Urinary metabolomic profiling of a cohort of Colombian patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune and multisystem disease with a high public health impact. Lupus nephritis (LN), commonly known as renal involvement in SLE, is associated with a poorer prognosis and increased rates of morbidity and mortality in patients with SLE. Identifying new urinary biomarkers that can be used for LN prognosis or diagnosis is essential and is part of current active research. In this study, we applied an untargeted metabolomics approach involving liquid and gas chromatography coupled with mass spectrometry to urine samples collected from 17 individuals with SLE and no kidney damage, 23 individuals with LN, and 10 clinically healthy controls (HCs) to identify differential metabolic profiles for SLE and LN. The data analysis revealed a differentially abundant metabolite expression profile for each study group, and those metabolites may act as potential differential biomarkers of SLE and LN. The differential metabolic pathways found between the LN and SLE patients with no kidney involvement included primary bile acid biosynthesis, branched-chain amino acid synthesis and degradation, pantothenate and coenzyme A biosynthesis, lysine degradation, and tryptophan metabolism. Receiver operating characteristic curve analysis revealed that monopalmitin, glycolic acid, and glutamic acid allowed for the differentiation of individuals with SLE and no kidney involvement and individuals with LN considering high confidence levels. While the results offer promise, it is important to recognize the significant influence of medications and other external factors on metabolomics studies. This impact has the potential to obscure differences in metabolic profiles, presenting a considerable challenge in the identification of disease biomarkers. Therefore, experimental validation should be conducted with a larger sample size to explore the diagnostic potential of the metabolites found as well as to examine how treatment and disease activity influence the identified chemical compounds. This will be crucial for refining the accuracy and effectiveness of using urine metabolomics for diagnosing and monitoring lupus and lupus nephritis.

A scalable approach for short-term disease forecasting in high spatial resolution areal data.

Short-term disease forecasting at specific discrete spatial resolutions has become a high-impact decision-support tool in health planning. However, when the number of areas is very large obtaining predictions can be computationally intensive or even unfeasible using standard spatiotemporal models. The purpose of this paper is to provide a method for short-term predictions in high-dimensional areal data based on a newly proposed "divide-and-conquer" approach. We assess the predictive performance of this method and other classical spatiotemporal models in a validation study that uses cancer mortality data for the 7907 municipalities of continental Spain. The new proposal outperforms traditional models in terms of mean absolute error, root mean square error, and interval score when forecasting cancer mortality 1, 2, and 3 years ahead. Models are implemented in a fully Bayesian framework using the well-known integrated nested Laplace estimation technique.

Big problems in spatio-temporal disease mapping: Methods and software.

BACKGROUND AND OBJECTIVE: Fitting spatio-temporal models for areal data is crucial in many fields such as cancer epidemiology. However, when data sets are very large, many issues arise. The main objective of this paper is to propose a general procedure to analyze high-dimensional spatio-temporal areal data, with special emphasis on mortality/incidence relative risk estimation. METHODS: We present a pragmatic and simple idea that permits hierarchical spatio-temporal models to be fitted when the number of small areas is very large. Model fitting is carried out using integrated nested Laplace approximations over a partition of the spatial domain. We also use parallel and distributed strategies to speed up computations in a setting where Bayesian model fitting is generally prohibitively time-consuming or even unfeasible. RESULTS: Using simulated and real data, we show that our method outperforms classical global models. We implement the methods and algorithms that we develop in the open-source R package bigDM where specific vignettes have been included to facilitate the use of the methodology for non-expert users. CONCLUSIONS: Our scalable methodology proposal provides reliable risk estimates when fitting Bayesian hierarchical spatio-temporal models for high-dimensional data.

A Rarity Among the Rare: Psychiatric Manifestations in a Young Woman With Stiff-Person Syndrome.

Stiff-person syndrome (SPS) is a rare progressive neurologic disease associated with autoantibodies against glutamic acid decarboxylase, an intracellular enzyme involved in the production of gamma-aminobutyric acid.  We present a case involving a 35-year-old Haitian female who was placed under the Baker Act in the emergency department for suicidal behavior and acute psychosis. She has a history of SPS with a positive glutamic acid decarboxylase (GAD) antibody, a condition most commonly found in females between 20 and 50 years of age. The condition was managed by an outpatient neurologist using diazepam, baclofen, and monthly intravenous immunoglobulin treatments. She also has an extensive history of organic neurological conditions, including traumatic brain injury at 18 years old and COVID-19-related anoxic encephalitis that occurred in December 2020. Both psychiatric and neurological physical exams were completed. They revealed a cerebellar tremor, bilateral ptosis, poor eye contact, decreased concentration, poor insight, depressed mood, flat affect, poor judgement, delusional thoughts and a disorganized thought process with tangential speech. CT and MRI imaging of the brain showed no acute intracranial abnormalities. A quantitative titer of the GAD antibody was completed and shown to be elevated >250IU/mL. Depakote 500mg twice daily and risperidone 3mg twice daily were prescribed. The patient had progressive improvement of psychosis including delusional thoughts over the following five days and was able to be discharged with instructions to follow-up with outpatient neurology.

Efectos de la competencia larvaria intraespecífica de Aedes aegypti y Aedes albopictus en condiciones de laboratorio / Effects of intraspecific larval competence of Aedes aegypti and Aedes albopictus under laboratory conditions

RESUMEN Introducción: Aedes aegypti y Aedes albopictus constituyen dos de las especies más importantes de mosquitos, debido a que son vectores primarios de enfermedades emergentes y reemergentes que representan una amenaza significativa para la salud pública. Objetivo: Evaluar el efecto de la competencia larvaria intraespecífica causada por baja y alta densidad de dos poblaciones de Ae. aegypti y Ae. albopictus sobre aspectos de su ciclo de vida en condiciones de laboratorio. Métodos: Se utilizaron dos poblaciones de mosquitos, Ae. aegypti y Ae. albopictus, ambas colectadas en estado de larva en el Reparto Juan de Dios Fraga, La Lisa, La Habana, Cuba. Se establecieron condiciones de baja (70 larvas) y alta densidad larvaria (140 larvas) en cada réplica para cada una de las especies. Se emplearon larvas desde el primer estadio, que se siguieron hasta la formación de los adultos. Se evaluaron las variables duración del ciclo larvario, supervivencia larvaria, así como talla y supervivencia de hembras adultas, respectivamente. Resultados: Se encontró que las variables evaluadas no se afectaron en condiciones de baja densidad larvaria. Sin embargo, el efecto de la relación larvaria intraespecífica bajo condiciones de alta densidad presentada en los hábitats de Ae. aegypti y Ae. albopictus tuvo un efecto negativo en cada una de las variables del ciclo de vida evaluadas. Conclusiones: Estas alteraciones observadas son importantes dentro de los componentes de la capacidad vectorial, con implicaciones en la epidemiología de las enfermedades transmitidas por estos mosquitos. Los resultados pudieran extrapolarse al comportamiento de estos mosquitos en su entorno natural. Estas condiciones podrían aumentar los patrones de transmisión del virus del dengue, así como un mayor riesgo de infección para la población humana.

ABSTRACT Introduction: Aedes aegypti and Aedes albopictus are two of the most important mosquito species, since they are the main vector of emerging and re-emerging diseases that represent a significant threat to public health. Objective: To evaluate the effect of intraspecific larval competence caused by low and high density in two populations of Ae. aegypti and Ae. albopictus on aspects of their life cycles under laboratory conditions. Methods: Two mosquitos populations were used, Ae. aegypti and Ae. albopictus, both collected during their larval stage in Juan de Dios Fraga town, La Lisa, Havana, Cuba. Low (70 larvae) and high (140 larvae) density conditions were established in each replication for each species. Larvae from the first stage were used and follow-up was established until adults emerged. Variables such as: larval cycle duration, larval survival, and adult female size and survival were evaluated. Results: The variables evaluated were not affected under low larval density conditions. However, the intraspecific larval relationship under high density conditions in Ae. aegypti and Ae. albopictus habitats had a negative effect in each of the variables of the life cycles. Conclusions: The observed alterations are important within the components of vectorial capacity, with implications for the epidemiology of these mosquitos-borne diseases. The results could be extended to the behavior of these mosquitoes in their natural environment. These conditions could increase the transmission patterns of dengue virus and the risk of infection for the human population.

Serum cortisol levels and neuropsychological impairments in patients diagnosed with Fibromyalgia.

OBJECTIVE: To describe the relationship between neuropsychological variables and serum cortisol levels as a measure of physiological stress in patients with fibromyalgia. METHODOLOGY: A sample of 60 women was intentionally selected: 30 with Fibromyalgia diagnosis and 30 with normal controls. Cortisol levels were determined using two blood samples (AM and PM) and a neuropsychological and emotional battery was applied with a standardized protocol in Colombian population to evaluate different cognitive domains. Comparative and correlational non-parametric analyzes were performed, a multiple regression analysis to determine influences between variables. RESULTS: Significant differences between the study groups in the neuropsychological variables (attention, memory, language, visual-constructive praxis and executive functions (EF), (p<0.05) were found, obtaining better scores in the control group. Significant correlations between the cortisol profile, with false acknowledgments of Rey auditory- verbal learning test, and with perseverative errors of the Wisconsin test were found. Multiple regression analysis predicts the influence of memory and EF variables on the cortisol profile in an 88.7%. CONCLUSIONS: The findings show that, in patients with FM, there are neuropsychological alterations, mainly in executive functioning (cognitive flexibility) and episodic memory (evocation and storage). Likewise, executive dysfunction is related to physiological stress reciprocally and in turn are conditioned by emotional alterations such as symptoms of depression, which supports the neurophysiological model that compromises the hypothalamic-pituitary-adrenal axis and the prefrontal cortex, rich in corticosteroid receptors.

Síntomas afectivo-conductuales y estrategias de afrontamiento del dolor en pacientes con fibromialgia (FM) / Affective - behavioral symptoms and coping strategies of pain in patients with fibromyalgia (FM)

Resumen Objetivo: La fibromialgia (FM) es un síndrome de dolor crónico generalizado, asociado a alteraciones emocionales y comportamentales. El objetivo de este estudio fue identificar los síntomas afectivo-conductuales y las estrategias cognitivas de afrontamiento en la percepción de dolor de pacientes con FM. Material y métodos: Se realizó un estudio de corte transversal, con análisis de casos y controles, con una muestra de dos grupos de mujeres, en la ciudad de Barranquilla (Colombia): 34 con diagnóstico de FM y 30 controles, a quienes se les realizó evaluación de síntomas psicológicos y de percepción de dolor. Resultados: Los pacientes con FM presentan significativamente mayores síntomas afectivo-conductuales (ansiedad, depresión, insomnio, somatización y disfunción social) que los sujetos controles (p<0.001), así como una tendencia a utilizar la retirada social como estrategia de afrontamiento (p<0.005). De acuerdo con el análisis factorial, la percepción de dolor y los síntomas afectivo-conductuales en pacientes con FM se agruparon en un mismo factor, lo cual demostró interdependencia de las variables. Conclusiones: Los síntomas afectivo-conductuales se asocian a la percepción de dolor y se relacionan con la utilización de estrategias pasivas y centradas en la emoción como mecanismo para afrontar la experiencia de dolor.

Abstract Objective: Fibromyalgia (FM) is a syndrome of chronic widespread pain associated with emotional and behavioral disorders. The purpose of the study was to identify the affective -behavioral symptoms and cognitive coping strategies involved in the perception of pain in patients with FM. Material and methods: A cross-sectional study was performed, with analysis of cases and controls, with a sample of two groups of women, in the city of Barranquilla (Colombia). Affective - behavioral symptoms and cognitive coping strategies were assessed in 34 patients with FM and 30 controls matched by age and educational level. Results: Our findings indicate greater affective and behavioral symptoms in patients with FM (anxiety, depression, insomnia, somatization and social dysfunction) (p<0.001) and a tendency to use social withdrawal as a coping strategy (p<0.005). According to factor analysis, pain perception and affective-behavioral symptoms were grouped in a single factor, demonstrating interdependence between variables. Conclusions: The affective-behavioral symptoms are associated with perception of pain and are relate to the use of passive strategies, and focused on emotion as a mechanism to confront the experience of pain.

Evidence of Structure-Performance Relation for Surfactants Used as Antiagglomerants for Hydrate Management.

Molecular dynamics simulations were employed to study the structure of molecularly thin films of antiagglomerants adsorbed at the interface between sII methane hydrates and a liquid hydrocarbon. The liquid hydrocarbon was composed of dissolved methane and higher-molecular-weight alkane such as n-hexane, n-octane, and n-dodecane. The antiagglomerants considered were surface-active compounds with three hydrophobic tails and a complex hydrophilic head that contains both amide and tertiary ammonium cation groups. The length of the hydrophobic tails and the surface density of the compounds were changed systematically. The results were analyzed in terms of the preferential orientation of the antiagglomerants, density distributions of various molecular compounds, and other molecular-level properties. At low surface densities, the hydrophobic tails do not show preferred orientation, irrespectively of the tail length. At sufficiently high surface densities, our simulations show pronounced differences in the structure of the interfacial film depending on the molecular features and on the type of hydrocarbons present in the system. Some antiagglomerants are found to pack densely at the interface and exclude methane from the interfacial region. Under these conditions, the antiagglomerant film resembles a frozen interface. The hydrophobic tails of the antiagglomerants that show this feature has a length comparable to that of the n-dodecane in the liquid phase. It is possible that the structured interfacial layer is in part responsible for determining the performance of antiagglomerants in flow-assurance applications. The simulation results are compared against experimental data obtained with the rocking cell apparatus. It was found that the antiagglomerants for which our simulations suggest evidence of a frozen interface at sufficiently high surface densities are those that show better performance in rocking cell experiments.

Molecular mechanisms responsible for hydrate anti-agglomerant performance.

Steered and equilibrium molecular dynamics simulations were employed to study the coalescence of a sI hydrate particle and a water droplet within a hydrocarbon mixture. The size of both the hydrate particle and the water droplet is comparable to that of the aqueous core in reverse micelles. The simulations were repeated in the presence of various quaternary ammonium chloride surfactants. We investigated the effects due to different groups on the quaternary head group (e.g. methyl vs. butyl groups), as well as different hydrophobic tail lengths (e.g. n-hexadecyl vs. n-dodecyl tails) on the surfactants' ability to prevent coalescence. Visual inspection of sequences of simulation snapshots indicates that when the water droplet is not covered by surfactants it is more likely to approach the hydrate particle, penetrate the protective surfactant film, reach the hydrate surface, and coalesce with the hydrate than when surfactants are present on both surfaces. Force-distance profiles obtained from steered molecular dynamics simulations and free energy profiles obtained from umbrella sampling suggest that surfactants with butyl tripods on the quaternary head group and hydrophobic tails with size similar to the solvent molecules can act as effective anti-agglomerants. These results qualitatively agree with macroscopic experimental observations. The simulation results provide additional insights, which could be useful in flow assurance applications: the butyl tripod provides adhesion between surfactants and hydrates; when the length of the surfactant tail is compatible with that of the hydrocarbon in the liquid phase a protective film can form on the hydrate; however, once a molecularly thin chain of water molecules forms through the anti-agglomerant film, connecting the water droplet and the hydrate, water flows to the hydrate and coalescence is inevitable.

Telorragia en el lactante / Nipple discharge in an infant

A pesar de constituir la ectasia ductal la causa que con mayor frecuencia ocasiona sangrado a través del pezón en neonatos y lactantes, por la rareza de esta entidad, no deja de sorprender y agobiar a quienes la constatan. Se presenta un lactante masculino, de 8 semanas de nacido, cuyos padres acuden a la Consulta de Endocrinología por sangrado por ambos pezones. Ambas mamas, areolas y pezones mostraban características normales, solamente se halló sangrado con la presión, y el resto del examen físico no mostró alteraciones. La ecografía mamaria fue normal y el estudio citológico confirmó el diagnóstico de ectasia ductal primaria. En el paciente el sangrado cedió espontáneamente con resolución completa en varias semanas. Actualmente, con 3años y 8 meses de edad, no ha presentado nuevas manifestaciones. Por la rareza de su presentación en recién nacidos y lactantes, son muy escasos los informes de esta entidad en la literatura médica, y hasta el momento no hemos encontrado otras descripciones de esta infrecuente enfermedad en artículos nacionales cubanos, lo que motivó la presentación de este caso clínico(AU)

Despite the fact that duct ectasia is the most common cause of bloody nipple discharge in neonates and infants, this rare entity still surprises and causes stress on those who observe it. A male 8 weeks-old patient was presented. His parents took him to the endocrinology service because his two nipples were bleeding. His breasts, areolae, and nipples showed normal characteristics, just bleeding when squeezed; the physical exam did not show any alteration. The breast echography was normal and the cytological study confirmed the diagnosis of primary duct ectasia. The bleeding ceased spontaneously and he completely recovered after several weeks. At present, the patient is 3 years and 8 months-old and does not show any new manifestation. Due to the rareness of this illness in neonates and infants, data are very incomplete in medical literature. Other descriptions of this uncommon disease have not been found in the Cuban national literature, so this encouraged us to present this clinical case(AU)

Removal of atrazine from water using covalent sequestration.

Monochlorotriazines including atrazine and its major metabolites, deethylatrazine and deisopropylatrazine, are susceptible to nucleophilic aromatic substitution. Competitive reactions to rank the relative reactivity of nucleophiles with atrazine reveal that constrained secondary amines are the most reactive. When the nucleophile is attached to a solid support, atrazine can be sequestered from solution. As proof of concept, polystyrene resins displaying constrained secondary amines are shown to sequester atrazine, deethylatrazine, and deisopropylatrazine from water. Sequestration can be followed spectrophotometrically or using a liquid chromatography mass spectrometry protocol. The kinetics of sequestration are similar to that of granulated charcoal. Evidence for covalent bond formation comes from control experiments with unreactive herbicides and degradation analysis of the solid support. Using both (1)H NMR spectroscopy and mass spectrometry, covalent adducts are identified in ratios close to what is calculated theoretically. This method for sequestration is effective at removing atrazine from pond water.

Enfermedad metastásica de hígado. Enfoque quirúrgico / Liver metastasis: Surgical perspective

Aproximadamente la mitad de los pacientes con carcinoma colorrectal desarrollan mestástasis y de éstos, aproximadamente el 10 por ciento es posible tratarlos quirúrgicamente. El tratamiento quirúrgico (resectivo) es actualmente la primera opción terapéutica para los tumores metastásicos del hígado. Se obtiene una sobrevida del 20 al 40 por ciento a cinco años. La evaluación preoperatoria es crítica y se hace fundamentalmente con métodos de imagen. El mejor resultado se obtiene en pacientes con metástasis únicas, en las cuales es posible la resección total de la lesión (®curativa¼). Los factores que afectan negativamente las resecciones son: más de cuatro lesiones, margen quirúrgico menor a 1 cm. Además de estos tumores, las metástasis de tumores neuroendocrinos son susceptibles de este tipo de tratamiento, siendo necesaria la individualización de cada caso. Esta conducta es aplicable también para otro tipo de metástasis. Los tratamientos adyuvantes como la quimioembolización y/o quimioterapia intraarterial, pueden tener valor terapéutico al igual que la crioterapia