Exploring candidate biomarkers for rheumatoid arthritis through cardiovascular and cardiometabolic serum proteome profiling.

Introduction: RA patients are at higher risk of cardiovascular disease, influenced by therapies. Studying their cardiovascular and cardiometabolic proteome can unveil biomarkers and insights into related biological pathways. Methods: This study included two cohorts of RA patients: newly diagnosed individuals (n=25) and those with established RA (disease duration >25 years, n=25). Both cohorts were age and sex-matched with a control group (n=25). Additionally, a longitudinal investigation was conducted on a cohort of 25 RA patients treated with methotrexate and another cohort of 25 RA patients treated with tofacitinib for 6 months. Clinical and analytical variables were recorded, and serum profiling of 184 proteins was performed using the Olink technology platform. Results: RA patients exhibited elevated levels of 75 proteins that might be associated with cardiovascular disease. In addition, 24 proteins were increased in RA patients with established disease. Twenty proteins were commonly altered in both cohorts of RA patients. Among these, elevated levels of CTSL1, SORT1, SAA4, TNFRSF10A, ST6GAL1 and CCL18 discriminated RA patients and HDs with high specificity and sensitivity. Methotrexate treatment significantly reduced the levels of 13 proteins, while tofacitinib therapy modulated the expression of 10 proteins. These reductions were associated with a decrease in DAS28. Baseline levels of SAA4 and high levels of BNP were associated to the non-response to methotrexate. Changes in IL6 levels were specifically linked to the response to methotrexate. Regarding tofacitinib, differences in baseline levels of LOX1 and CNDP1 were noted between non-responder and responder RA patients. In addition, response to tofacitinib correlated with changes in SAA4 and TIMD4 levels. Conclusion: In summary, this study pinpoints molecular changes linked to cardiovascular disease in RA and proposes candidate protein biomarkers for distinguishing RA patients from healthy individuals. It also highlights how methotrexate and tofacitinib impact these proteins, with distinct alterations corresponding to each drug's response, identifying potential candidates, as SAA4, for the response to these therapies.

Pesticides luminescent sensing by a Tb3+-doped Zn metal-organic framework with selectivity towards parathion.

Organophosphorus pesticides (OPPs) such as parathion have extensive uses in agriculture and household applications. Chronic exposure to these pesticides can cause severe health and environmental issues. Therefore, a current ecological concern is associated with accumulating these noxious OPPs in food and water sources. In this work, a new Tb3+-doped Zn-LMOF (Zn-LMOF= (3D) {[Zn3(1,4 benzenedicarboxylate)3(EtOH)2]·(EtOH)0.6}∞) was synthesized by a solvent-free reaction between the Zn-LMOF and the salt TbCl3·6H2O using a high-speed ball milling. The Tb@Zn-LMOF was thoroughly characterized by multiple spectroscopic tools, including Scanning Electron Microscopy with Energy-Dispersive X-ray Spectroscopy, and studied in-depth as a luminescent sensor for a series of pesticides (parathion, malathion, methalaxil, carbofuran, iprodione, captan and glyphosate) in aqueous methanol. The Tb@Zn-LMOF is a long-lived green-emitting compound with luminescence originated by an efficient antenna effect from the excited energy levels of Zn-LMOF toward the 5D state of Tb3+ ions, as it is displayed by its strong emission bands at 488, 545, 585, and 620 nm and a lifetime of 1.01 ms upon excitation at 290 nm. Additions of pesticides to a neutral methanolic dispersion of Tb@Zn-LMOF modified its green emission intensity with a pronounced selectivity toward parathion within the micromolar concentration range. The detection limit for parathion was calculated to be 3.04 ± 0.2 µM for Tb@Zn-LMOF. Based on 31P NMR and mass spectrometry studies, it is attributed to the release of lanthanide ions from Tb@Zn-LMOF with the simultaneous formation of a Tb3+-parathion complex.

Water-soluble fluorescent chemosensor for sorbitol based on a dicationic diboronic receptor. Crystal structure and spectroscopic studies.

Selective recognition of saccharides by phenylboronic dyes capable of functioning in aqueous conditions is a central topic of modern supramolecular chemistry that impacts analytical sciences and biological chemistry. Herein, a new dicationic diboronic acid structure 11 was synthesized, structurally described by single-crystal X-ray diffraction, and studied in-depth as fluorescent receptor for six saccharides in pure water at pH = 7.4. This dicationic receptor 11 has been designed particularly to respond to sorbitol and involves two convergent and strongly acidified phenyl boronic acids, with a pKa of 6.6, that operate as binding sites. The addition of sorbitol in the micromolar concentration range to receptor 11 induces strong fluorescence change, but in the presence of fructose, mannitol, glucose, lactose and sucrose, only moderate optical changes are observed. This change in emission is attributed to a static complexation photoinduced electron transfer mechanism as evidenced by lifetime experiments and different spectroscopic tools. The diboronic receptor has a high affinity/selectivity to sorbitol (K = 31 800 M-1) over other saccharides including common interfering species such as mannitol and fructose. The results based on 1H, 11B NMR spectroscopy, high-resolution mass spectrometry and density functional theory calculations, support that sorbitol is efficiently bound to 11 in a 1 : 1 mode involving a chelating diboronate-sorbitol complexation. Since the experimental B⋯B distance (5.3 Å) in 11 is very close to the calculated distance from the DFT-optimized complex with sorbitol, the efficient binding is attributed to strong acidification and preorganization of boronic acids. These results highlight the usefulness of a new diboronic acid receptor with a strong ability for fluorescent recognition of sorbitol in physiological conditions.

Selective Luminescent Chemosensing of Chloride Based on a Cyclometalated Platinum(II) Complex in Water: Crystal Structures, Spectroscopic Studies, Extraction, and Bioimaging.

Selective anion sensing by luminescent chemosensors capable of operating in aqueous conditions is a central field of modern supramolecular chemistry that impacts analytical and biological chemistry. A cationic cyclometalated [Pt(N^C^N)NCCH3]OTf complex, 1 [N^C^N = 1,3-bis(1-(p-tolyl)-benzimidazol-2'-yl)benzene, OTf = triflate], was prepared, structurally described by single-crystal X-ray diffraction and studied in-depth as a luminescent chemosensor for anions in aqueous phase and solid state. A series of related neutral [Pt(N^C^N)X] complexes (X = Cl, 2; CN, 3 and I, 4) were formed readily upon treatment of 1 with the respective NaX salt in aqueous media and were described structurally by X-ray diffraction. Complex 1 is hydrostable with phosphorescent green emission originated by intraligand transitions, and [dyz(Pt) → π*(N^C^N)] charge transfer transitions, as evidenced by TD-DFT calculations and lifetime. Additions of halides, pseudohalides, oxyanions, and dicarboxylates to a neutral aqueous solution of 1 modified its green emission intensity with a pronounced affinity (K = 1.5 × 105 M-1) and turn-on signal toward Cl- within the micromolar concentration range. Pt complex 1 is two orders of magnitude more selective for Cl- than the other halides, CN- and basic oxyanions. Such Cl- affinity for a metal-based chemosensor in aqueous media is still rare. On the basis of X-ray crystallographic analysis and multiple spectroscopic tools (NMR, UV-vis, luminescence, MS, lifetimes) the origin of this selectivity hinges on the cooperative three-point recognition involving one coordination bond (Pt-Cl) and two convergent short C-H···Cl- contacts. This strong affinity and efficient optical response can be utilized in quantitative Cl- sensing in real samples and solid-liquid extractions. Additionally, chloro-Pt complex, 2 may be relevant to bioimaging as a marker for cell nuclei, as revealed by its emission within living cells and intracellular distribution by confocal microscopic studies. These results demonstrate the usefulness of the new water-stable luminescent Pt-N^C^N complexes as effective analytical tools in anion sensing and extraction agents.

Fluorescence Sensing of Monosaccharides by Bis-boronic Acids Derived from Quinolinium Dicarboxamides: Structural and Spectroscopic Studies.

Three new diboronic acid-substituted bisquinolinium salts were synthesized, structurally described by single-crystal X-ray diffraction, and studied in-depth as fluorescent receptors for six monosaccharides and two open-chain polyols in water at physiological pH. The dicationic pyridine-2,6-dicarboxamide-based receptors contain two N-quinolinium rings as the fluorescent units covalently linked to three different isomers of phenylboronic acid (ortho, 2; meta, 3; and para, 4) as chelating binding sites for polyols. Additions of glucose/fructose in the micromolar concentration range to receptors 2 and 3 induce significant fluorescence changes, but in the presence of arabinose, galactose, mannose, and xylose, only modest optical changes are observed. This optical change is attributed to a static photoinduced electron transfer mechanism. The meta-diboronic receptor 3 exhibited a high affinity/selectivity toward glucose (K = 3800 M-1) over other monosaccharides including common interfering species such as fructose and mannitol. Based on multiple spectroscopic tools, electrospray ionization high-resolution mass spectrometry, crystal structures, and density functional theory calculations, the binding mode between 3 and glucose is proposed as a 1:1 complex with the glucofuranose form involving a cooperative chelating diboronate binding. These results demonstrate the usefulness of a new set of cationic fluorescent diboronic acid receptors with a strong ability for optical recognition of glucose in the sub-millimolar concentration range.

Dietary Mg Supplementation Decreases Oxidative Stress, Inflammation, and Vascular Dysfunction in an Experimental Model of Metabolic Syndrome with Renal Failure.

BACKGROUND: Metabolic syndrome (MetS) and chronic kidney disease (CKD) are commonly associated with cardiovascular disease (CVD) and in these patients Mg concentration is usually decreased. This study evaluated whether a dietary Mg supplementation might attenuate vascular dysfunction through the modulation of oxidative stress and inflammation in concurrent MetS and CKD. METHODS: A rat model of MetS (Zucker strain) with CKD (5/6 nephrectomy, Nx) was used. Nephrectomized animals were fed a normal 0.1%Mg (MetS+Nx+Mg0.1%) or a supplemented 0.6%Mg (MetS+Nx+Mg0.6%) diet; Sham-operated rats with MetS receiving 0.1%Mg were used as controls. RESULTS: As compared to controls, the MetS+Nx-Mg0.1% group showed a significant increase in oxidative stress and inflammation biomarkers (lipid peroxidation and aortic interleukin-1b and -6 expression) and Endothelin-1 levels, a decrease in nitric oxide and a worsening in uremia and MetS associated pathology as hypertension, and abnormal glucose and lipid profile. Moreover, proteomic evaluation revealed changes mainly related to lipid metabolism and CVD markers. By contrast, in the MetS+Nx+Mg0.6% group, these parameters remained largely similar to controls. CONCLUSION: In concurrent MetS and CKD, dietary Mg supplementation reduced inflammation and oxidative stress and improved vascular function.

The direct effect of fibroblast growth factor 23 on vascular smooth muscle cell phenotype and function.

BACKGROUND: In chronic kidney disease (CKD) patients, increased levels of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality. The relationship between FGF23 and heart hypertrophy has been documented, however, it is not known whether FGF23 has an effect on vasculature. Vascular smooth muscle cells VSMCs may exhibit different phenotypes; our hypothesis is that FGF23 favours a switch from a contractile to synthetic phenotype that may cause vascular dysfunction. Our objective was to determine whether FGF23 may directly control a change in VSMC phenotype. METHODS: This study includes in vitro, in vivo and ex vivo experiments and evaluation of patients with CKD stages 2-3 studying a relationship between FGF23 and vascular dysfunction. RESULTS: In vitro studies show that high levels of FGF23, by acting on its specific receptor FGFR1 and Erk1/2, causes a change in the phenotype of VSMCs from contractile to synthetic. This change is mediated by a downregulation of miR-221/222, which augments the expression of MAP3K2 and PAK1. miR-221/222 transfections recovered the contractile phenotype of VSMCs. Infusion of recombinant FGF23 to rats increased vascular wall thickness, with VSMCs showing a synthetic phenotype with a reduction of miR-221 expression. Ex-vivo studies on aortic rings demonstrate also that high FGF23 increases arterial stiffening. In CKD 2-3 patients, elevation of FGF23 was associated with increased pulse wave velocity and reduced plasma levels of miR-221/222. CONCLUSION: In VSMCs, high levels of FGF23, through the downregulation of miR-221/222, causes a change to a synthetic phenotype. This change in VSMCs increases arterial stiffening and impairs vascular function, which might ultimately worsen cardiovascular disease.

Determination of the Anthropometric Measures of the Lips by Age Groups in the Mestiza Population.

Measurements from a certain population may show a similar pattern that allows an alteration to be easily recognized and enable a better surgical approach. In our population, the changes in the anthropometric measurements of the lips are unknown, so our objective is to determine the variations in these measurements by decades of age to achieve a better aesthetic and reconstructive surgical approach. Anthropometric measurements of the lips were taken with a vernier in relation to the previously marked anatomical points. The sample consists of 174 patients who came for care not related to labial pathologies with ages between 20 and 80 years with Mexican nationality. We use the sample calculation formula to estimate an average, with an alpha error of 0.5 and a tolerance of 2 mm of the data for the measurements of the height of the lower face with an average measurement of 56.2 mm and a SD of 8.87 mm of the Marzena's article. Wyganowska-Swiatkowska and colleagues Average measurements were obtained, where a progressive longitudinal increase in measures: al-ch, sbl-cph, sn-Is, li-sto, cph-Is, li-sl, ch-li, li-pg according to aging is confirmed. In contrast, the ch-cph and ch-sbl measures, remain the same despite the aging, showing greater changes in the sagittal plane than in the parasagittal. The study only shows measures of length, so caring out a magnetic resonance imaging study to also measure the volume and perform it with a larger sample to have the optimal standard is further needed.

Individual Cofactors and Multisensory Contributions to the Postural Sway of Adults with Diabetes.

To assess the interactions between individual cofactors and multisensory inputs on the postural sway of adults with type 2 diabetes and healthy subjects, 69 adults accepted to participate in the study (48 with/ 21 without diabetes). Assessments included neuro-otology (sinusoidal-rotation and unilateral-centrifugation), ophthalmology and physiatry evaluations, body mass index (BMI), physical activity, quadriceps strength, the ankle/brachial index and polypharmacy. Postural sway was recorded on hard/soft surface, either with eyes open/closed, or without/with 30° neck extension. The proportional differences from the baseline of each condition were analyzed using Multivariate and Multivariable analyses. Patients with polyneuropathy and no retinopathy showed visual dependence, while those with polyneuropathy and retinopathy showed adaptation. Across sensory challenges, the vestibulo-ocular gain at 1.28 Hz and the BMI were mainly related to changes in sway area, while the dynamic visual vertical was mainly related to changes in sway length. The ankle/brachial index was related to the effect of neck extension, with contributions from quadriceps strength/physical activity, polyneuropathy and polypharmacy. Across conditions, men showed less sway than women did. In conclusion, in adults with diabetes, sensory inputs and individual cofactors differently contribute to postural stability according to context. Rehabilitation programs for adults with diabetes may require an individualized approach.

Information and consensus document for the detection and management of chronic kidney disease.

Chronic kidney disease (CKD) is a major public health problem worldwide that affects more than 10% of the Spanish population. CKD is associated with high comorbidity rates, poor prognosis and major consumption of health system resources. Since the publication of the last consensus document on CKD seven years ago, little evidence has emerged and few clinical trials on new diagnostic and treatment strategies in CKD have been conducted, apart from new trials in diabetic kidney disease. Therefore, CKD international guidelines have not been recently updated. The rigidity and conservative attitude of the guidelines should not prevent the publication of updates in knowledge about certain matters that may be key in detecting CKD and managing patients with this disease. This document, also prepared by 10 scientific associations, provides an update on concepts, clarifications, diagnostic criteria, remission strategies and new treatment options. The evidence and the main studies published on these aspects of CKD have been reviewed. This should be considered more as an information document on CKD. It includes an update on CKD detection, risk factors and screening; a definition of renal progression; an update of remission criteria with new suggestions in the older population; CKD monitoring and prevention strategies; management of associated comorbidities, particularly in diabetes mellitus; roles of the Primary Care physician in CKD management; and what not to do in Nephrology. The aim of the document is to serve as an aid in the multidisciplinary management of the patient with CKD based on current recommendations and knowledge.

La bioética como un pilar de la formación de profesores de biología

Propósito/Contexto. En este artículo se presenta una propuesta acerca de cómo incorporar (o robustecer) la educación bioética en la formación inicial de profesores de biología en el contexto colombiano. Metodología/Enfoque. Se inicia mostrando, a grandes rasgos, cuál es la situación de la enseñanza de la bioética en Colombia, en aras de situar el contexto en el que se inscribe la propuesta. Posteriormente, se define qué es la bioética, con base en los propósitos del artículo, para lo cual se acude al concepto de bioética global de Potter y se amplía, incorporando otras dimensiones, más allá de la bioética médica y la ambiental. Resultados/Hallazgos. La bioética global se complementa con algunos enfoques: esta perspectiva ha de ser práctica, laica, inter y transdisciplinar, y estar en estrecha relación con la educación. Se mencionan algunas situaciones de orden nacional, en Colombia, que implican debates bioéticos y que podrían desempeñar un rol preponderante en la formación de profesores de biología, situaciones que se sugiere abordar con base en unas estrategias de enseñanza particulares. Discusión/Conclusiones/Contribuciones. Se afianza la idea de por qué es necesario que los profesores tengan una educación bioética; se enumeran las limitaciones de la propuesta planteada y se enfatizan las perspectivas y los retos que de ella devienen.

Purpose/Context. This article presents a proposal on how to incorporate (or strengthen) bioethics education into the initial training of biology teachers in the Colombian context. Materials and methods/Approach. It begins with an overview of bioethics teaching in Colombia to define the context of the proposal. Subsequently, bioethics is defined based on the purposes of the article, for which Potter's concept of global bioethics is used and expanded, incorporating other dimensions beyond medical bioethics and environmental bioethics. Results/Findings. Some approaches complement global bioethics: This perspective must be practical, secular, inter- and transdisciplinary, and closely related to education. We mention some national situations that involve bioethical debates, which could play a preponderant role in the training of biology teachers. These situations should be addressed using particular teaching strategies. Discussion/Conclusions/Contributions. We reinforce the idea of why teachers must have a bioethical education, list the limitations of our proposal, and emphasize the perspectives and challenges arising from it.

Objetivo/contexto. Neste artigo se apresenta uma proposta sobre como incorporar (ou robustecer) a educação bioética na formação inicial de professores de biologia, no contexto colombiano. Metodologia/Abordagem. Começa-se mostrando, em traços gerais, qual é a situação do ensino da bioética na Colômbia, em vista de situar o contexto no qual se inscreve a proposta. Posteriormente se define o que é a bioética, com base nos propósitos do artigo, para o qual se recorre ao conceito de bioética global de Potter e se amplia, incorporando outras dimensões, além da bioética médica e da bioética ambiental. Resultados/Descobertas. A bioética global se complementa com alguns enfoques: esta perspectiva há de ser prática, laica, inter e transdisciplinar, e estar em estreita relação com a educação. Mencionam-se algumas situações de ordem nacional, na Colômbia, que implicam debates bioéticos e que poderiam desempenhar um papel preponderante na formação de professores de biologia, situações que se sugere abordar com base em estratégias de ensino particulares. Discussão/Conclusões/Contribuições. Reforça-se a ideia de porque é necessário que os professores tenham uma educação bioética; enumeram-se as limitações da proposta apresentada e enfatizam-se as perspectivas e os desafios que dela derivam.

14-Electron Rh and Ir silylphosphine complexes and their catalytic activity in alkene functionalization with hydrosilanes.

Herein we report an experimental and computational study of a family of four coordinated 14-electron complexes of Rh(iii) devoid of agostic interactions. The complexes [X-Rh(κ3(P,Si,Si)PhP(o-C6H4CH2SiiPr2)2], where X = Cl (Rh-1), Br (Rh-2), I (Rh-3), OTf (Rh-4), Cl·GaCl3 (Rh-5); derive from a bis(silyl)-o-tolylphosphine with isopropyl substituents on the Si atoms. All five complexes display a sawhorse geometry around Rh and exhibit similar spectroscopic and structural properties. The catalytic activity of these complexes and [Cl-Ir(κ3(P,Si,Si)PhP(o-C6H4CH2SiiPr2)2], Ir-1, in styrene and aliphatic alkene functionalizations with hydrosilanes is disclosed. We show that Rh-1 catalyzes effectively the dehydrogenative silylation of styrene with Et3SiH in toluene while it leads to hydrosilylation products in acetonitrile. Rh-1 is an excellent catalyst in the sequential isomerization/hydrosilylation of terminal and remote aliphatic alkenes with Et3SiH including hexene isomers, leading efficiently and selectively to the terminal anti-Markonikov hydrosilylation product in all cases. With aliphatic alkenes, no hydrogenation products are observed. Conversely, catalysis of the same hexene isomers by Ir-1 renders allyl silanes, the tandem isomerization/dehydrogenative silylation products. A mechanistic proposal is made to explain the catalysis with these M(iii) complexes.

TWEAK Signaling Pathway Blockade Slows Cyst Growth and Disease Progression in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD), cyst development and enlargement lead to ESKD. Macrophage recruitment and interstitial inflammation promote cyst growth. TWEAK is a TNF superfamily (TNFSF) cytokine that regulates inflammatory responses, cell proliferation, and cell death, and its receptor Fn14 (TNFRSF12a) is expressed in macrophage and nephron epithelia. METHODS: To evaluate the role of the TWEAK signaling pathway in cystic disease, we evaluated Fn14 expression in human and in an orthologous murine model of ADPKD. We also explored the cystic response to TWEAK signaling pathway activation and inhibition by peritoneal injection. RESULTS: Meta-analysis of published animal-model data of cystic disease reveals mRNA upregulation of several components of the TWEAK signaling pathway. We also observed that TWEAK and Fn14 were overexpressed in mouse ADPKD kidney cysts, and TWEAK was significantly high in urine and cystic fluid from patients with ADPKD. TWEAK administration induced cystogenesis and increased cystic growth, worsening the phenotype in a murine ADPKD model. Anti-TWEAK antibodies significantly slowed the progression of ADPKD, preserved renal function, and improved survival. Furthermore, the anti-TWEAK cystogenesis reduction is related to decreased cell proliferation-related MAPK signaling, decreased NF-κB pathway activation, a slight reduction of fibrosis and apoptosis, and an indirect decrease in macrophage recruitment. CONCLUSIONS: This study identifies the TWEAK signaling pathway as a new disease mechanism involved in cystogenesis and cystic growth and may lead to a new therapeutic approach in ADPKD.

Pseudoatetosis de los miembros superiores como manifestación del déficit de vitamina B12: a propósito de un caso / Pseudoathetosis of the upper limbs as a manifestation of vitamin B12 deficit: about a case

RESUMEN INTRODUCCIÓN: La ganglionopatía sensitiva es una rara complicación del déficit de vitamina B12, la cual da origen a un espectro de síntomas neurológicos que incluyen alteración de la sensibilidad vibratoria, propiocepción, ataxia y, con menor frecuencia, trastornos del movimiento. La pseudoatetosis es una presentación muy inusual. CASO CLÍNICO: Un paciente masculino de 73 años se presenta con parestesias y torpeza de las cuatro extremidades, dolor tipo urente en plantas de pies y manos, inestabilidad postural y limitación para la marcha. En la exploración neurológica se encuentra hipoestesia y ataxia sensitiva de las cuatro extremidades, con presencia de pseudoatetosis de los miembros superiores como consecuencia de ganglionopatía por déficit de vitamina B12 demostrada por la imagen típica de "V" invertida, debido a compromiso de las proyecciones centrales las neuronas sensitivas mielinizadas en RMN de columna cervicotoráccica. A los cuatro meses se reporta mejoría del déficit propioceptivo y corrección del trastorno de movimiento gracias a la reposición de la cianocobalamina intramuscular. Hasta el momento no se presenta patología neoplásica, autoinmune o infecciosa. CONCLUSIONES: La ganglionopatía sensitiva por déficit de vitamina B12 es una condición potencialmente reversible y subdiagnosticada que puede manifestarse ocasionalmente con trastornos del movimiento. Debe sospecharse en pacientes con déficits sensitivos por compromiso de fibra gruesa. Su pronóstico es favorable si la causa del déficit se documenta tempranamente y se hace reposición de dicha vitamina.

SUMMARY INTRODUCTION: Sensory ganglionopathy is a rare complication of vitamin B12 deficiency, causing an spectrum of neurologic symptoms such as abnormal vibratory sensitivity, proprioception, gait disturbance and rarely movement disorders like pseudoatetosis and dystonia. CLINICAL CASE: A73-year-old man was admitted with numbness and clumsiness of his extremities, burning pain on palms and soles, postural instability and impaired walking. Neurological examination demonstrated hypesthesia and sensory ataxia of four limbs with associated pseudo athetoid movements of the upper limbs as a consequence of ganglionopathy by vitamin B12 deficiency, showing typical MRI inverted "V" sign due to degeneration of central projections from large sensory neurons, which was successfully treated with IM cyanocobalamin 4 months later. CONCLUSIONS: Sensory ganglionopathy in B12 deficit is a potentially reversible and underdiagnosed condition, which occasionally can present with movement disorders. Must be suspected in patiens presenting with sensory deficits depending on richly myelinated axons. Usually with good prognosis after identifying the deficit's cause and giving propper treatment.

Economía política de la política agraria en Colombia: de la Ley 200 de 1936 al Acuerdo de Paz de 2016 / Political economy of agricultural policy in Colombia: from Law 200 of 1936 to the 2016 Peace Agreement / Economia política da política agrícola na Colômbia: da Lei 200 de 1936 ao Acordo de Paz de 2016

RESUMEN En esta investigación se estudia la política agraria en Colombia y su relación con el conflicto entre campesinos y terratenientes, entorno a los activos productivos rurales. Se aborda la discusión sobre el acceso a la tierra y se examina cada uno de los planes nacionales de desarrollo, para elaborar una trazabilidad histórica de la política agraria en Colombia durante el periodo 1936-2016. El problema de investigación se deriva de la persistencia de la pobreza y marginación social de la población rural, identificada en la Misión Rural y reconocida en el Acuerdo de Paz de 2016. Se concluye que la configuración histórica del Estado fue incorporando los intereses de las estructuras de poder económico y político de cada momento. Cuando el Estado quiso resolver el conflicto por la tierra, la capacidad ejecutiva de las instituciones era limitada y tergiversada por los grupos de interés dominantes que tenían la ventaja de redactar las leyes y aplicarlas de acuerdo con sus preferencias. Por esta razón las condiciones socioeconómicas de los campesinos siguen siendo parecidas a las que tenían hace un siglo. CLASIFICACIÓN JEL P16, P26, O12, O13, O43

ABSTRACT This research studies agrarian policy in Colombia and its relationship with the conflict between peasants and landowners, around rural productive assets. The discussion on access to land is approached and each one of the national development plans is examined, to elaborate a historical traceability of the agrarian policy in Colombia during the period 1936-2016. The research problem stems from the persistence of poverty and social marginalization of the rural population, identified in the rural mission and recognized in the 2016 peace agreement. It is concluded that the historical configuration of the State was incorporating the interests of the economic and political power structures of each moment. When the State wanted to resolve the conflict over land, the executive capacity of the institutions was limited and distorted by the dominant interest groups who had the advantage of writing the laws and applying them according to their preferences. For this reason, the socioeconomic conditions of the peasants continue to be similar to those they had a century ago. JEL CLASSIFICATION P16, P26, O12, O13, O43

RESUMO Esta pesquisa estuda a política agrária na Colômbia e sua relação com o conflito entre camponeses e proprietários de terras em torno dos ativos produtivos rurais. Aborda-se a discussão sobre o acesso à terra e examina-se cada um dos planos nacionais de desenvolvimento, para elaborar uma rastreabilidade histórica da política agrária na Colômbia durante o período 1936-2016. O problema de pesquisa decorre da persistência da pobreza e marginalização social da população rural, identificada na Missão Rural e reconhecida no Acordo de Paz 2016. Conclui-se que a configuração histórica do Estado foi incorporando os interesses das estruturas do poder econômico e político de cada momento. Quando o Estado queria resolver o conflito de terras, a capacidade executiva das instituições era limitada e distorcida pelos grupos de interesse dominantes que tinham a vantagem de redigir as leis e aplicá-las de acordo com suas preferências. Por isso, as condições socioeconômicas dos camponeses continuam semelhantes às de um século atrás. CLASSIFICAÇÃO JEL P16, P26, O12, O13, O43

Obesidad abdominal y perfil lipídico en pacientes con hiperplasia suprarrenal congénita por déficit de 21 hidroxilasa / Abdominal Obesity and Lipid Profile in Patients with 21-Hydroxylase-Deficient Congenital Suprarenal Hyperplasia

RESUMEN Introducción: Existen discrepancias en relación con el aumento de la adiposidad abdominal de los pacientes con hiperplasia suprarrenal congénita (HSC) y la influencia sobre ella de factores clínicos, hormonales y relacionados con la dosis y el tiempo de uso del tratamiento esteroideo. Objetivo: Describir la relación entre la obesidad abdominal, la dosis, el tiempo de tratamiento esteroideo los niveles de andrógenos circulantes y el perfil lipídico en los pacientes tratados por este padecimiento. Métodos: Estudio descriptivo, transversal, que incluyó a todos los niños y adolescentes con hiperplasia suprarrenal congénita por déficit de 21 hidroxilasa que recibían tratamiento esteroideo sustitutivo, atendidos en el departamento de endocrinología pediátrica del Instituto Nacional de Endocrinología durante el periodo 2000-2015. Se estudiaron variables clínicas, bioquímicas y hormonales. Para las variables cualitativas se calcularon frecuencias absolutas y porcentajes, media y desviación estándar para las variables cuantitativas. Se evaluaron asociaciones utilizando el coeficiente de correlación de Spearman y la prueba chi cuadrado para evaluar la significación estadística de la posible asociación, considerada cuando p < 0,05. Resultados: Fueron estudiados 29 pacientes, 24 (82,8 por ciento) con sexo social femenino, una edad promedio de 10,9 ± 6,27 años, edad al diagnóstico de 1,9 años ± 2,7 años y edad de inicio del tratamiento 2,03 ± 2,7 años. Las formas clásicas predominaron con 23 pacientes (79,3 por ciento), 11 perdedoras de sal (47,8 por ciento) y 12 formas virilizantes simples, solo 6 correspondieron a las formas no clásicas (20,7 por ciento). En los tres grupos se comprobó adiposidad abdominal incrementada según el índice abdomen/talla (0,52 vs. 0,51 vs. 0,51). La utilización de mayores dosis de esteroides se correlacionó de manera positiva con mayor circunferencia de cintura (p < 0,05) y abdomen (p < 0.01). En 13 (44,8 por ciento) pacientes se comprobó obesidad abdominal y el perfil lipídico mostró valores normales en todos los casos estudiados. Conclusiones: La obesidad abdominal constituye un signo frecuente en los pacientes con HSC. Es preciso monitorear con precisión las dosis de esteroides empleadas, establecer estrategias de seguimiento más completas y estimular estilos de vida saludables, lo que redundará a largo plazo en menores consecuencias cardiometabólicas(AU)

ABSTRACT Introduction: Some disagreement exists concerning the increase in abdominal adiposity in patients with congenital adrenal hyperplasia and the influence of clinical, hormonal and dose-related factors and the time of steroid treatment use. Objective: To identify the presence of abdominal obesity and its relationship with the dose and time of steroid treatment, as well as with the levels of circulating androgens, and describe the lipid profile of these patients. Methods: Cross-sectional and descriptive study that included all the children and adolescents with 21-hydroxylase-deficient congenital adrenal hyperplasia and who received steroid replacement treatment, treated at the pediatric endocrinology department of the National Institute of Endocrinology, in the period 2000-2015. Clinical, biochemical and hormonal variables were studied. For the qualitative variables, absolute frequencies and percentages; mean and standard deviations were calculated for the quantitative variables. Associations were evaluated using the Spearman correlation coefficient. The chi-square test was used to evaluate the statistical significance of the possible association, considered when p < 0.05. Results: Twenty-nine patients were studied: 24 (82.8 percent) with female social sex, an average age of 10.9 ± 6.27 years, age of diagnosis at 1.9 ± 2.7 years, and age of treatment beginning at 2.03 ± 2.7 years. The classical forms predominated in 23 patients (79.3 percent): 11 salt losers (47.8 percent) and 12 simple virializing forms; only six corresponded to non-classical forms (20.7 percent). In the three groups, increased abdominal adiposity was found, according to abdomen/height index (0.52 vs. 0.51 vs. 0.51). The use of higher doses of steroids was correlated positively with greater circumference of waist (p < 0.05) and abdomen (p < 0.01). In 13 (44.8 percent) patients, abdominal obesity was found, while the lipid profile showed normal values in all the cases studied. Conclusions: Abdominal obesity is a frequent sign in patients with congenital adrenal hyperplasia. It is necessary to monitor accurately the doses of steroids used, establish more comprehensive follow-up strategies, and encourage healthy lifestyles, which will result in fewer long-term cardiometabolic consequences(AU)