Trends in proportion of older HIV-infected people in care in Latin America and the Caribbean: a growing challenge.

We aimed to quantify the proportion of people receiving care for HIV-infection that are 50 years or older (older HIV patients) in Latin America and the Caribbean between 2000 and 2015 and to estimate the contribution to the growth of this population of people enrolled before (<50yo) and after 50 years old (yo) (⩾50yo). We used a series of repeated, cross-sectional measurements over time in the Caribbean, Central and South American network (CCASAnet) cohort. We estimated the percentage of patients retained in care each year that were older HIV patients. For every calendar year, we divided patients into two groups: those who enrolled before age 50 and after age 50. We used logistic regression models to estimate the change in the proportion of older HIV patients between 2000 and 2015. The percentage of CCASAnet HIV patients over 50 years had a threefold increase (8% to 24%) between 2000 and 2015. Most of the growth of this population can be explained by the increasing proportion of people that enrolled before 50 years and aged in care. These changes will impact needs of care for people living with HIV, due to multiple comorbidities and high risk of disability associated with aging.

Caffeine and headache: specific remarks. / Cafeína y cefalea: consideraciones especiales.

Caffeine is the most widely used psychostimulant worldwide. Excessive caffeine consumption induces a series of both acute and chronic biological and physiological changes that may give rise to cognitive decline, depression, fatigue, insomnia, cardiovascular changes, and headache. Chronic consumption of caffeine promotes a pro-nociceptive state of cortical hyperexcitability that can intensify a primary headache or trigger a headache due to excessive analgesic use. This review offers an in-depth analysis of the physiological mechanisms of caffeine and its relationship with headache.

3D printed dielectric rectangular waveguides, splitters and couplers for 120 GHz.

We use a 3D printer to fabricate rectangular dielectric single mode waveguides for 120 GHz. The rectangular waveguides consisting of polystyrene showed an attenuation of 6.3 dB/m, which is low enough for short devices. We also characterize 3D printed Y-splitters and a 1x3-splitter based on multimode interference. Further, we construct and measure a variable planar waveguide coupler which can be used as a 3-dB coupler, a cross-coupler and no coupler at all.

Demographic and social profile of epilepsy in a vulnerable low-income population in Bogotá, Colombia. / Perfil demográfico y social de la epilepsia en una población vulnerable y de bajos recursos económicos en Bogotá, Colombia.

INTRODUCTION: Very few studies describe the demographic and social profile of epilepsy in vulnerable low-income populations. METHODS: Observational, descriptive, cross-sectional study prospectively recording data from all patients diagnosed with epilepsy who attended a specialist neurology consultation between January and March 2014. Data were analysed using descriptive epidemiology tools. RESULTS: A total of 107 patients were evaluated, of whom 24.2% were illiterate and only 10.2% had completed a higher education programme. Most of the patients (86.8%) had a low socioeconomic status; 73.8% were single and 76.7% were unemployed. The main risk factors for epilepsy in this population were recorded as follows: delayed psychomotor development (n=24, 22.4%), head trauma (n=16, 14.9%), and central nervous system infection (n=13, 12.1%). Most patients (70.1%) responded to antiepileptic drugs (controlled cases) and 15.4% (n=15) had drug-resistant epilepsy (refractory cases). CONCLUSION: The demographic and clinical profiles of the patients included in this study resemble those published for high-income populations; differences are mostly limited to aetiological classification and risk factors. The social profile of the patients evaluated in this study shows high rates of unemployment, illiteracy, and single marital status. These findings seem to be more frequent and prevalent in this group than in high income populations.

Role of main neuroendocrine pathways activated by swim stress on mast cell-dependent peritoneal TNF production after LPS administration in mice.

OBJECTIVE AND DESIGN: To characterize the effects of swim stress on the early mast cell (MC)-dependent peritoneal production of TNF in response to lipopolysaccharide (LPS) administration in mice, identifying the neuroendocrine mediators involved. SUBJECTS: Ten to twelve-week-old Swiss Webster, C57BL/6 J or c-Kit (Wsh/Wsh) mice were used. TREATMENT: Animals were intraperitoneally challenged with LPS at different times after forced swimming (FS) and peak TNF production was determined in peritoneal washes at optimal time after LPS administration. Selective blockage of main neuroendocrine pathways was performed before swim stress. METHODS: TNF concentrations were determined by ELISA. RESULTS: FS provoked an immediate and transient inhibition of LPS-elicited, MC-dependent TNF accumulation in peritoneum, which lasted around 30 min. Suppresive effects of FS were absent on MC-deficient c-Kit (Wsh/Wsh) mice but were recovered after reconstitution with MC. Adrenalectomy or DSP4 administration increased basal ip TNF levels and enhanced LPS-induced TNF release without any effect on stress-induced inhibitory effects, mifepristone did not produce any change on stress-induced inhibition, whereas mecamylamine administration increased basals and attenuated stress effects. CONCLUSIONS: Swim stress transiently inhibits the canonical MC-dependent response of TNF production in response to LPS in murine peritoneal cavity with the main participation of the cholinergic anti-inflammatory reflex.

Torsion profiling of proteins using magnetic particles.

We report a method to profile the torsional spring properties of proteins as a function of the angle of rotation. The torque is applied by superparamagnetic particles and has been calibrated while taking account of the magnetization dynamics of the particles. We record and compare the torsional profiles of single Protein G-Immunoglobulin G (IgG) and IgG-IgG complexes, sandwiched between a substrate and a superparamagnetic particle, for torques in the range between 0.5 × 10(3) and 5 × 10(3) pN·nm. Both molecular systems show torsional stiffening for increasing rotation angle, but the elastic and inelastic torsion stiffnesses are remarkably different. We interpret the results in terms of the structural properties of the molecules. The torsion profiling technique opens new dimensions for research on biomolecular characterization and for research on bio-nanomechanical structure-function relationships.

Prevalence of Plasmid-Associated Tetracycline Resistance Genes in Multidrug-Resistant Escherichia coli Strains Isolated from Environmental, Animal and Human Samples in Panama.

Antimicrobial resistance bacteria are nowadays ubiquitous. Its presence has been reported in almost every type of source, from water for agricultural and recreative use, water distribution pipes, and wastewater, to food, fomites, and clinical samples. Enterobacteriaceae, especially Escherichia coli, are not the exception, showing an increased resistance to several antibiotics, causing a global health and economic burden. Therefore, the monitoring of fecal microbiota is important because it is present in numerous reservoirs where gene transfer between commensal and virulent bacteria can take place, representing a potential source of resistant E. coli. In this work, antibiotic resistance profiles of 150 E. coli isolates from environmental, animal, and human samples, collected in three rural areas in Panama, were analyzed. A total of 116 isolates were resistant to at least one of the nine antibiotics tested. Remarkably, almost 100% of these exhibited resistance to tetracycline. Plasmid-associated tetA and tetB genes were detected in 42.86% of the isolates analyzed, tetA being the most prevalent. These results suggest that tetracycline resistance would be used as a convenient indicator of genetic horizontal transfer within a community.

Skeletal Muscle Mass by Bioelectrical Impedance Analysis and Calf Circumference for Sarcopenia Diagnosis.

Skeletal muscle mass (SMM) plays an important role in health and physical performance. Its estimation is critical for the early detection of sarcopenia, a disease with high prevalence and high health costs. While multiple methods exist for estimating this body component, anthropometry and bioelectrical impedance analysis (BIA) are the most widely available in low- to middle-income countries. This study aimed to determine the correlation between muscle mass, estimated by anthropometry through measurement of calf circumference (CC) and skeletal mass index (SMI) by BIA. This was a cross-sectional and observational study that included 213 functional adults over 65 years of age living in the community. Measurements of height, weight, CC, and SMM estimated by BIA were made after the informed consent was signed. 124 women mean age 69.6 ± 3.1 years and 86 men mean age 69.5 ± 2.9 years had the complete data and were included in the analysis. A significant positive moderate correlation among CC and SMI measured by BIA was found (Pearson r= 0.57 and 0.60 for women and men respectively (p=0.0001)). A moderate significant correlation was found between the estimation of SMM by CC and by BIA. This suggests that CC could be used as a marker of sarcopenia for older adults in settings in lower-middle-income countries where no other methods of diagnosing muscle mass are available. Although the CC is not the unique parameter to the diagnosis of sarcopenia, it could be a useful procedure in the clinic to identify patients at risk of sarcopenia.

Longitudinal, lateral, vertical and temporal thermal heterogeneity in a large impounded river: implications for cold-water refuges.

Dam operations can affect mixing of the water column thereby influencing thermal heterogeneity spatially and temporally. This occurs by restricting or eliminating connectivity in longitudinal, lateral, vertical and temporal dimensions. We examined thermal heterogeneity across space and time and identified potential cold-water refuges for salmonids in a large impounded river in inland northwestern USA. To describe these patterns, we used thermal infrared (TIR) imagery, in situ thermographs, and high-resolution 3-D hydraulic mapping. We explained the median water temperature and probability of occurrence of cool-water areas using generalized additive models (GAMs) at reach and sub-catchment scales, and we evaluated potential cold-water refuge occurrence in relation to these patterns. We demonstrated that (1) lateral contributions from tributaries dominated thermal heterogeneity; (2) thermal variability at confluences was approximately an order of magnitude greater than of the main stem; (3) potential cold-water refuges were mostly found at confluences; and (4) the probability of occurrence of cool areas and median water temperature were associated with channel geomorphology and distance from dam. These findings highlight the importance of using multiple approaches to describe thermal heterogeneity in large impounded rivers and the need to incorporate these types of rivers in the understanding of thermal riverscapes because of their limited representation in the literature.

HIV-related tuberculosis: mortality risk in persons without vs. with culture-confirmed disease.

BACKGROUND: Tuberculosis (TB) diagnosis in human immunodeficiency virus (HIV) positive persons is difficult, particularly in resource-limited settings. The relationship between TB culture status and mortality in HIV-positive persons treated for TB is unclear. METHODS: We evaluated HIV-positive adults treated for TB at or after their first HIV clinic visit in Argentina, Brazil, Chile, Honduras, Mexico or Peru from 2000 to 2015. Anti-tuberculosis treatment included 2 months of isoniazid, rifampicin (RMP)/rifabutin (RBT), pyrazinamide ± ethambutol, followed by continuation phase treatment with isoniazid + RMP/RBT. RESULTS: Of 759 TB-HIV patients, 238 (31%) were culture-negative, 228 (30%) had unknown culture status or did not undergo culture and 293 (39%) were culture-positive. The median CD4 at TB diagnosis was 96 (interquartile range 40-228); 636 (84%) received concurrent antiretroviral therapy (ART) and anti-tuberculosis treatment. There were 123 (16%) deaths: 90/466 (19%) with TB culture-negative, unknown or not performed vs. 33/293 (11%) who were TB culture-positive (P = 0.005). In Kaplan-Meier analysis, mortality in TB patients without culture-confirmed disease was higher (P = 0.002). In a Cox model adjusted for age, sex, CD4, ART timing, disease site and stratified by study site, mortality in persons without culture-confirmed TB was not significantly increased compared to those with culture-positive TB (hazard ratio 1.39, 95%CI 0.89-2.16, P = 0.15). CONCLUSION: Most HIV-positive patients treated for TB did not have culture-confirmed TB, and mortality tended to be higher in patients without culture-confirmed disease, although the association was not statistically different after adjusting for other variables. Accurate TB diagnosis in HIV-positive persons is crucial.

Stimulation of nAchRα7 Receptor Inhibits TNF Synthesis and Secretion in Response to LPS Treatment of Mast Cells by Targeting ERK1/2 and TACE Activation.

The cholinergic anti-inflammatory pathway is recognized as one of the main mechanisms of neuromodulation of the immune system. Activation of the α7 nicotinic acetylcholine receptor (nAchRα7) suppresses cytokine synthesis in distinct immune cells but the molecular mechanisms behind this effect remain to be fully described. Mast cells (MCs) are essential players of allergic reactions and innate immunity responses related to chronic inflammation. Activation of TLR4 receptor in MCs leads to the rapid secretion of pre-synthesized TNF from intracellular pools and to the activation of NFκB, necessary for de novo synthesis of TNF and other cytokines. Here we report that the nAchRα7 receptor specific agonist GTS-21 inhibits TLR4-induced secretion of preformed TNF from MCs in vivo and in vitro. Utilizing bone marrow-derived mast cells (BMMCs) it was found that GTS-21 also diminished secretion of de novo synthesized TNF, TNF mRNA accumulation and IKK-dependent p65-NFκB phosphorylation in response to LPS. nAchRα7 triggering prevented TLR4-induced ERK1/2 phosphorylation, which resulted an essential step for TNF secretion due to the phosphorylation of the metallopeptidase responsible for TNF maturation (TACE). Main inhibitory actions of GTS-21 were prevented by AG490, an inhibitor of JAK-2 kinase. Our results show for the first time, that besides the prevention of NFκB-dependent transcription, inhibitory actions of nAchRα7 triggering include the blockade of pathways leading to exocytosis of granule-stored cytokines in MCs.

[Calcitonin gene-related peptide: a key player neuropeptide in migraine]. / Peptido relacionado con el gen de la calcitonina: un neuropeptido clave en la migraña.

Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide produced as a consequence of alternative RNA processing of the calcitonin gene. CGRP is widely distributed in the nervous system, particularly at anatomical areas thought to be involved with migraine pathophysiology, including the trigeminovascular nociceptive system. Over the past two decades, a convergence of basic and clinical evidence has established the CGRP as a key player in migraine. CGRP enhances sensitivity to sensory input at multiple levels in both the periphery and central nervous system. Within the brain, the wide distribution of CGRP and CGRP receptors provides numerous possible targets for CGRP to act as a neuromodulator. Now, CGRP has emerged as a promising therapeutic target for a number of novel treatments for migraine. This review discusses the evidence behind the role of CGRP in migraine and the state of CGRP-based mechanism treatment development.

TITLE: Peptido relacionado con el gen de la calcitonina: un neuropeptido clave en la migraña.El peptido relacionado con el gen de la calcitonina (CGRP) es un neuropeptido multifuncional producido por el empalme alternativo del gen de la calcitonina. El CGRP esta ampliamente distribuido en el sistema nervioso, particularmente en estructuras anatomicas posiblemente implicadas en la fisiopatologia de la migraña, incluyendo el sistema trigeminovascular. En las ultimas dos decadas, el conjunto de datos de estudios clinicos y de ciencias basicas ha establecido el papel fundamental del CGRP en migraña. El CGRP aumenta la sensibilidad a los estimulos sensoriales en multiples niveles, tanto en el sistema nervioso periferico como en el central. En el cerebro, la amplia distribucion del CGRP y de sus receptores indica varios sitios posibles en los cuales este peptido actua como neuromodulador. En la actualidad, el CGRP ha surgido como un objetivo terapeutico para nuevos tratamientos en la migraña. El objetivo de la revision es exponer la evidencia detras del papel del CGRP en la migraña y el estado actual de las nuevas alternativas terapeuticas basadas en el CGRP.

The shape of dementia: new measures of morphological complexity in event-related potentials (ERP) and its application to the detection of Alzheimer's disease.

In this paper, we address the problem of quantifying the commonly observed disorganization of the stereotyped wave form of the ERP associated with the P300 component in patients with Alzheimer's disease. To that extent, we propose two new measures of complexity which relate the spectral content of the signal with its temporal waveform: the spectral matching coefficient and the spectral matching entropy. We show by means of experiments that those measures effectively measure complexity and are related to the shape in an intuitive way. Those indexes are compared with commonly used measures of complexity when comparing AD patients against age-matched healthy controls. The results indicate that AD ERP signals are, indeed, more complex in the shape than that of controls, and this result is evidenced mainly by means of our new measures which have a better performance compared to similar ones. Finally, we try to explain this increase in complexity in light of the communication through coherence hypothesis framework, relating commonly found changes in the EEG with our own results.

Surfactants modify the torsion properties of proteins: a single molecule study.

Surfactants are widely used in diagnostic assays to prevent protein aggregation and non-specific adsorption at surfaces. Here, a single molecule magnetic torque tweezers study is reported, aiming to quantify surfactant-induced changes in the torsional flexibility of a protein model system: protein-G-immunoglobulin G (IgG) attached to a glass surface. The influences of Sodium Dodecyl Sulphate (SDS) and Polysorbate 20 (Tween 20) on the protein pair have been investigated. The proteins were exposed to the surfactants at concentrations relative to the Critical Micelle Concentration (CMC), namely 0.1× CMC, 1× CMC and 10× CMC. Both surfactants increase the torsional flexibility of the protein-G-IgG complex. Tween 20 is most effective at increasing the torsional flexibility of the complex at the surface while SDS is more effective at dissociating the protein bonds. Tweezer data on the IgG-IgG protein pair show no influence of Tween 20 on the torsional flexibility. Furthermore, temperature dependent near-UV and far-UV Circular Dichroism (CD) data at 10× CMC show that Tween 20 does not significantly alter the secondary and tertiary structure of both protein-G and IgG while SDS does. These results provide evidence that both the mechanical properties of the protein structure and the interaction between proteins can alter the torsional rigidity measured with magnetic torque tweezers. This study shows for the first time the ability to use magnetic torque tweezers as a probe for surfactant-induced changes in proteins at a single molecule level.

Experiencia en el tratamiento del carcinoma basocelular localmente avanzado o metastásico con Vismodegib en el instituto nacional de cancerología entre los años 2014 y 2015 / Treatment of locally advanced or metastatic basal cell carcinoma with Vismodegib: Experience at the national Institute of Cancerology during 2014 -2015

RESUMEN Introducción: El carcinoma basocelular es el cáncer de piel más frecuente, y en su patogenía se ha descrito la activación de la vía Hedgehog. El Vismodegib, un inhibidor selectivo de esta vía ha demostrado ser efectivo en el tratamiento de la enfermedad localmente avanzada irresecable o metastásica. El presente estudio describe la respuesta clínica al tratamiento con Vismodegib en una población de Colombia. Materiales y métodos: Presentamos una serie de casos entre enero de 2014-noviembre de 2015 del Instituto Nacional de Cancerología (Bogotá Colombia). El tratamiento establecido fue Vismodegib (cápsulas de 150 mg vía oral diario), en ciclos cada 28 días hasta progresión o toxicidad limitante. El análisis estadístico se basó en el cálculo de proporciones en variables cualitativas, medidas de tendencia central y dispersión para las cuantitativas. Se realizó análisis de supervivencia descriptiva (Kaplan-Meier). El análisis estadístico se realizó por el software estadístico STATA 11.0. Resultados: 33 pacientes fueron incluidos, de los cuales el 73% recibieron al menos 3 ciclos de tratamiento. De estos el 63,6% tuvieron respuesta parcial y el 12,1% presentaron respuesta completa. La media de supervivencia global y libre de progresión fue de 21,7 meses (IC 95% 18,9 a 24,4 meses) y 22,3 meses (IC 95% 20,6 a 23,9 meses), respectivamente. Los eventos adversos más frecuentes fueron: espasmos musculares (35,2%), disgeusia (24,7%) y alopecia (15%). Conclusiones: En esta serie de casos, a pesar de las irregularidades en el inicio y continuidad del manejo con Vismodegib, se obtuvieron tasas de respuesta similares a las previamente descritas.

Abstract Introduction: Basal cell carcinoma is the most frequent skin cancer, and the activation of the Hedgehog pathway has been described in its pathogenesis. Vismodegib is a selective inhibitor of this pathway, that has shown to be effective in the treatment of locally unresectable or metastatic advanced disease. The present study describes the clinical response to treatment with vismodegib in a Colombian population. Methods: We present a case series, carried out between January 2014 and November 2015 at the National Institute of Cancerology (Bogotá, Colombia). The established treatment was Vismodegib (capsules of 150 mg orally daily), in cycles every 28 days until progression or limiting toxicity. The statistical analysis was based on the calculation of proportions in qualitative variables, measures of central tendency and dispersion for quantitative ones. Descriptive survival analysis (Kaplan-Meier) was performed. The statistical analysis was performed by the statistical software STATA 11.0. Results: 33 patients were included, of which 73% received at least 3 treatment cycles. Of these, 63.6% had a partial response and 12.1% had a complete response. The mean of progression-free and overall survival was 21.7 months (95% CI 18.9 to 24.4 months) and 22.3 months (95% CI 20.6 to 23.9 months), respectively. The most frequent adverse events were: muscle spasms (35.2%), dysgeusia (24.7%) and alopecia (15%). Conclusion: In this series of cases, despite the irregularities in the initiation and continuity of management with Vismodegib, response rates were similar to those described in the literature.

Fetal mortality in sibships with one or more affected members with oral clefts.

We investigated the fetal mortality in 903 sibships with at least one member having cleft lip with or without cleft palate [CL(P)] and 213 with at least one individual affected with cleft palate (CP) derived from three different data sources in México. The frequency of fetal wastage (abortion and/or stillbirth) was not increased in sibships where the propositi had cleft lip and palate (CLP) as compared with cleft lip (CL) nor in those where index cases had a bilateral lesion as compared to a unilateral one, nor when the index cases with CL(P) were female rather than males, nor when the index case was a female with bilateral lesion as compared to males with a unilateral one. Similarly fetal mortality was not increased in sibships in which the propositus had CP compared to those in which the index case was a female. These findings are contrary to some reports that claim to support a two-threshold model according to which individuals reaching the first one would be born with an oral cleft, and those reaching the second would be aborted. Our results, together with others, suggest the possibility that liability to oral clefts is independent of liability to fetal wastage.

Multiresistant extended-spectrum beta-lactamase-producing Klebsiella pneumoniae causing an outbreak of nosocomial bloodstream infection.

This article describes an outbreak of bloodstream infection due to clonal dissemination of multiresistant Klebsiella pneumoniae in a neonatal area, during August 1999, in Mexico City General Hospital. The intestinal tract was the likely reservoir, and intensification of Contact Precaution measures contained the outbreak.

Reconstruction of the nose damaged by cocaine.

Nasal snorting of cocaine crystals causes destruction of the septal and nasal mucosa, which eventually provides exposure of the septal cartilage and nasal bones. This exposure eventually leads to septal chrondritis and nasal bone osteomyelitis. As this process continues, the severe loss of cartilage and bone allows gradual to total collapse of the nose. Correction of this deformity is best achieved by supplying new lining; this is possible by turning nasolabial flaps into the nasal vestibule to replace the lost and released lining. Once this has been accomplished, costal cartilage grafts can be inserted along the bridge and alae to maintain the structural integrity of the reconstruction.

Dentin bond strength of packable composites using one-bottle adhesives.

PURPOSE: To evaluate the shear bond strength to dentin of packable composites using their respective one-bottle adhesives. MATERIALS AND METHODS: Human, noncarious extracted permanent molars stored in distilled water were used. Flat buccal and lingual dentin surfaces were ground wet on 600-grit silicon carbide paper. The teeth were then distributed at random into four groups of 8 teeth (16 surfaces) each: Group 1: Gluma Comfort Bond/Solitaire II; Group 2: Bond 1/Alert; Group 3: Prime & Bond NT/Surefil; Group 4: OptiBond Solo/Prodigy Condensable. Group 5: Single Bond/Z250 (control) Cylindrical samples of the materials were prepared in plastic molds and bonded to the dentin surface according to the manufacturers' instructions. All samples were placed in distilled water for 24 hrs, thermocycled for 500 cycles in distilled water at 6 degrees C and 60 degrees C and sheared with a universal testing machine at a crosshead speed of 0.5 mm/min. RESULTS: In MPa: Group 1: 24.39 +/- 3.54; Group 2: 28.96 +/- 4.62; Group 3: 30.77 +/- 4.71; Group 4: 30.82 +/- 3.29; Group 5: 24.93 +/- 5.14. ANOVA revealed that Groups 1 and 2 were statistically significantly different from the other groups; there was no statistically significant difference between Groups 2, 3 and 4.

Neutron angular distribution in a plasma focus obtained using nuclear track detectors.

The dense plasma focus (DPF) is a coaxial plasma gun in which a high-density, high-temperature plasma is obtained in a focused column for a few nanoseconds. When the filling gas is deuterium, neutrons can be obtained from fusion reactions. These are partially due to a beam of deuterons which are accelerated against the background hot plasma by large electric fields originating from plasma instabilities. Due to a beam-target effect, the angular distribution of the neutron emission is anisotropic, peaked in the forward direction along the axis of the gun. The purpose of this work is to illustrate the use of CR-39 nuclear track detectors as a diagnostic tool in the determination of the time-integrated neutron angular distribution. For the case studied in this work, neutron emission is found to have a 70% contribution from isotropic radiation and a 30% contribution from anisotropic radiation.