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Neuropsychiatric symptoms are common features of Huntington's disease (HD). Whereas most studies have focused on cognitive and neuroimaging... more
Neuropsychiatric symptoms are common features of Huntington's disease (HD). Whereas most studies have focused on cognitive and neuroimaging markers of disease progression, little is known about the prevalence of neuropsychiatric symptoms in premanifest mutation carriers far-from and close-to disease onset. We obtained neurological, cognitive and behavioral data from 230 participants classified as premanifest far-from (preHD-A) and close-to (preHD-B) motor-based disease onset, early-symptomatic (early-HD), and healthy controls. Frequency and severity of neuropsychiatric symptoms were assessed with the short Problem Behaviors Assessment for HD (PBA-s). The odds-ratio (OR) to present symptoms in the clinical range was calculated using the control group as reference. Logistic regression analysis was used to explore relationships between neuropsychiatric symptoms and medication use. Prevalence of depression was similar in all groups. Apathy was already present in 32% of preHD-A increasing to 62% of early-HD patients. The probability of presenting apathetic symptoms was 15-88 times higher in preHD-A and preHD-B respectively than in healthy controls. Irritability and executive dysfunction were present in both preHD-B and early-HD. Neuropsychiatric symptoms are highly prevalent in HD, already in the premanifest stage, with increasing prevalence of irritability, apathy and executive dysfunction closer to onset. Compared to controls, HD mutation carriers have the highest probability to develop apathy, with an increasing prevalence along disease stages. Our findings confirm the high prevalence of neuropsychiatric symptoms in HD, already many years before the onset of motor symptoms, with apathy as an early manifestation and core neuropsychiatric feature of the disease.
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Introduction Neuropsychiatric features are characteristic symptoms in Huntington’s disease (HD). Compelling evidence proved high prevalence of alterations on mood and affect. However, little is known about psychotic symptoms in HD.... more
Introduction Neuropsychiatric features are characteristic symptoms in Huntington’s disease (HD). Compelling evidence proved high prevalence of alterations on mood and affect. However, little is known about psychotic symptoms in HD. Objective Describe the characteristics and phenomenology of psychotic symptoms in a Spanish cohort of Huntington’s disease patients. Methods From the Spanish Registry cohort, genetically positive patients with psychiatric, cognitive and motor assessment were included. We analysed demographic, genetic and clinical data. Cognitive and motor functions were measured with Unified Huntington Disease Rating Scale (UHDRS), psychiatric disturbances with the Problem Behaviour Assessment Scale (PBA-s) and function with the total functional capacity (TFC). Results 264 patients were included (46.2% males; mean age of 45.2 ± 12.5y; disease duration 5.5 ± 5.5y and mean CAG 44.1 ± 4.7). Delusions were present in the 10.2% of the patients and hallucinations in 4.5%. Visual hallucinations were the more frequent 3.4% followed by auditory 1.9%. UHDRS cognitive score (p = 0.05) and TFC (p = 0.01) were more impaired in patients with psychotic symptoms. No other differences or correlations between delusions/hallucinations and cognitive, motor or functional scores were found. Formal diagnosis of schizoaffective disorder was present in two patients, previous acute psychotic episode in one, dementia in one and young HD in one. Conclusions Psychotic symptoms are infrequent in HD. Delusions are more frequent than hallucinations being the visual ones the more recurrent. Despite not found correlation, patients presenting psychosis/hallucinations are significantly more impaired on cognition and functional capacity.
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Background Parkinsonism is a common and invalidating feature of Huntington’s disease (HD) that results difficult to manage since levodopa and/or dopaminergic agonists may exacerbate chorea and psychiatric symptoms. Methods Two patients... more
Background Parkinsonism is a common and invalidating feature of Huntington’s disease (HD) that results difficult to manage since levodopa and/or dopaminergic agonists may exacerbate chorea and psychiatric symptoms. Methods Two patients exhibiting a rigid-akinetic form of HD, -with apathetic symptoms and slight depression in patient A and major depression in patient B were treated with Rasagiline (a monoaminoxidasa-B inhibitor used in Parkinson’s disease) 1mg/day. Motor function, cognition and affect were explored through the Unified Huntington Disease Rating Scale (UHDRS), neuropsychological assessment, the Hospital Anxiety and Depression Scale and the Starkstein’s Apathy Scale. Results One month after initiation of Rasagiline, motor function improved on rigidity/bradykinesia (measured with finger taps, pronate supinate-hands, bradykiensia-body and rigidity items). Patient A improved nine points (Initial UHDRS = 33, final 24) and patient B ten (Initial UHDRS = 24, final 14). No worsening on chorea neither in other items was seen. Significant amelioration of apathy and depression was also evidenced in both cases. In Patient A, apathy score decreased from 18 to 12 points and from 12 to 7 for depression. In patient B, apathy decreased from 22 to 13, while depression from 14 to 6. The Global impression of change was rated by the patients up to 70% of improvement in both cases. Neurologist rated up to 50% for patient A and 70% for patient B. Both remained stable after 3-month follow-up. Conclusions In our reported cases of HD, rasagiline appeared effective to treat parkinsonism. Future studies are needed to clarify the potential usefulness of Rasagiline for the management of HD.
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Background A frail patient is an immobilised person and/or a nursing home resident and/or in a terminal stage. This population is hyper-frequent in primary health care (PHC) centres and hospitals. This group generates large expenses in... more
Background A frail patient is an immobilised person and/or a nursing home resident and/or in a terminal stage. This population is hyper-frequent in primary health care (PHC) centres and hospitals. This group generates large expenses in drugs and they usually need a nasogastric tube (NGT). Purpose To evaluate the implementation of pharmacy assistance for frail patients with NGT after hospital discharge. Material and methods Prospective study conducted between June and September 2014. Sequence of activities: a physician or nurse selected the patients who require pharmaceutical intervention to guarantee the correct administration of drugs via NGT, compatibility with enteral nutrition and stability of solid solutions or dispersions of drugs. A report with recommendations, substitutions and interruptions of treatments was issued to the patient. Variables: age, drugs per patient, therapeutic group (TG) according to the Anatomical Therapeutic Chemical (ATC) classification system and active substances with submitted recommendations and levels of approval. Sources of information: electronic medical history (DIRAYA), electronic prescription program (APD – ATHOS) and specialised bibliography. Data was analysed using SPSS 15.0. Results 23 requests were received. The mean age of the patients was 81.65 (± 8.97) years. The mean of prescribed drugs per patient was 8 (2–19). 75% (138/184) of the patients required specific recommendations (a mean of 6 drugs per patient). The most common TGs were related to the nervous system 29.71% (41) and the cardiovascular system 25.36% (35). The most frequent active principles were: omeprazole 9.42% (13) and acetylsalicylic acid 5.8% (8). 100% of the recommendations were accepted. Conclusion This system guarantees a constant information flow between PHC centres and hospitals that will avoid problems and guarantee correct drug administration. Future studies will show the economic impact and the improvement in the quality of life with the reduction of visits to PHC centres and hospitals. References and/or Acknowledgements None. No conflict of interest.
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Protease inhibitors, mainly Indinavir, are widely used drugs for the treatment of patients infected by the human immunodeficiency virus (HIV) and are related to renal colic and urinary obstruction. These conditions are the result of urine... more
Protease inhibitors, mainly Indinavir, are widely used drugs for the treatment of patients infected by the human immunodeficiency virus (HIV) and are related to renal colic and urinary obstruction. These conditions are the result of urine excretion of these drugs which favours the formation of small calculi (crystalluria and lithiasis). Five PI treated HIV(+) patients; four males, one female, have recently been seen for renal colic at the Lithiasis Unit, Fundación Jiménez Díaz (FJD). All five patients had renal colic, one bilateral and one renal obstruction and fever. Small lithiasic concretions of null or minor radiological calcium density were identified by urinary X-ray and UIV. The patients had haematuria, crystalluria and urinary pH 5.0-6.0. Treatment was symptomatic, pharmacologic, emergency in situ extracorporeal shock-wave lithotrity (ESWL), or ureteral catheterisation, as appropriate. Patients had been treated with these antiviral agents for several months. They all require...
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Introduction Huntington’s disease (HD) is a neurodegenerative disorder that induces striatal and cortical neuronal dysfunction and loss which main symptom is motor impairment. Goals to study whether this motor impairment is accompanied by... more
Introduction Huntington’s disease (HD) is a neurodegenerative disorder that induces striatal and cortical neuronal dysfunction and loss which main symptom is motor impairment. Goals to study whether this motor impairment is accompanied by changes in brain activity and functional connectivity. Methods Fifteen early stage HD patients with a UHDRS motor score > 5 (9 men, mean age = 48 ± 8.9, mean TFC = 11.7 ± 1.17) and 15 controls (9 men, mean age = 46.6 ± 8.1) matched in age, gender and educational background underwent 3T structural and functional MRI scanning while they performed a sequential tapping task with their right or left hand in alternated blocks. Results Compared to rest blocks, active tapping activated the contralateral primary motor, premotor and supplementary motor areas, thalamus and cerebellum in both patients and controls. However, in the right hand condition, patients deactivated the right putamen to a greater extent than controls, which suggests that patients need a greater inhibition of the ipsilateral putamen in order to suppress the movement of the opposite hand. Furthermore, HD patients showed less activation in the right putamen during the left hand condition compared to controls. These effects could be ascribed to the general imbalance in the Go and No-Go cortico-striatal pathways that is believed to occur in HD. The left precentral gyrus, was selected as a seed region for a whole brain functional connectivity analysis. Compared with controls, right precentral gyrus, right SMA and right putamen were more connected (negatively) to the left precentral gyrus in patients. This indicates that not only the right putamen, but all the right motor circuit undergoes a greater deactivation in HD patients when they move their left hand. In addition, the negative functional connectivity between the left precentral gyrus and the right putamen showed a positive correlation with the motor-UHDRS score and the TFC score. Conclusions These results indicate that HD patients need to inhibit the contralateral motor circuit of the moving hand to compensate for the hyperactivation of the dopaminergic system that underlies their motor symptoms. This effect is specific to the right hemisphere, showing an asymmetry of the motor circuit dysfunction.
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... Memories Embedded in SoCst WJ Perez H.1, J. Velasco Medina', D. Ravotto2, E. Sanchez2, M. Sonza Reorda2 1 Universidad del Valle ... effective test programs. strategy is generally more affordable than hardware-based... more
... Memories Embedded in SoCst WJ Perez H.1, J. Velasco Medina', D. Ravotto2, E. Sanchez2, M. Sonza Reorda2 1 Universidad del Valle ... effective test programs. strategy is generally more affordable than hardware-based approaches, as it exploits the processor ISA instructions ...
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The morphological descriptors involve the management of attributes to carry out breeding of forage species. The objectives of the present study were to explore the morphological diversity of native populations of sideoat grama (Bouteloua... more
The morphological descriptors involve the management of attributes to carry out breeding of forage species. The objectives of the present study were to explore the morphological diversity of native populations of sideoat grama (Bouteloua curtipendula (Michx.) Torr.) and to evaluate its principal morphological characteristics. To this effect, 177 ecotypes were qualified and analyzed at the moment of flowering by means
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Research Interests: Horticulture, Soil, Water, Irrigation, Biomass, and 13 morePlant Biology, Biology, Minerals, Ecology, Agriculture, Medicine, Tree Physiology, Fruit, Tree, Plant Roots, Citrus, Forestry Sciences, and Rootstock
Analyses of Arabidopsis thaliana defense response to the damping-off oomycete pathogen Pythium irregulare show that resistance to P. irregulare requires a multicomponent defense strategy. Penetration represents a first layer, as indicated... more
Analyses of Arabidopsis thaliana defense response to the damping-off oomycete pathogen Pythium irregulare show that resistance to P. irregulare requires a multicomponent defense strategy. Penetration represents a first layer, as indicated by the susceptibility of pen2 mutants, followed by recognition, likely mediated by ERECTA receptor-like kinases. Subsequent signaling of inducible defenses is predominantly mediated by jasmonic acid (JA), with insensitive coi1 mutants showing extreme susceptibility. In contrast with the generally accepted roles of ethylene and salicylic acid cooperating with or antagonizing, respectively, JA in the activation of defenses against necrotrophs, both are required to prevent disease progression, although much less so than JA. Meta-analysis of transcriptome profiles confirmed the predominant role of JA in activation of P. irregulare–induced defenses and uncovered abscisic acid (ABA) as an important regulator of defense gene expression. Analysis of cis-re...
Research Interests: Genetics, Plant Biology, Biology, Innate immunity, Medicine, and 15 moreArabidopsis thaliana, Phylogeny, Plant diseases, Arabidopsis, Oomycetes, Callose, Abscisic Acid, Meta Analysis, Disease Progression, Plant cell, Gene Expression Analysis, Induced Defense, Biochemistry and cell biology, Jasmonic Acid, and Oxylipins
The conformational properties of the molecular chaperone GroEL in the presence of ATP, its non‐hydrolyzable analog 5′‐adenylimidodiphosphate (AMP‐PNP), and ADP have been analyzed by differential scanning calorimetry (DSC),... more
The conformational properties of the molecular chaperone GroEL in the presence of ATP, its non‐hydrolyzable analog 5′‐adenylimidodiphosphate (AMP‐PNP), and ADP have been analyzed by differential scanning calorimetry (DSC), Fourier‐transform infra‐red (FT‐IR) and fluorescence spectroscopy. Nucleotide binding to one ring promotes a decrease in the Tm value of the GroEL thermal transition that is reversed when both rings are filled with nucleotide, indicating that the sequential occupation of the two protein rings by these nucleotides has different effects on the GroEL thermal denaturation process. In addition, ATP induces a conformational change in GroEL characterized by (a) the appearance of a reversible low temperature endotherm in the DSC profiles of the protein, and (b) an enhanced binding of the hydrophobic probe 8‐anilino‐naphthalene‐1‐sulfonate (ANS), which strictly depends on ATP hydrolysis. The similar sensitivity to K+ of the temperature range where activation of the GroEL A...
Research Interests: Chemistry, Crystallography, Medicine, Differential scanning calorimetry, European, and 12 moreFourier transform infrared spectroscopy, Protein Conformation, Hydrolysis, Protein Denaturation, Conformational Change, Nucleotide, Biochemistry and cell biology, Adenosine Triphosphate, Adenosine Diphosphate, ATP hydrolysis, Medical biochemistry and metabolomics, and GroEl
Introduction The obstructive sleep apnea syndrome (OSAS) is characterized by a history of snoring and upper airway recurrent obstruction, leading to sleep fragmentation and excessive day time somnolence. Its prevalence is higher in men... more
Introduction The obstructive sleep apnea syndrome (OSAS) is characterized by a history of snoring and upper airway recurrent obstruction, leading to sleep fragmentation and excessive day time somnolence. Its prevalence is higher in men (2:1), and it has been reported that older women have a higher risk for its appearance. The main objective our work was to relate BMI, age with OSAS in obese women. Materials and methods In this study, we included 39 women with morbid obesity, with a BMI higher tan 30. All of them underwent an overnight polysomnography. We performed lineal regression and correlation tests for the statistical analysis. Results The mean age for these women was 40.6 + 1.77, the mean BMI 45.10 + 1.53 and the mean of AHI was 45.21 + 7.5. Pearson correlation IAH–BMI showed 0.727 ∗ , AHI-age 0.435 ∗ , BMI-age 0.17. IAH-BMI R 2 = 0.52 ∗ . Lineal regression AHI–BMI-age, R = 0.79 ∗ , R 2 = 0.63 ∗ , ( ∗ P ∗ , with a confidence interval CI (2.3–4.3), and age odds ratio 1.3 ∗ , CI (0.4–2.2) ∗ P Conclusion These data suggest a strong correlation between OSAS, BMI and age in women. There is a significant correlation between AHI and BMI. This relation increases when age is included. We did not find any relation between BMI and age. It is necessary to include more groups of women, with normal weight and overweight.
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A number of Arabidopsis (Arabidopsis thaliana) mutants exhibit leaf reticulation, having green veins that stand out against paler interveinal tissues, fewer cells in the interveinal mesophyll, and normal perivascular bundle sheath cells.... more
A number of Arabidopsis (Arabidopsis thaliana) mutants exhibit leaf reticulation, having green veins that stand out against paler interveinal tissues, fewer cells in the interveinal mesophyll, and normal perivascular bundle sheath cells. Here, to examine the basis of leaf reticulation, we analyzed the Arabidopsis RETICULATA-RELATED (RER) gene family, several members of which cause leaf reticulation when mutated. Although transcripts of RE, RER1, and RER3 were mainly detected in the bundle sheath cells of expanded leaves, functional RER3:GREEN FLUORESCENT PROTEIN was visualized in the chloroplast membranes of all photosynthetic cells. Leaf reticulation in the re and rer3 loss-of-function mutants occurred, along with accumulation of reactive oxygen species, in a photoperiod-dependent manner. A comparison of re and rer3 leaf messenger RNA expression profiles showed more than 200 genes were similarly misexpressed in both mutants. In addition, metabolic profiles of mature leaves revealed...
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Research Interests: Biophysics, Crystallography, Protein Folding, Biology, Transmission Electron Microscopy, and 15 moreBiological Chemistry, Medicine, Biological Sciences, Protein Structure and Function, Animals, Biological, Potassium, Asymmetry, CHEMICAL SCIENCES, Swine, Protein Conformation, Protein Binding, Adenosine Triphosphate, Medical and Health Sciences, and GroEl
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The hydroxo complexes [Ni2(mcN3)2(mu-OH)2]2(PF6)2[mcN3 = 2,4,4-trimethyl-1,5,9-triazacyclododec-1-ene (Me3-mcN3) or 2,4,4,9-tetramethyl-1,5,9-triazacyclododec-1-ene (Me4-mcN3)] react with the corresponding carboxylic acid [HA = benzoic... more
The hydroxo complexes [Ni2(mcN3)2(mu-OH)2]2(PF6)2[mcN3 = 2,4,4-trimethyl-1,5,9-triazacyclododec-1-ene (Me3-mcN3) or 2,4,4,9-tetramethyl-1,5,9-triazacyclododec-1-ene (Me4-mcN3)] react with the corresponding carboxylic acid [HA = benzoic (Hbz), salicylic (Hsal) or acetylsalicylic (Hacsal) acid] to give five-coordinate nickel(II) complexes of the type [Ni(mcN3)(A)](PF6). The complexes have been studied by spectroscopic methods (IR, UV-Vis and 1H NMR). In acetone solution they exhibit isotropically shifted 1H NMR resonances. The full assignment of these resonances has been made using one- and two-dimensional 1H NMR techniques. The single-crystal structures of [Ni(Me4-mcN3)(bz)](PF6), [Ni(Me4-mcN3)(sal)](PF6) and[Ni(Me4-mcN3)(acsal)](PF6) have been established by X-ray diffraction.
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The bis(phosphatediester)‐bridged complexes [{Ni([12]aneN3)(μ‐O2P(OR)2)}2](PF6)2 {[12]aneN3=Me3[12]aneN3, 2,4,4‐trimethyl‐1,5,9‐triazacyclododec‐1‐ene; R=Me (1), Bu (2), Ph (3), Ph‐4‐NO2 (4); [12]aneN3=Me4[12]aneN3,... more
The bis(phosphatediester)‐bridged complexes [{Ni([12]aneN3)(μ‐O2P(OR)2)}2](PF6)2 {[12]aneN3=Me3[12]aneN3, 2,4,4‐trimethyl‐1,5,9‐triazacyclododec‐1‐ene; R=Me (1), Bu (2), Ph (3), Ph‐4‐NO2 (4); [12]aneN3=Me4[12]aneN3, 2,4,4,9‐tetramethyl‐1,5,9‐triazacyclododec‐1‐ene; R=Me (5), Bu (6), Ph (7), Ph‐4‐NO2 (8)} were prepared by hydrolysis of the phosphate triester with the hydroxo complex [{Ni([12]aneN3)(μ‐OH)}2](PF6)2 or by acid–base reaction of the dialkyl or diaryl phosphoric acid and the above hydroxo complex. The acid–base reaction was also used to synthesise the phosphinate‐bridged complexes [{Ni([12]aneN3)(μ‐O2PR2)}2](PF6)2 {[12]aneN3=Me3[12]aneN3, R=Me (9), Ph (10); [12]aneN3=Me4[12]aneN3, R=Me (11), Ph (12)}. The molecular structures of complexes 2, 3 and 12 were established by single crystal X‐ray diffraction studies. The eight‐membered rings defined by the nickel atoms and the bridging ligands show distorted twist‐boat, chair and boat–boat conformations in 2, 3 and 12, respectiv...
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Background Neuropsychiatric symptoms are a common feature of Huntington’s disease (HD). Despite are identifiable years before motor-based disease onset, little is known about the prevalence and significance of neuropsychiatric symptoms in... more
Background Neuropsychiatric symptoms are a common feature of Huntington’s disease (HD). Despite are identifiable years before motor-based disease onset, little is known about the prevalence and significance of neuropsychiatric symptoms in pre-manifested (preHD) individuals. Objectives To determine the prevalence and significance of a wide range of neuropsychiatric features in positive gene carriers far and near disease onset and how they compare to early symptomatic and healthy controls. Methods Neurological, medication, cognitive and behavioural data were obtained from n = 129 gene positive and n = 101 healthy controls from the Spanish cohort of the Registry study. Participants were classified as preHD far (preHD-A; n = 34) and near (PreHD-B; n = 24) to disease onset, early-HD (n = 70) and healthy controls (n = 101). Frequency and severity of neuropsychiatric symptoms were addressed through the Problems Behaviour Assessment Scale in its short form (PBA-s). Results Clinically meaningful depressive symptoms are present in in all the groups showing no significance differences. Apathy appeared in up to 32% of preHD-A linearly increasing in frequency and severity up to 62% in Early-HD. Meaningful symptoms of irritability and executive dysfunction appeared in both preHD-B and Early-HD groups. The probability for presenting clinically meaningful apathetic symptoms appeared 15 to 88 times higher in preHD-A and preHD-B respectively compared to healthy controls. More than half of the preHD-B also presented significant symptoms of irritability and executive dysfunction. Discussion A wide range of neuropsychiatric symptoms are observable along the pre-manifested and early stage of HD. The frequency, severity and probability to develop meaningful apathetic symptoms linearly increases along disease stages. High prevalence of depressive symptoms in healthy controls should respond to the influence HD as a misrecognized environmental stressor. Longitudinal studies are needed to clarify the meaning of neuropsychiatric features in the earliest disease stages and the potential usefulness of apathy scores as early markers of disease progression.