Polysaccharide Hydroxyapatite (Nano)composites and Their Biomedical Applications: An Overview of Recent Years.

Hydroxyapatite can combine with polysaccharide originating biomaterials with special applications in the biomedical field. In this review, the synthesis of (nano)composites is discussed, focusing on natural polysaccharides such as alginate, chitosan, and pectin. In this way, advances in recent years in the development of preparing materials are revised and discussed. Therefore, an overview of the recent synthesis and applications of polyssacharides@hydroxyapatites is presented. Several studies based on chitosan@hydroxyapatite combined with other inorganic matrices are highlighted, while pectin@hydroxyapatite is present in a smaller number of reports. Biomedical applications as drug carriers, adsorbents, and bone implants are discussed, combining their dependence with the nature of interactions on the molecular scale and the type of polysaccharides used, which is a relevant aspect to be explored.

Sleep duration, overweight status, and the modifying role of food insecurity in a sample of 10- to 14-year-old Mexican early adolescents.

OBJECTIVES: Short sleep duration has been associated with an increased risk of childhood overweight and obesity in high-income countries, but data from low- and middle-income countries are scarce. Independently, short sleep and food insecurity may increase the risk of overweight/obesity, but it is unknown whether they concurrently affect it. METHODS: We included 3350 adolescents aged 10-14 from the 2012 and 2016 Mexican National Health and Nutrition Survey. Short sleep was categorized as less than 9 hours for ages 10-12 and less than 8 hours for ages 13-14. Overweight/obesity was assessed via anthropometry. Modified Poisson regression models assessed prevalence ratios between short sleep and overweight, examining effect modification by food security status. RESULTS: 86% met sleep duration recommendations. Short sleep was associated with an increased prevalence of overweight/obesity (prevalence ratio, 1.16; 95% CI, 1.05, 1.31). Multiplicative interaction was found between low and very low food security status and short sleep: adolescents in low food secure households with short sleep had 1.38 (95% CI: 1.10, 1.75) times the prevalence of overweight/obesity compared to adequate sleepers. Very low food secure households had 1.16 (95% CI: 1.14, 1.31) times the prevalence compared to adequate sleepers. This association was not significant in fully or marginally food secure households. CONCLUSIONS: Short sleep is associated with an increased obesity risk among Mexican adolescents 10-14years, particularly in the context of low and very low food security. These findings highlight the importance of addressing both sleep hygiene and food security in strategies to reduce obesity risk.

Functional Technical Textile-Based Polymer Nanocomposites with Adsorbent Properties of Toxins and Dyes also Have Antibacterial Behavior.

This is the first study of non-woven fabrics elaborated by melt-blowing from polymer nanocomposites made of Nylon 6 and nanoclay (Cloisite 20A) modified with an amine (1,4 diaminobutane dihydrochloride). Morphological and physical characteristics, adsorption capacity, and antibacterial properties are presented. From the X-ray diffraction (XRD) results, it was possible to observe a displacement of the signals to other 2θ angles, due to an α to ϒ phase shift. The scanning electron microscopy (SEM) images showed that the mean diameter of fiber decreased as the content of nanoclay increased. The mechanical tests showed that the tear strength force of neat nylon was 1.734 N, but this characteristic increased to 2.135 N for the sample with 0.5% modified nanoclay. The inulin adsorption efficiency of the Nylon 6/C20A 1.5% and Nylon 6/C20A 2% samples at 15 min was 75 and 74%, respectively. The adsorption capacity of Nylon 6/C20A 1.5% and Nylon 6/C20A 2% for methylene blue and methyl orange remained above 90% even after four adsorption cycles. In addition, non-woven fabrics present antibacterial activity against E. coli.

Update of the guidelines for the pharmacological treatment of rheumatoid arthritis by the Mexican College of Rheumatology 2023.

OBJECTIVE: To develop updated guidelines for the pharmacological management of rheumatoid arthritis (RA). METHODS: A group of experts representative of different geographical regions and various medical services catering to the Mexican population with RA was formed. Questions based on Population, Intervention, Comparison, and Outcome (PICO) were developed, deemed clinically relevant. These questions were answered based on the results of a recent systematic literature review (SLR), and the evidence's validity was assessed using the GRADE system, considered a standard for these purposes. Subsequently, the expert group reached consensus on the direction and strength of recommendations through a multi-stage voting process. RESULTS: The updated guidelines for RA treatment stratify various therapeutic options, including different classes of DMARDs (conventional, biologicals, and JAK inhibitors), as well as NSAIDs, glucocorticoids, and analgesics. By consensus, it establishes the use of these in different subpopulations of interest among RA patients and addresses aspects related to vaccination, COVID-19, surgery, pregnancy and lactation, and others. CONCLUSIONS: This update of the Mexican guidelines for the pharmacological treatment of RA provides reference points for evidence-based decision-making, recommending patient participation in joint decision-making to achieve the greatest benefit for our patients. It also establishes recommendations for managing a variety of relevant conditions affecting our patients.

Risk factors for hospitalization in Mexican patients with systemic lupus erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease that often requires hospitalization. Most hospitalizations are due to infections and/or disease activity, for which several risk factors have been described in non-Mestizo patients. OBJECTIVE: To identify risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). METHODS: This was an observational case-control study of patients with SLE in San Luis Potosí, Mexico, evaluated from January 2019 to October 2020. We compared hospitalized lupus patients with non-hospitalized lupus patients. We used descriptive statistics and logistic regression to describe potential risk factors. RESULTS: Of a total of 202 patients, 89 (45.1%) were hospitalized; these patients were younger, had shorter disease duration, higher disease activity scores (systemic lupus erythematosus disease activity index-SLEDAI), and more accumulated damage than non-hospitalized patients. The primary reasons for hospitalization were disease activity (60.7%), kidney disease, infection, and drug toxicity (5.6%). Multivariate analysis revealed several risk factors associated with hospitalization, including elevated creatinine, C-reactive protein, neutrophil levels, and constitutional symptoms, while prolonged international normalized ratio (INR), longer stay in the intensive care unit (ICU), and vasopressor use were associated with mortality. The use of antimalarials was a protective factor against hospitalization. Survival analysis revealed that patients with hospital-acquired infections had a lower probability of survival. CONCLUSIONS: Disease activity was the most common reason for hospitalization; kidney, constitutional, and hematological factors were associated with hospitalization; and the use of antimalarial was a protective factor for hospitalization.

Impact of hydrocarbon extraction on heavy metal concentrations in lowland paca (Cuniculus paca) from the Peruvian Amazon.

Oil has been extracted from the Western Amazon since the 1920s, leading to severe environmental contamination due to frequent occurrence oil spills and the dumping of produced water. Local inhabitants, along with environmental and human rights organizations, have reported the adverse effects of oil-related pollution on their livelihoods and the ecosystems they depend on. Here, we study accumulation of oil-related heavy metals in wildlife, and its subsequent incorporation into the trophic chain. We analysed the concentration of 14 heavy metals (Cd, Cr, Hg, As, Ni, V, Ba, Se, Be, Fe, Cu, Zn, Mn, Al) in liver samples from 78 lowland pacas (Cuniculus paca) hunted for subsistence in an oil-polluted area from the northern Peruvian Amazon where oil has been extracted since the 1970s (n = 38), and two control areas, the Yavari-Mirín River basin (n = 20), and the Pucacuro River basin (n = 20). Pacas in the oil-polluted area have significantly higher concentrations of Cd (P < 0.01) and Ba (P < 0.0001) compared to those in control areas, suggesting bioaccumulation of oil-related pollution. Conversely, Se levels were significantly lower in the oil-polluted area (P < 0.0001), likely due to the sequestration of Se by other heavy metals, particularly Cd. Additionally, minor variations in other heavy metals, e.g., Fe and Zn, were observed in pacas from the oil-polluted area, whereas control areas showed higher concentrations of Ni and Cu. Mn and Al levels did not significantly differ between the study areas. These results underscore the impact of oil extraction on the absorption and assimilation of heavy metals in wildlife, point at oil activities as the source of the high and unsafe blood Cd levels reported for the indigenous population of the studied oil extraction area and raise concerns about the long-term health risks from oil extraction posed to local Indigenous People who rely on subsistence hunting.

Synthesis and Characterization of Cassava Gum Hydrogel Associated with Chlorhexidine and Evaluation of Release and Antimicrobial Activity.

Hydrogels from natural sources are attracting increasing interest due to their ability to protect biologically active molecules. Starch extracted from cassava tubers is a promising material for synthesizing these hydrogels. Copolymerization of cassava gum and incorporation of chlorhexidine digluconate (CLX) into the hydrogels is confirmed by changes in the crystallographic profile, as observed through X-ray diffraction, and a shift in the 1000 cm-1 band in the Fourier-transform infrared spectroscopy spectrum. The differential scanning calorimetry reveals changes in the decomposition temperature of the synthesized hydrogels related to CLX volatility. Micrographs illustrate the material's porosity. Release tests indicate a constant linear release over 72 h, while antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans is satisfactory, with 100% effectiveness from 0.5% CLX and the formation of inhibition halos. Toxicity and biocompatibility studies show no cytotoxicity. The continuous release of chlorhexidine is promising for components of biomedical implants and applications as it can ensure antimicrobial action according to specific therapeutic needs.

Stevia rebaudiana Bertoni, an American plant used as sweetener: Study of its effects on body mass control and glycemia reduction in Wistar male and female rats.

Stevia rebaudiana Bertoni water extracts have been used as a natural sweetener and customary medicine by the indigenous inhabitants of South America for several hundred years. This plant was sent to Europe in the 16th century and was described by Peter Jacob Esteve in Spain. Recently the food industry has started to employ S. rebaudiana as sweetener using its glycosides after purification. Advertisement claims that Stevia glycosides is good for controling body mass and reducing glycemia. This study's objective was to evaluate the effect of S. rebaudiana leaf extract on Wistar rats as animal model to prove its effectiveness on body mass control, glycemia reduction, and other biochemical parameters. Three groups were randomly formed with 24 males and 24 females: A blank group without any sweetener, a control group drinking water with 10% glucose, and the test group ingesting a 0.94% water extract of S. rebaudiana. Body mass measurements as well as food and drink consumption were daily performed. The experiment lasted 120 days after the specimens were weaned and got used to eating solid food. Euthanasia was done and blood serum was collected to evaluate the following biochemical parameters: Glucose, triglycerides, cholesterol, insulin, glucagon, leptin, ghrelin, and glucose-dependent insulinotropic peptide, GIP. Results indicated that only female rats had statistical differences in body mass gain. No relevant effects either positive or negative were found in the biochemical parameters measured. The crude extracts of S. rebaudiana did not show any relevant changes in biochemical and hormonal profiles, changes nor body mass with respect to the blank and control groups of young and healthy rats in the age range of infancy to youth. According to the results obtained, the therapeutic properties that have been associated to S. rebaudiana consumption especially for body mass control and glycemia reduction, did not occur in young and healthy male and female rats in equivalent age to infants, young children, and youths.

Influenza A virus antibodies in dogs, hunting dogs, and backyard pigs in Campeche, Mexico.

AIMS: This study aimed to identify exposure to human, swine, and avian influenza A virus subtypes in rural companion and hunting dogs, backyard pigs, and feral pigs. METHODS AND RESULTS: The study took place in a region of southeastern Mexico where the sampled individuals were part of backyard production systems in which different domestic and wild species coexist and interact with humans. We collected blood samples from pigs and dogs at each of the sites. We used a nucleoprotein enzyme-linked immunosorbent assay to determine the exposure of individuals to influenza A virus. Haemagglutination inhibition was performed on the positive samples to determine the subtypes to which they were exposed. For data analysis, a binomial logistic regression model was generated to determine the predictor variables for the seropositivity of the individuals in the study. We identified 11 positive individuals: three backyard pigs, four companion dogs, and four hunting dogs. The pigs tested positive for H1N1 and H1N2. The dogs were positive for H1N1, H1N2, and H3N2. The model showed that dogs in contact with backyard chickens are more likely to be seropositive for influenza A viruses. CONCLUSIONS: We demonstrated the essential role hunting dogs could play as intermediate hosts and potential mixing vessel hosts when exposed to human and swine-origin viral subtypes. These results are relevant because these dogs interact with domestic hosts and humans in backyard systems, which are risk scenarios in the transmission of influenza A viruses. Therefore, it is of utmost importance to implement epidemiological surveillance of influenza A viruses in backyard animals, particularly in key animals in the transmission of these viruses, such as dogs and pigs.

Advancing Alzheimer's Therapeutics: Exploring the Impact of Physical Exercise in Animal Models and Patients.

Alzheimer's disease (AD) is the main neurodegenerative disorder characterized by several pathophysiological features, including the misfolding of the tau protein and the amyloid beta (Aß) peptide, neuroinflammation, oxidative stress, synaptic dysfunction, metabolic alterations, and cognitive impairment. These mechanisms collectively contribute to neurodegeneration, necessitating the exploration of therapeutic approaches with multiple targets. Physical exercise has emerged as a promising non-pharmacological intervention for AD, with demonstrated effects on promoting neurogenesis, activating neurotrophic factors, reducing Aß aggregates, minimizing the formation of neurofibrillary tangles (NFTs), dampening inflammatory processes, mitigating oxidative stress, and improving the functionality of the neurovascular unit (NVU). Overall, the neuroprotective effects of exercise are not singular, but are multi-targets. Numerous studies have investigated physical exercise's potential in both AD patients and animal models, employing various exercise protocols to elucidate the underlying neurobiological mechanisms and effects. The objective of this review is to analyze the neurological therapeutic effects of these exercise protocols in animal models and compare them with studies conducted in AD patients. By translating findings from different approaches, this review aims to identify opportune, specific, and personalized therapeutic windows, thus advancing research on the use of physical exercise with AD patients.

[Subtle and subclinical neurological findings in patients with SARS-CoV-2]. / Hallazgos sutiles y subclínicos neurológicos en pacientes con SARS-CoV-2.

Background: There are severe neurological conditions in patients with COVID-19, such as: cerebrovascular disease, Guillain-Barré syndrome, encephalitis, acute hemorrhagic necrotizing encephalopathy and myelitis. Objective: We describe that the patient with SARS-CoV 2 with respiratory symptoms has subtle or subclinical neurological manifestations. Material and methods: Observational, cross-sectional, analytical study, which included patients aged 18-65 years with respiratory symptoms and a confirmed diagnosis of COVID-19. Intubated patients with chronic neurodegenerative diseases or pre-existing neurological compromise were excluded. Semiology of the headache and neurological examination were performed; Serum levels of glucose, protein, electrolytes, lactate, C-reactive protein, lactic dehydrogenase, and D-dimer were measured. Cerebrospinal fluid (CSF) analysis and electroencephalogram (EEG) were also performed in patients who accepted the risks. Results: A high prevalence of subtle neurological manifestations was found in patients with COVID-19 with only a respiratory clinical picture. Headache, anosmia, dysgeusia, and hypopalesthesia predominated in the early stages, with frequent abnormal findings in the CSF (>70%) and less frequently in the EEG (<20%). Conclusions: Headache, anosmia, dysgeusia and hypoesthesia were frequent at the beginning of the infection, together with abnormal findings in CSF and EEG, without other neurological symptoms or neurological disease.

Introducción: existen condiciones neurológicas severas en pacientes con COVID-19, como: enfermedad cerebrovascular, síndrome de Guillain-Barré, encefalitis, encefalopatía necrotizante hemorrágica aguda y mielitis. Objetivo: describimos que el paciente con SARS-CoV-2 con síntomas respiratorios tiene manifestaciones neurológicas sutiles o subclínicas. Material y métodos: estudio observacional, transversal, analítico, que incluyó pacientes de 18-65 años con síntomas respiratorios y diagnóstico de COVID-19 confirmado. Se excluyeron pacientes intubados, con enfermedades neurodegenerativas crónicas o compromiso neurológico preexistente. Se realizó semiología de la cefalea y exploración neurológica; Se midieron los niveles séricos de glucosa, proteínas, electrolitos, lactato, proteína C reactiva, deshidrogenasa láctica y dímero D. También se realizaron análisis de líquido cefalorraquídeo (LCR) y un electroencefalograma (EEG) en los pacientes que aceptaron los riesgos. Resultados: se encontró alta prevalencia de manifestaciones neurológicas sutiles en pacientes con COVID-19 con solo cuadro clínico respiratorio. Cefalea, anosmia, disgeusia e hipopalestesia predominaron en las primeras etapas, con hallazgos anormales frecuentes en el LCR (>70%) y con menos frecuencia en el EEG (<20%). Conclusiones: la cefalea, anosmia, disgeusia e hipoestesia fueron frecuentes al inicio de la infección, junto con hallazgos anormales en LCR y EEG, sin otros síntomas neurológicos ni enfermedad neurológica.

Effects of Voluntary Physical Exercise on the Neurovascular Unit in a Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Histopathologically, AD presents two pathognomonic hallmarks: (1) neurofibrillary tangles, characterized by intracellular deposits of hyperphosphorylated tau protein, and (2) extracellular amyloid deposits (amyloid plaques) in the brain vasculature (cerebral amyloid angiopathy; CAA). It has been proposed that vascular amyloid deposits could trigger neurovascular unit (NVU) dysfunction in AD. The NVU is composed primarily of astrocytic feet, endothelial cells, pericytes, and basement membrane. Although physical exercise is hypothesized to have beneficial effects against AD, it is unknown whether its positive effects extend to ameliorating CAA and improving the physiology of the NVU. We used the triple transgenic animal model for AD (3xTg-AD) at 13 months old and analyzed through behavioral and histological assays, the effect of voluntary physical exercise on cognitive functions, amyloid angiopathy, and the NVU. Our results show that 3xTg-AD mice develop vascular amyloid deposits which correlate with cognitive deficits and NVU alteration. Interestingly, the physical exercise regimen decreases amyloid angiopathy and correlates with an improvement in cognitive function as well as in the underlying integrity of the NVU components. Physical exercise could represent a key therapeutic approach in cerebral amyloid angiopathy and NVU stability in AD patients.

A Deep Learning Approach for Predicting Multiple Sclerosis.

This paper proposes a deep learning model based on an artificial neural network with a single hidden layer for predicting the diagnosis of multiple sclerosis. The hidden layer includes a regularization term that prevents overfitting and reduces the model complexity. The purposed learning model achieved higher prediction accuracy and lower loss than four conventional machine learning techniques. A dimensionality reduction method was used to select the most relevant features from 74 gene expression profiles for training the learning models. The analysis of variance test was performed to identify the statistical difference between the mean of the proposed model and the compared classifiers. The experimental results show the effectiveness of the proposed artificial neural network.

Microalgal consortium tolerance to bisphenol A and triclosan in wastewater and their effects on growth, biomolecule content and nutrient removal.

Amongst the many treatments available for the removal of emerging contaminants in wastewater, microalgal cultures have been shown to be effective. However, the effectiveness of exposure of a native microalgal consortium to emerging contaminants such as bisphenol-A (BPA) and triclosan (TCS) to determine the half-maximum effective concentrations (EC50) has not yet been determined. The effect on growth and nutrient removal of such a treatment as well as on the production of biomolecules such as carbohydrates, lipids, and proteins are, at present, unknown. In this study, the EC50 of BPA and TCS (96-hour experiments) was determined using a consortium of native microalgae (Scenedesmus obliquus and Desmodesmus sp.) to define the maximum tolerance to these contaminants. The effect of BPA and TCS in synthetic wastewater (SWW) was investigated in terms of microalgal growth, chlorophyll a (Chl-a), carbohydrate, lipid, and protein content, as well as nutrient removal. Assays were performed in heterotrophic conditions (12/12 light/dark cycles). EC50-96 h values of 17 mg/L and 325 µg/L for BPA and TCS, respectively, were found at 72 h. For an initial microalgal inoculum of ≈ 300 mg TSS/L (total suspended solids per litre), growth increased by 16.1% when exposed to BPA and 17.78% for TCS. At ≈ 500 mg TSS/L, growth increased by 8.25% with BPA and 9.92% with TCS, respectively. At the EC50-96 h concentrations determined in the study, BPA and TCS did not limit the growth of microalgae in wastewater. Moreover, they were found to stimulate the content of Chl-a, carbohydrates, lipids, proteins, and enhance nutrient removal. AVAILABILITY OF DATA AND MATERIAL: Data sharing not applicable to this article as no datasets were generated or analysed during the present study.

PLA/modified-starch blends and their application for the fabrication of non-woven fabrics by melt-blowing.

Blends of polylactic acid (PLA) and thermoplastic starch (TS) with and without chemical modification were obtained by melt extrusion and used to obtain non-woven fabrics by melt-blowing for the first time. Different TS were obtained by reactive extrusion from native cassava, oxidized, maleated, and dual modified (oxidized and maleated) starch. The chemical modification of starch decreases the difference in viscosity and favors blending, resulting in more homogeneous morphologies, unlike the blends with unmodified TS, which displayed a visible phase separation with large TS droplets. The dual modified starch showed a synergistic effect to process TS by melt-blowing. Regarding non-woven fabrics, values in diameter (2.5-82.1 µm), thickness (0.4-0.6 mm), and grammage (49.9-103.8 g/m2) were explained due to differences in viscosity of the components, and to the fact that during melt the hot air preferentially stretches and thins the areas without large droplets of TS. Moreover, plasticized starch acts as a flow modifier. The porosity of the fibers increased with the addition of TS. Further studies and optimization of blends with low contents of TS and type starch modification will be necessary to completely understand these systems with very complex behavior to obtain non-woven fabrics with improved properties and application.

Aberraciones corneales en pacientes con indicación de cirugía refractiva con láser de excímeros / Corneal Aberrations of Patients Indicated for Excimer Laser Refractive Surgery

Objetivo: Determinar las aberraciones corneales en pacientes con indicación de cirugía refractiva con láser de excímeros. Métodos: Se realizó un estudio retrospectivo, transversal, descriptivo, con 161 ojos de 81 pacientes adultos, de ambos sexos con indicación de cirugía con láser de excímeros para la corrección de su defecto refractivo. Se definieron como variables edad, sexo, desenfoque, astigmatismo, coma, trefoil y aberración esférica, las que se determinaron por el estudio topográfico de rutina con el topógrafo KeratronTM Scout, Optikon. Resultados: Se obtuvieron los siguientes valores promedios: desenfoque -4,17 ± 0,29 D (-16,15 a 8,5 D) y absoluto 4,94 ± 0,199 (10 a 16,5 D), astigmatismo -1,56 ± 0,09 D (-9,44 a -0,09 D), coma 0,25 ± 0,016 (0,01 a 1,5 D), trefoil 0,204 ± 0,016 (0,01 a 1,18 D) y aberración esférica 0,316 ± 0,018 D (0,0 a 1,27D). En el 75 por ciento de los casos los valores absolutos de desenfoque fueron inferiores a 6,56, de astigmatismo inferior a 0,33 D, de coma menor que 0,33, trefoil inferior a 0,25 y aberraciones esféricas menores que 0,32 D. Conclusiones: Los valores promedio de las aberraciones corneales desenfoque, astigmatismo, coma, trefoil y aberración esférica se encuentran en el rango de los valores reportados en la literatura científica y la distribución de los valores de las aberraciones corneales presentan desplazamiento de la mayoría de los casos hacia los valores más bajo del rango de determinación(AU)

Objective: To determine corneal aberrations in patients indicated for excimer laser refractive surgery. Methods: A retrospective, cross-sectional and descriptive study was carried out with 161 eyes of 81 adult patients of both sexes with indication of excimer laser surgery for the correction of their refractive defect. Age, sex, defocus, astigmatism, coma, trefoil and spherical aberration were defined as variables, determined by routine topographic study with the KeratronTM Scout topographer, Optikon. Results: The following average values were obtained: defocus of -4.17 ± 0.29 D (-16.15 to 8.5 D) and absolute of 4.94 ± 0.199 (10 to 16.5 D), astigmatism of -1.56 ± 0.09 D (-9.44 to -0.09 D), coma of 0.25 ± 0.016 (0.01 to 1.5 D), trefoil of 0.204 ± 0.016 (0.01 to 1.18 D) and spherical aberration of 0.316 ± 0.018 D (0.0 to 1.27D). In 75 percent of the cases, the absolute values for defocus were lower than 6.56; for astigmatism, lower than 0.33 D; for coma, lower than 0.33; for trefoil, lower than 0.25; and for spherical aberrations, lower than 0.32 D. Conclusions: The average values of corneal aberrations for defocus, astigmatism, coma, trefoil and spherical aberration are in the range of values reported in the scientific literature, while the distribution of corneal aberrations values present displacement of most of the cases towards the lower values of the determination range(AU)