of artificially induced two-dimensional aggregates. The results show that the purified p10 is assembled in a circular structure with a hole in its center and 12 morphological units in the periphery. Both the morphology and the dimensions of this p10 oligomer are very similar to those of the upper neck collar extracted from phi 29 viral particles. The results strongly suggest the close relationship between the p10 oligomers assembled in E. coli and the ones produced in phi 29 infected Bacillis subtilis.