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Abstract Chiari disease (or malformation) is in general a congenital condition characterized by an anatomic defect of the base of the skull, in which the cerebellum and brain stem herniate through the foramen magnum into the cervical spinal canal. The onset of Chiari syndrome symptoms usually occurs in the second or third decade (age 25 to 45 years). Symptoms may vary between periods of exacerbation and remission. The diagnosis of Chiari type I malformation in patients with or without symptoms is established with neuroimaging techniques. The most effective therapy for patients with Chiari type I malformation/syringomyelia is surgical decompression of the foramen magnum, however there are non-surgical therapy to relieve neurophatic pain: either pharmacological and non-pharmacological. Pharmacological therapy use drugs that act on different components of pain. Non-pharmacological therapies are primarly based on spinal or peripheral electrical stimulation. It is important to determine the needs of the patients in terms of health-care, social, educational, occupational, and relationship issues, in addition to those derived from information aspects, particularly at onset of symptoms. Currently, there is no consensus among the specialists regarding the etiology of the disease or how to approach, monitor, follow-up, and treat the condition. It is necessary that the physicians involved in the care of people with this condition comprehensively approach the management and follow-up of the patients, and that they organize interdisciplinary teams including all the professionals that can help to increase the quality of life of patients.

Abstract Chronic fatigue syndrome is characterised by intense fatigue, with duration of over six months and associated to other related symptoms. The latter include asthenia and easily induced tiredness that is not recovered after a night's sleep. The fatigue becomes so severe that it forces a 50% reduction in daily activities. Given its unknown aetiology, different hypotheses have been considered to explain the origin of the condition (from immunological disorders to the presence of post-traumatic oxidative stress), although there are no conclusive diagnostic tests. Diagnosis is established through the exclusion of other diseases causing fatigue. This syndrome is rare in childhood and adolescence, although the fatigue symptom per se is quite common in paediatric patients. Currently, no curative treatment exists for patients with chronic fatigue syndrome. The therapeutic approach to this syndrome requires a combination of different therapeutic modalities. The specific characteristics of the symptomatology of patients with chronic fatigue require a rapid adaptation of the educational, healthcare and social systems to prevent the problems derived from current systems. Such patients require multidisciplinary management due to the multiple and different issues affecting them. This document was realized by one of the Interdisciplinary Work Groups from the Institute for Rare Diseases, and its aim is to point out the main social and care needs for people affected with Chronic Fatigue Syndrome. For this, it includes not only the view of representatives for different scientific societies, but also the patient associations view, because they know the true history of their social and sanitary needs. In an interdisciplinary approach, this work also reviews the principal scientific, medical, socio-sanitary and psychological aspects of Chronic Fatigue Syndrome.

ABSTRACT Background Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting. Methods The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained. Results Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased. Conclusions In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage.

In recent decades, there has been an increase in the identification of thyroid nodules, both benign and malignant, due to the rise in imaging studies and complementary tests. Among thyroid gland tumors, papillary thyroid carcinoma (PTC) stands out as the most prevalent. Degenerative changes, mainly in the form of nodular goiter, have been recorded, occasionally including areas of calcification and, more rarely, ossification; although the latter seldom progresses to calcinosis. Ectopic bone formation, known as osseous metaplasia, is a rare phenomenon in the thyroid gland, even more so when associated with extramedullary hematopoiesis (EMH), characterized by the presence of hematopoietic elements outside the bone marrow. We present the first documented instance in our country of a patient diagnosed with malignant thyroid nodule, specifically PTC, exhibiting areas of heterotopic ossification with EMH on histopathological examination of the surgical specimen. A possible relationship between heterotopic ossification, EMH, and PTC is suggested. Various growth factors such as bone morphogenetic proteins (BMPs), specific BMP subtypes, and associated receptors could play a crucial role in initiating and developing ectopic bone formation in the context of PTC. However, further research is needed to fully elucidate its clinical significance and impact on the therapeutic management of these patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To evaluate the visual outcome, light distortion index (LDI), and quality of life (QoL) of patients implanted with two complementary intraocular lenses (IOLs) to treat cataract and presbyopia., Methods: Twenty-seven consecutive patients with cataract were treated with the implantation of the Artis Symbiose Mid (Mid) IOL (Cristalens Industrie) in the distance-dominant eye and the Artis Symbiose Plus (Plus) IOL (Cristalens Industrie) in the contralateral eye following phacoemulsification. The primary objective was to ascertain the monocular and binocular defocus curves. Secondary endpoints included uncorrected distance visual acuity, corrected distance visual acuity, uncorrected intermediate visual acuity, and distance-corrected intermediate visual acuity at 90 and 70 cm, uncorrected near visual acuity and distance-corrected visual acuity at 40 cm, contrast sensitivity, LDI with a halometer, stereopsis, and patients' QoL with the validated Visual Function Index (VF-14) questionnaire. These measurements were collected in two visits, at 4.14 ± 3.13 and 10.30 ± 3.14 months postoperatively., Results: Statistically significant differences in the monocular defocus curves were found at the defocus steps of -1.00, -1.25, -1.50, -1.75, -2.50, -2.75, -3.00, -3.50 diopters and the -4.00 diopters ( P < .050). The mean binocular defocus curve was 0 logMAR or better from the +0.50 to the -2.50 D defocus steps. Contrast sensitivity was within normal values. The LDI was 12.57 (6.61)% for the Mid eyes, 14.99 ± 5.70% for the Plus eyes, and 10.36 ± 4.42% binocularly. The patients' stereopsis was 40.0 (12.5) arc-seconds. The QoL score was 95.99 (7.14) at 10 months., Conclusions: The implantation of the Artis Symbiose IOLs was a safe and effective treatment for presbyopia compensation in patients with cataract. Both IOLs are complementary and may produce a binocular depth-of-field of 3.00 diopters over 0 logMAR when used together. [ J Refract Surg . 2023;39(10):654-661.] .

Purpose: To corroborate whether vessels on the surface of the optic nerve head can provide protection against the loss of underlying axons in subjects with manifest glaucoma., Methods: In this pilot study, thirty-six glaucomatous eyes with a perimetric defect in the Bjerrum area were included. The retinal nerve fiber layer (RNFL) thickness was measured in each of the sectors of the clock-hour map obtained by Cirrus HD-OCT considering the presence or absence of blood vessels. These sectors were related with their corresponding areas of the retina examined in the visual field using a mathematical model of the retina introduced by Jansonius, in order to determine the values of threshold sensitivity in those areas in the presence or absence of vessels., Results: We corroborated the protective role of the blood vessel for peripapillary RNFL thickness of clock-hour 12 despite obtaining a p-value (p = 0.023; w = 228.5) close to the acceptance zone (p ≥ 0.05). The mean ± standard deviation with vessel and without vessel were 70.95 ± 24.35 and 88.46 ± 23.96, respectively. No differences were found between the mean values of threshold sensitivity to the presence or absence of blood vessels in each of the sectors considered., Conclusions: Our findings do not allow us to affirm that there is an association between the presence of a vessel and protection against glaucomatous damage in subjects with an advanced manifestation of the disease. In the future, more extensive studies are needed to study this relationship in subjects with early glaucoma., Competing Interests: Conflicts of interests The authors declares that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.)

A new versatile and geometrically reconfigurable ultrasonic tomography system (UTS) has been designed to inspect and obtain information about the internal structure and inner damage of columns in heritage buildings. This nondestructive system is considered innovative because it aims to overcome common limitations of existing systems. Tomographic inspections are typically carried out manually and are thus limited to small portions of construction elements. The proposed UTS allows the automatization of the inspection and the generation of numerous tomographic slices along the height of the column. It is valid for multiple types of columns and materials. In the present work, the system was tested on two limestone columns of the north façade of the Convent of Carmo in Lisbon, Portugal. The UTS is composed of a mechanical and an electronic system. The mechanical system consists of four linear motion subsystems mounted in a square setup. A transducer is placed on each of the axes, acting as emitter or receiver of the ultrasonic signals. The mechanical system also includes a guide system to adapt the inspections to the complex geometry of the columns. The electronic system allows the control and the synchronization of the movements and the emission/reception configuration of the four ultrasonic transducers.

Background: Contextual fear conditioning (CFC) is a rodent model that induces a high and long-lasting level of conditioning associated with traumatic memory formation; this behavioral paradigm resembles many characteristics of posttraumatic stress disorder (PSTD). Chemokines (chemotactic cytokines) play a known role in neuronal migration and neurodegeneration but their role in cognition is not totally elucidated., Aim: We ascertain whether CCR5/RANTES beta chemokines (hippocampus/prefrontal cortex) could play a role in fear memory consolidation (CFC paradigm). We also evaluated whether chronic stress restraint (21 days of restraint, 6-h/day) could regulate levels of these beta chemokines in CFC-trained rats; fear memory retention was determined taking the level of freezing (context and tone) by the animals as an index of fear memory consolidation 24 h after CFC training session; these chemokines (CCR5/RANTES) and IL-6 levels were measured in the hippocampus and prefrontal cortex of chronically stressed rats, 24 h after CFC post-training, and compared with undisturbed CFC-trained rats (Experiment 1). In Experiment 2, rats received 1 mA of footshock during the CFC training session and fear memory consolidation was evaluated at 12 and 24 h after CFC training sessions. We evaluated whether RANTES levels could be differentially regulated at 12 and 24 h after CFC training; in Experiment 3, maraviroc was administered to rats (i.m: 100 mg/Kg, a CCR5 antagonist) before CFC training. These rats were not subjected to chronic stress restraint. We evaluated whether CCR5 blockade before CFC training could increase corticosterone, RANTES, or IL-6 levels and affects fear memory consolidation in the rats 24-h post-testing compared with vehicle CFC-trained rats., Results: Elevations of CCR5/RANTES chemokine levels in the hippocampus could have contributed to fear memory consolidation (24 h post-training) and chronic stress restraint did not affect these chemokines in the hippocampus; there were no significant differences in CCR5/RANTES levels between stressed and control rats in the prefrontal cortex (Experiment 1). In Experiment 2, hippocampal CCR5/RANTES levels increased and enhanced fear memory consolidation was observed 12 and 24 h after CFC training sessions with 1 mA of footshock. Increased corticosterone and CCR5/RANTES levels, as well as a higher freezing percentage to the context, were found at 24 h CFC post-testing in maraviroc-treated rats as compared to vehicle-treated animals (experiment-3). Conversely, IL-6 is not affected by maraviroc treatment in CFC training., Conclusion: Our findings suggest a role for a hippocampal CCR5/RANTES axis in contextual fear memory consolidation; in fact, RANTES levels increased at 12 and 24 h after CFC training. When CCR5 was blocked by maraviroc before CFC training, RANTES (hippocampus), corticosterone levels, and fear memory consolidation were greater than in vehicle CFC-trained rats 24 h after the CFC session., Competing Interests: All authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Type 1 Diabetes Mellitus (DM1) patients are used to checking their blood glucose levels several times per day through finger sticks and, by subjectively handling this information, to try to predict their future glycaemia in order to choose a proper strategy to keep their glucose levels under control, in terms of insulin dosages and other factors. However, recent Internet of Things (IoT) devices and novel biosensors have allowed the continuous collection of the value of the glucose level by means of Continuous Glucose Monitoring (CGM) so that, with the proper Machine Learning (ML) algorithms, glucose evolution can be modeled, thus permitting a forecast of this variable. On the other hand, glycaemia dynamics require that such a model be user-centric and should be recalculated continuously in order to reflect the exact status of the patient, i.e., an 'on-the-fly' approach. In order to avoid, for example, the risk of being disconnected from the Internet, it would be ideal if this task could be performed locally in constrained devices like smartphones, but this would only be feasible if the execution times were fast enough. Therefore, in order to analyze if such a possibility is viable or not, an extensive, passive, CGM study has been carried out with 25 DM1 patients in order to build a solid dataset. Then, some well-known univariate algorithms have been executed in a desktop computer (as a reference) and two constrained devices: a smartphone and a Raspberry Pi, taking into account only past glycaemia data to forecast glucose levels. The results indicate that it is possible to forecast, in a smartphone, a 15-min horizon with a Root Mean Squared Error (RMSE) of 11.65 mg/dL in just 16.15 s, employing a 10-min sampling of the past 6 h of data and the Random Forest algorithm. With the Raspberry Pi, the computational effort increases to 56.49 s assuming the previously mentioned parameters, but this can be improved to 34.89 s if Support Vector Machines are applied, achieving in this case an RMSE of 19.90 mg/dL. Thus, this paper concludes that local on-the-fly forecasting of glycaemia would be affordable with constrained devices., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Machine learning techniques combined with wearable electronics can deliver accurate short-term blood glucose level prediction models. These models can learn personalized glucose-insulin dynamics based on the sensor data collected by monitoring several aspects of the physiological condition and daily activity of an individual. Until now, the prevalent approach for developing data-driven prediction models was to collect as much data as possible to help physicians and patients optimally adjust therapy. The objective of this work was to investigate the minimum data variety, volume, and velocity required to create accurate person-centric short-term prediction models. We developed a series of these models using different machine learning time series forecasting techniques suitable for execution within a wearable processor. We conducted an extensive passive patient monitoring study in real-world conditions to build an appropriate data set. The study involved a subset of type 1 diabetic subjects wearing a flash glucose monitoring system. We comparatively and quantitatively evaluated the performance of the developed data-driven prediction models and the corresponding machine learning techniques. Our results indicate that very accurate short-term prediction can be achieved by only monitoring interstitial glucose data over a very short time period and using a low sampling frequency. The models developed can predict glucose levels within a 15-min horizon with an average error as low as 15.43 mg/dL using only 24 historic values collected within a period of sex hours, and by increasing the sampling frequency to include 72 values, the average error is reduced to 10.15 mg/dL. Our prediction models are suitable for execution within a wearable device, requiring the minimum hardware requirements while at simultaneously achieving very high prediction accuracy.

Cutaneous mucormycosis due to Saksenaea vasiformis species is exceptional. There have been about 40 reported cases worldwide, with most being fatal. We report an exceptional nonlethal case of mucormycosis due to S. vasiformis following a spider bite. The patient was in an immunosuppressed state owing to previous chemotherapy and diabetes mellitus. The origin of the inoculation was the bite of a Loxosceles laeta spider, which caused loxoscelism. The initial skin injury was quickly progressive, requiring amputation of the right upper limb. After surgical intervention and suitable antifungal treatment, the patient was discharged with resolution of accompanying pulmonary disease. Infections due to S. vasiformis are probably underdiagnosed. To avoid fatal outcomes, a high index of clinical suspicion in patients with quickly progressive necrotic lesions of soft tissues and systemic dissemination is important., (Copyright © 2019 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Overnutrition due to a high-fat diet (HFD) can increase the vulnerability of the metabolic system to maladjustments. Estradiol has an inhibitory role on food intake and this hormone has demonstrated to be a crucial organizer during brain development., Objective: Our aim was to determine whether increased levels of estradiol in the early postnatal period modulate the alterations in metabolism and brain metabolic circuits produced by overnutrition., Methods: Twenty-four male and 24 female Wistar rats were submitted to a HFD (34.9% fat) or a control diet (5% fat) from gestational day 6. From postnatal (P) 6 to P13, both control and HFD groups were administered a s.c. injection of vehicle or estradiol benzoate (0.4 mg/kg), resulting in eight experimental groups (n = 6 in each group). Body weight, food intake and subcutaneous, visceral, and brown fat pads were measured. Agouti-related peptide, neuropeptide Y, orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay and plasma estradiol levels were measured by ELISA., Results: Males fed a HFD showed an increase in body weight and the amount of visceral and subcutaneous fat, which was coincident with an increase in the number of kilocalories ingested. Neonatal estradiol treatment restored the body weight and subcutaneous fat of HFD males to control levels. Hypothalamic POMC mRNA levels in HFD females were increased with respect to control females. This increase was reverted with estradiol treatment during development., Discussion: HFD and estradiol treatment have different effects on males and females. Overnutrition affects physiological parameters, such as body weight, visceral, and subcutaneous fat content, in males, while females present alterations in hypothalamic POMC mRNA levels. Hence, the increase in estradiol levels during a period that is critical for the programing of the feeding system can modulate some of the alterations produced by the continuous intake of high-fat content food.

Type 1 diabetes mellitus (DM1) is a growing disease, and a deep understanding of the patient is required to prescribe the most appropriate treatment, adjusted to the patient's habits and characteristics. Before now, knowledge regarding each patient has been incomplete, discontinuous, and partial. However, the recent development of continuous glucose monitoring (CGM) and new biomedical sensors/gadgets, based on automatic continuous monitoring, offers a new perspective on DM1 management, since these innovative devices allow the collection of 24-hour biomedical data in addition to blood glucose levels. With this, it is possible to deeply characterize a diabetic person, offering a better understanding of his or her illness evolution, and, going further, develop new strategies to manage DM1. This new and global monitoring makes it possible to extend the "on-board" concept to other features. This well-known approach to the processing of variable "insulin" describes some inertias and aggregated/remaining effects. In this work, such analysis is carried out along with a thorough study of the significant variables to be taken into account/monitored-and how to arrange them-for a deep characterization of diabetic patients. Lastly, we present a case study evaluating the experience of the continuous and comprehensive monitoring of a diabetic patient, concluding that the huge potential of this new perspective could provide an acute insight into the patient's status and extract the maximum amount of knowledge, thus improving the DM1 management system in order to be fully functional.

This paper provides a performance evaluation of tree and mesh routing topologies of wireless sensor networks (WSNs) in a cultural heritage site. The historical site selected was San Juan Bautista church in Talamanca de Jarama (Madrid, Spain). We report the preliminary analysis required to study the effects of heating in this historical location using WSNs to monitor the temperature and humidity conditions during periods of weeks. To test which routing topology was better for this kind of application, the WSNs were first deployed on the upper floor of the CAEND institute in Arganda del Rey simulating the church deployment, but in the former scenario there was no direct line of sight between the WSN elements. Two parameters were selected to evaluate the performance of the routing topologies of WSNs: the percentage of received messages and the lifetime of the wireless sensor network. To analyze in more detail which topology gave the best performance, other communication parameters were also measured. The tree topology used was the collection tree protocol and the mesh topology was the XMESH provided by MEMSIC (Andover, MA, USA). For the scenarios presented in this paper, it can be concluded that the tree topology lost fewer messages than the mesh topology., Competing Interests: The authors declare no conflict of interest.

A new family of acidity sensitive fluorescent macrocycles has been synthesized and fully characterized. Their photophysical properties including emission quantum yield and fluorescence lifetime have been determined. The acid-base properties of the new molecules can be tuned by the incorporation of pendant functional groups. The nature of such functional groups (carboxylic acid or ester) influences dramatically the pKa of the probes, two compounds of which exhibit low values. Preliminary intracellular studies using confocal microscopy together with emission spectra of the probes from the cellular environment have shown that the synthesized fluorescent macrocycles mark the acidic organelles of RAW 264.7 macrophage cells.