[Predictive model and discriminant analysis of the development of dementia in patients with delirium in the emergency department]. / Modelo predictivo y análisis discriminante del desarrollo de demencia en pacientes con delirium en urgencias.

OBJECTIVE: The main aim of our study is to know the sociodemographic, clinical, analytical, and functional variables that predict the probability of developing dementia in patients with delirium who attend the emergency room. METHOD: All patients with delirium (n=45) from the emergency room who were admitted to the Geriatrics service of the General University Hospital of Ciudad Real (HGUCR) in 2016-2018 and met the inclusion and exclusion criteria were included. Subsequently, we ran a bivariate and multivariate analysis of the variables that predicted a diagnosis of dementia at six months and a discriminant analysis. RESULTS: 15.6% of patients presented dementia at six months of follow-up, 22.2% had developed cognitive impairment. We conducted a multivariate model (R2 Nagelkerke 0.459) for the probability of developing dementia, with elevated heart rate being the most crucial variable (OR=11.5). The model could excluded dementia with 100% accuracy. Finally, we achieved a discriminant function capable of correctly classifying 95.6% of the cases. It included the following variables of influence: pH, Lawton Brody index, calcium, urea, and heart rate. CONCLUSIONS: A few clinical and analytical variables that are easily detectable in the emergency room, especially tachycardia, could help us better identify those patients with delirium at higher risk of developing dementia, as well as formulate hypotheses about the variables involved in the development of dementia in patients with delirium.

[Cadmium polyneuropathy: a rare, but not less important, cause of peripheral neuropathy]. / Polineuropatía por cadmio: una causa infrecuente, pero no menos importante, de neuropatía periférica.

INTRODUCTION: Cadmium is an important heavy metal in neurobiology, with potential neurotoxic effects, often in the form of polyneuropathy (PNP). CASE REPORT: We present an exceptional case of PNP due to cadmium of toxic-occupational origin, specifically a 47-year-old man, aeronautical mechanic, with a 5-year clinical picture, consisting of a tingling sensation having a 'glove and stocking' distribution of symptoms and bimanual manipulative clumsiness. The neurological examination revealed bilateral achilles hyporeflexia and protopathic-thermal-algesic exteroceptive hypoesthesia in hands and feet. The following complementary rests were requested: toxic-metabolic-infectious-vitamin profile, full craniospinal MRI, electroneurographic-electromyographic study (ENG-EMG) of the upper and lower limbs, PET-CT body and 24-hour video-electroencephalogram. The results were consistent with an axonal, distal, symmetric sensory-motor PNP, of moderate intensity, chronic evolution, with active denervation, of toxic-occupational origin due to cadmium. The patient continued on sick leave to cease exposure to cadmium, initiating intensive multimodal neurorehabilitation program, with serial analytical determinations of toxins and new ENG-EMG studies every 6 months. With normalization of the altered values ??and complete clinical restitution at one-year follow-up. CONCLUSIONS: This case highlights the importance of including the toxicological determination of cadmium in case of suspicion of a PNP of toxic-occupational origin, once ruled out other etiologies, in order to early interrupt occupational exposure, as it is a potentially reversible cause of peripheral neuropathy. Currently there is no specific pharmacological treatment against cadmium tested in humans. Randomized clinical trials carried out in these patients are warranted to develop an anti-cadmium drug in refractory cases despite the end of exposure.

TITLE: Polineuropatía por cadmio: una causa infrecuente, pero no menos importante, de neuropatía periférica.Introducción. El cadmio es un metal pesado importante en neurobiología, con potenciales efectos neurotóxicos, frecuentemente en forma de polineuropatía. Caso clínico. Presentamos un caso excepcional de polineuropatía por cadmio de origen tóxico-ocupacional, en concreto, un varón de 47 años, mecánico aeronáutico, con un cuadro de cinco años de evolución, consistente en sensación de hormigueo 'en guante y calcetín' y torpeza manipulativa bimanual. En la exploración destacaba una hiporreflexia aquílea bilateral, y una hipoestesia exteroceptiva protopático-térmico-algésica en las manos y los pies. Se solicitó analítica general completa con perfil tóxico-metabólico-infeccioso-vitamínico, resonancia magnética craneomedular completa, estudio electroneurográfico-electromiográfico de los miembros superiores e inferiores, tomografía por emisión de positrones-tomografía axial computarizada body y videoelectroencefalograma de 24 horas. Los resultados fueron compatibles con una polineuropatía sensitivomotora axonal, distal, simétrica, de intensidad moderada, de evolución crónica y desnervación activa, de origen tóxico-ocupacional por cadmio. El paciente prosiguió la baja laboral para cesar la exposición al cadmio, iniciando neurorrehabilitación intensiva multimodal, y determinaciones analíticas seriadas de tóxicos y nuevos estudios electroneurográficos-electromiográficos cada seis meses, con normalización de los valores alterados y restitución clínica ad integrum al año. Conclusiones. Este caso enfatiza la importancia de incluir la determinación toxicológica del cadmio ante la sospecha de una polineuropatía de origen tóxico-ocupacional, descartadas otras etiologías, para interrumpir precozmente dicha exposición laboral, al ser una causa potencialmente reversible de neuropatía periférica. Actualmente no existe un tratamiento farmacológico específico frente al cadmio demostrado en seres humanos. Urgen ensayos clínicos aleatorizados en estos pacientes, para desarrollar un fármaco frente al cadmio en casos refractarios pese a finalizar la exposición.

Cerebrospinal and blood levels of amino acids as potential biomarkers for Parkinson's disease: review and meta-analysis.

BACKGROUND AND PURPOSE: The present systematic review and meta-analysis aims to establish the possible value of cerebrospinal fluid (CSF) and serum/plasma levels of amino acids as markers of Parkinson's disease (PD). METHODS: This is a review of four databases (PubMed, Embase, MEDLINE and Web of Science - Core Collection) from 1966 to 14 March 2020, with identification of references of interest for the topic. The meta-analysis of eligible studies was done using R software package meta, following the PRISMA and MOOSE guidelines. RESULTS: Compared with age- and sex-matched controls, PD patients showed decreased CSF levels of glutamate and taurine and increased CSF levels of tyrosine; decreased serum/plasma levels of aspartate, serine, tryptophan and lysine, and increased serum/plasma proline and homocysteine levels. CONCLUSION: Despite the limitations of this study due to the important variability of results between different series, our findings suggest the value of CSF or serum/plasma levels of several amino acids in the discrimination of PD patients from healthy subjects, related to the levels of some amino acids.

Periprosthetic infection in elderly patients treated with hemiarthroplasty of the hip following intracapsular fracture. Should we use antibiotic-loaded bone cement? / Infección periprótesica en pacientes ancianos tratados mediante hemiartroplastia de cadera tras fractura intracapsular. ¿Debemos usar cementación con antibiótico?

INTRODUCTION: Prosthetic infections are a potentially devastating complication, especially in elderly patients. Antibiotic-loaded bone cement has been used both as a treatment and prophylaxis in prosthetic infection, and its use is not well documented in the prophylaxis of infection in patients who have suffered a hip fracture. MATERIAL: A retrospective descriptive was performed. The data were obtained from all the patients who underwent hip hemiarthroplasty due to a subcapital fracture between 2011 and 2017 (N=241). An epidemiological study of the patients studied was carried out. We analysed the incidence of periprosthetic infection in the groups treated with cement without antibiotic and antibiotic-loaded bone cement, as well as the protective effect of the antibiotic-loaded bone cement. At the same time, a pilot cost analysis study was carried out. RESULTS: In the group that received antibiotic-loaded bone cement (n=94) there were 8 infections (8%), while in the group with cement without antibiotic (n=147) there were 28 infections (19%). The odds ratio (OR) was calculated, showing a 55.3% reduction in the risk of developing late infection in the group that received cement with antibiotic (95% CI: 6.2-78.7%, P=.0025). The use of antibiotic-loaded bone cement led to significant cost savings per patient. CONCLUSIONS: The use of antibiotic-loaded bone cement is a protective factor in the development of late infection after hip hemiarthroplasty surgery in elderly patients with hip fracture.

Short Review: Investigating ARSACS: models for understanding cerebellar degeneration.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease that includes progressive cerebellar dysfunction. ARSACS is caused by an autosomal recessive loss-of-function mutation in the SACS gene, which encodes for SACSIN. Although animal models are still necessary to investigate the role of SACSIN in the pathology of this disease, more reliable human cellular models need to be generated to better understand the cerebellar pathophysiology of ARSACS. The discovery of human induced pluripotent stem cells (hiPSC) has permitted the derivation of patient-specific cells. These cells have an unlimited self-renewing capacity and the ability to differentiate into different neural cell types, allowing studies of disease mechanism, drug discovery and cell replacement therapies. In this study, we discuss how the hiPSC-derived cerebellar organoid culture offers novel strategies for targeting the pathogenic mutations related to ARSACS. We also highlight the advantages and challenges of this 3D cellular model, as well as the questions that still remain unanswered.

[Drug-related mortality among inpatients admitted in Internal Medicine]. / Mortalidad hospitalaria asociada a medicamentos en un Servicio de Medicina Interna.

BACKGROUND: To analyze the mortality associated with prescriptions, the drugs most frequently involved and the associated risk factors in patients admitted to Internal Medicine. METHODS: A retrospective, observational study. The clinical records of adult patients who died consecutively in the department of Internal Medicine in a Spanish tertiary hospital over twenty-two months were reviewed. The main variable was the prevalence of hospital death suspected of being related to the medications administered during admission. RESULTS: Out of the 455 deaths analyzed, 22.2% were related to the medications received; in 55 cases (12.1%) the drugs were suspected of being the cause of death and in 46 cases (10.1%) of contributing to it. The most frequent diagnoses in cases of death associated with drugs were cardiac arrhythmia (23.7%), severe hemorrhage (19.8%) and aspiration pneumonia (12.8%). The drugs with the highest prevalence in deaths related to pharmacological treatment were an-tithrombotic drugs (23.7%), digoxin (21.7%), antipsychotics (17.8%) and benzodiazepines (14.8%). The only independent risk factor for mortality associated with treatment was the number of medications administered (OR=1.25, 95%CI: 1.14-1.37). No significant association was found with age, sex, number of pathologies or duration of hospital stay. CONCLUSION: A high percentage of deaths of patients admitted to Internal Medicine were considered related to the medications received. Antithrombotic drugs, digoxin and psychotropic drugs were the agents most frequently implicated. This mortality is independently and significantly associated with the number of medications administered.

[Hereditary primary microcephaly type 5. Not everything is Zika virus]. / Microcefalia primaria hereditaria de tipo 5. No todo es virus del Zika.

TITLE: Microcefalia primaria hereditaria de tipo 5. No todo es virus del Zika.

[Intraarticular lesions associated with tibial fixation during anterior cruciate ligament reconstruction]. / Lesiones intraarticulares asociadas a la fijación tibial en la reconstrucción del ligamento cruzado anterior.

Anterior cruciate ligament reconstruction is a demanding procedure; complications may arise at any of its stages. This is the report of three cases in which the tibial fixation devices (IntraFix and Bio-IntraFix) led to intraarticular lesions. The complications were detected in one of the cases while the patient was still in the operating room and in the remaining two during the follow-up. All the patients had a stable knee, but all of them sustained chondral lesions resulting from the inadequate placement of the implants used for tibial fixation. Several suggestions to avoid the complications stemming from these devices are provided.

La reconstrucción del ligamento cruzado anterior es un procedimiento exigente; las complicaciones pueden presentarse en cualquiera de sus etapas. Presentamos tres casos en los cuales los dispositivos para la fijación tibial (IntraFix y Bio-IntraFix) condicionaron lesiones intraarticulares. Las complicaciones fueron detectadas, en uno de los casos, mientras el paciente se encontraba aún en la sala de operaciones, y en los otros dos, durante el seguimiento. Todos los pacientes contaban con una rodilla estable, pero tuvieron lesiones condrales causadas por la inadecuada colocación de los implantes para la fijación tibial. Se exponen algunas sugerencias para evitar complicaciones con estos dispositivos.

Piezoelectric energy harvesting computer controlled test bench.

In this paper a new computer controlled (C.C.) laboratory test bench is presented. The patented test bench is made up of a C.C. road traffic simulator, C.C. electronic hardware involved in automating measurements, and test bench control software interface programmed in LabVIEW™. Our research is focused on characterizing electronic energy harvesting piezoelectric-based elements in road traffic environments to extract (or "harvest") maximum power. In mechanical to electrical energy conversion, mechanical impacts or vibrational behavior are commonly used, and several major problems need to be solved to perform optimal harvesting systems including, but no limited to, primary energy source modeling, energy conversion, and energy storage. It is described a novel C.C. test bench that obtains, in an accurate and automatized process, a generalized linear equivalent electrical model of piezoelectric elements and piezoelectric based energy store harvesting circuits in order to scale energy generation with multiple devices integrated in different topologies.

Exposure to bisphenol A and behavior in school-age children.

INTRODUCTION: Bisphenol A (BPA) exposure has been shown to affect human brain neurodevelopment and behavior. OBJECTIVE: We aimed to investigate whether environmental exposure to BPA in children was associated with their childhood behavior. METHODS: Urinary BPA concentrations and behavioral characteristics were assessed in 300 children belonging to the INMA "Environment and Childhood" Granada birth cohort in their follow-up at 9-11 years of age. BPA concentrations were quantified in urine using liquid chromatography-tandem mass spectrometry (LC-MS-MS), and child behavior reported by parents using the Child Behavior Checklist (CBCL/6-18) under supervision of a psychologist. The association between BPA concentrations and CBCL standardized scores was analyzed using linear regression models, adjusted for important covariates. RESULTS: Median (P25, P75) BPA concentration was 4.76 (2.77, 9.03)µg/L. Mean (±SD) CBCL externalizing and internalizing scores were 56.35 (±8.06) and 51.36 (±9.22), respectively. In multivariate regression analyses, adjusted for maternal and child characteristics, higher BPA concentrations were associated with worse behavioral scores on all scales. Children with BPA concentrations in the 4th quartile had more somatic complaints (ß=2.35; 95% CI: 0.25, 4.46) and social (ß=1.71; 95% CI: 0.19, 3.22) and thought problems (ß=2.58; 95% CI: 0.66, 4.51) in comparison to those in the 1st quartile. Children with values in the 3rd quartile of BPA concentrations also showed greater social problems (ß=1.94; 95% CI: 0.43, 3.45). CONCLUSIONS: Our results suggest that exposure to BPA in childhood may affect children's behavior. Although further investigations are required, preventive measures should be undertaken to reduce inadvertent exposure to BPA.

Evaluation of Nutritional Biochemical Parameters in Haemodialysis Patients over a Ten-year Period.

AIM: Protein-energy malnutrition as well as systemic inflammation and metabolic disorders are common in patients with chronic kidney failure, who require renal replacement therapy (haemodialysis). Such malnutrition is a factor that significantly contributes to their morbidity and mortality. This study evaluated the nutritional status of haemodialysis patients by assessing biochemical and anthropometric parameters in order to determine whether these patients suffered disorders reflecting nutritional deterioration directly related to time on haemodialysis. SUBJECTS AND METHOD: This research comprised 90 patients of both genders with chronic kidney failure, who regularly received haemodialysis at our unit over a period of ten years. The patients' blood was tested quarterly for plasma albumin, total cholesterol and total proteins, and tested monthly for transferrin. The patients' weight, height and body mass index (BMI) were monitored. Body mass index was calculated using the formula: weight (kg)/height (m2 ) and classified in one of the following categories defined in the World Health Organization (WHO) Global Database on Body Mass Index: (i) underweight [BMI < 18.50], (ii) normal [BMI 18.50 - 24.99], (iii) overweight [BMI 25 - 29.99], (iv) obese [BMI > 30]. RESULTS: In the ten-year period of the study, the patients experienced a substantial decline in their biochemical parameters. Nevertheless, their BMI did not show any significant changes despite the patients' state of malnutrition. CONCLUSIONS: The prevalence of malnutrition in haemodialysis patients was evident. Nevertheless, the BMI of the subjects did not correspond to the biochemical parameters measured. Consequently, the results showed that the nutritional deterioration of these patients was mainly reflected in their biochemical parameters rather than in their anthropometric measurements.

Efficacy of an extravascular lung water-driven negative fluid balance protocol.

OBJECTIVE: To analyze the efficacy of negative fluid balance in hypoxemic patients with an elevated extravascular lung water index (EVLWI). DESIGN: A retrospective observational study was made. SETTING: Intensive Care Unit of Virgen de las Nieves Hospital (Spain). PARTICIPANTS: Forty-four patients participated in the study. INTERVENTIONS: We analyzed our database of hypoxemic patients covering a period of 11 consecutive months. We included all hemodynamically stable and hypoxemic patients with EVLWI>9ml/kg. The protocol dictates a negative fluid balance between 500 and 1500ml/day. We analyzed the impact of this negative fluid balance strategy upon pulmonary, hemodynamic, and renal function. MAIN VARIABLES OF INTEREST: Demographic data, severity scores, clinical, hemodynamic, pulmonary, metabolic and renal function data. RESULTS: Thirty-three patients achieved negative fluid balance (NFB group) and 11 had a positive fluid balance (PFB group). In the former group, PaO2/FiO2 improved from 145 (IQR 106, 200) to 210mmHg (IQR 164, 248) (p<0.001), and EVLWI decreased from 14 (11, 18) to 10ml/kg (8, 14) (p<0.001). In the PFB group, EVLWI also decreased from 11 (10, 14) to 10ml/kg (8, 14) at the end of the protocol (p=0.004). For these patients there were no changes in oxygenation, with a PaO2/FiO2 of 216mmHg (IQR 137, 260) at the beginning versus 205mmHg (IQR 99,257) at the end of the study (p=0.08). CONCLUSION: Three out of four hypoxic patients with elevated EVLWI tolerated the NFB protocol. In these subjects, the improvement of various analyzed physiological parameters was greater and faster than in those unable to complete the protocol. Patients who did not tolerate the protocol were usually in more severe condition, though a larger sample would be needed to detect specific characteristics of this group.

A novel human glycoprotein ACA is an upstream regulator of human hematopoiesis.

A central issue in stem cell biology is a better understanding of the molecular mechanisms that regulate self-renewal of human hematopoietic stem cells (HSCs). Control of the specific function of HSCs like self-renewal and differentiation might be regulated by a common set of critical genes. However, the regulation among these genes is yet to be elucidated. Here, we show that activation by a novel human GPI-linked glycoprotein ACA at the surface of human peripheral blood progenitor cells induces via PI3K/Akt/mTor/PTEN upregulation of WNT, Notch1, Bmi-1 and HoxB4 genes thus, promoting self-renewal and generation of primitive HSCs. ACA-generated self-renewing cells retained their lympho-myeloid repopulating potential in NOD/SCID mouse xeno-transplantation model with long term functional capacity. We conclude that ACA is an essential regulator of the genes involved in maintaining hematopoiesis and its use in clinical praxis could overcome many of the barriers present so far in transplantation medicine.

Activation by ACA induces pluripotency in human blood progenitor cells.

Reprogramming of human somatic cells by transcription factors to pluripotent state holds great promise for regenerative medicine. However, low efficiencies of current reprogramming methods, immunogenicity and lack of understanding regarding the molecular mechanisms responsible for their generation, limits their utilization and raises questions regarding safety for therapeutic application. Here we report that ACA signaling via PI3K/Akt/mTor induces sustained de-differentiation of human blood progenitor cells leading to generation of ACA pluripotent stem cells. Blood-derived pluripotent stem cells differentiate in vitro into cell types of all three germ layers, exhibiting neuronal, liver, or endothelial characteristics. Our results reveal insight into the molecular events regulating cellular reprogramming and also indicate that pluripotency might be controlled in vivo through binding of a natural ligand(s) to ACA receptor enabling reprogramming through defined pathway(s) and providing a safe and efficient method for generation of pluripotent stem cells which could be a breakthrough in human therapeutics.