Validation of a Spanish Version of the Lille Apathy Rating Scale for Parkinson’s Disease

Introduction. To date, no rating scales for detecting apathy in Parkinson’s disease (PD) patients have been validated in Spanish. For this reason, the aim of this study was to validate a Spanish version of Lille apathy rating scale (LARS) in a cohort of PD patients from Spain. Participants and Methods. 130 PD patients and 70 healthy controls were recruited to participate in the study. Apathy was measured using the Spanish version of LARS and the neuropsychiatric inventory (NPI). Reliability (internal consistency, test-retest, and interrater reliability) and validity (construct, content, and criterion validity) were measured. Results. Interrater reliability was 0.93. Cronbach’s α for LARS was 0.81. The test-retest correlation coefficient was 0.97. The correlation between LARS and NPI scores was 0.61. The optimal cutoff point under the ROC curve was , whereas the value derived from healthy controls was . The prevalence of apathy in our population tested by LARS was 42%. Conclusions. The Spanish version of LARS is a reliable and useful tool for diagnosing apathy in PD patients. Total LARS score is influenced by the presence of depression and cognitive impairment. However, both disorders are independent identities with respect to apathy. The satisfactory reliability and validity of the scale make it an appropriate instrument for screening and diagnosing apathy in clinical practice or for research purposes.

Amaurose e alterações neuropsiquiátricas como apresentação de neurossífilis

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

A doença de Parkinson no doente idoso

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Anxiety and depression symptoms in liver encephalopathy : are they psychiatric or organic?

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Efavirenz versus Nevirapina : comparação da efectividade e do perfil de segurança, a longo prazo, no tratamento da infecção por vírus da imunodeficiência humana tipo 1

Tese de mestrado, Doenças Infecciosas Emergentes, Universidade de Lisboa, Faculdade de Medicina, 2016

Maternal separation followed by isolation-housing differentially affects prepulse inhibition of the acoustic startle response in C57BL/6 mice

Exposure to chronic stress is associated with an increased incidence of neuropsychiatric dysfunction. The current study evaluated two competing hypotheses, the cumulative stress and the match/mismatch hypothesis of neuropsychiatric dysfunction, using two paradigms relating to exposure to “stress”: pre-weaning maternal separation and post-weaning isolation-housing. C57BL/6 offspring were reared under four conditions: typical animal facility rearing (AFR, control), early handling (EH, daily 15 min separation from dam), maternal separation (MS, daily 4 hr separation from dam), and maternal and peer separation (MPS, daily 4 hr separation from dam and from littermates). After weaning, mice were either housed socially (2–3/cage) or in isolation (1/cage) and then tested for prepulse inhibition in adulthood. Isolation-housed MPS subjects displayed greater deficits in prepulse inhibition relative to socially-housed MPS subjects while socially-housed AFR subjects displayed greater deficits in prepulse inhibition relative to isolation-housed AFR subjects. The results indicate that these treatment conditions represent a potentially valuable model for evaluating the match/mismatch hypothesis in regards to neuropsychiatric dysfunction.

Minor intron splicing is regulated by FUS and affected by ALS-associated FUS mutants

Fused in sarcoma (FUS) is a ubiquitously expressed RNA-binding protein proposed to function in various RNA metabolic pathways, including transcription regulation, pre-mRNA splicing, RNA transport and microRNA processing. Mutations in the FUS gene were identified in patients with amyotrophic lateral sclerosis (ALS), but the pathomechanisms by which these mutations cause ALS are not known. Here, we show that FUS interacts with the minor spliceosome constituent U11 snRNP, binds preferentially to minor introns and directly regulates their removal. Furthermore, a FUS knockout in neuroblastoma cells strongly disturbs the splicing of minor intron-containing mRNAs, among them mRNAs required for action potential transmission and for functional spinal motor units. Moreover, an ALS-associated FUS mutant that forms cytoplasmic aggregates inhibits splicing of minor introns by trapping U11 and U12 snRNAs in these aggregates. Collectively, our findings suggest a possible pathomechanism for ALS in which mutated FUS inhibits correct splicing of minor introns in mRNAs encoding proteins required for motor neuron survival.

Behavioural and histopathological alterations in mice with cerebral malaria.

Different features of sensorimotor function and behaviour were studied in murine cerebral malaria (CM) and malaria without cerebral involvement (non-CM) applying the primary screen of the SHIRPA protocol. Histopathological analysis of distinct brain regions was performed and the relative size of haemorrhages and plugging of blood cells to brain vasculature was analysed. Animals suffering from CM develop a wide range of behavioural and functional alterations in the progressive course of the disease with a statistically significant impairment in all functional categories assessed 36 h prior to death when compared with control animals. Early functional indicators of cerebral phenotype are impairments in reflex and sensory system and in neuropsychiatric state. Deterioration in function is paralleled by the degree of histopathological changes with a statistically significant correlation between the SHIRPA score of CM animals and the mean size of brain haemorrhage. Furthermore, image analysis yielded that the relative area of the brain lesions was significantly larger in the forebrain and brainstem compared with the other regions of interest. Our results indicate that assessment of sensory and motor tasks by the SHIRPA primary screen is appropriate for the early in vivo discrimination of cerebral involvement in experimental murine malaria. Our findings also suggest a correlation between the degree of functional impairment and the size of the brain lesions as indicated by parenchymal haemorrhage. Applying the SHIRPA protocol in the functional characterization of animals suffering from CM might prove useful in the preclinical assessment of new antimalarial and potential neuroprotective therapies.

Sleep loss and its effects on performance /

Includes indexes.

Mefloquine and doxycycline malaria prophylaxis in Australian soldiers in East Timor

Objectives: To describe the tolerability of mefloquine in Australian soldiers for malaria prophylaxis, including a comparison with doxycycline. Design: Open-label, prospective study and cross-sectional questionnaire and interview. Setting and participants: Two contingents of Australian soldiers, each deployed to East Timor for peacekeeping duties over a 6-month period (April 2001-October 2001 and October 2001-May 2002). Outcome measures: Withdrawals during the study; adverse events relating to mefloquine prophylaxis; willingness to use mefloquine again on deployment. Results: Of 1157 soldiers starting on mefloquine, 75 (6.5%) withdrew because of adverse responses to the drug. There were three serious adverse events of a neuropsychiatric nature, possibly relating to mefloquine. Fifty-seven per cent of soldiers using mefloquine prophylaxis reported at least one adverse event, compared with 56% using doxycycline. The most commonly reported adverse effects of both drugs were sleep disturbance, headache, tiredness and nausea. Of the 968 soldiers still taking mefloquine at the end of their deployments, 94% indicated they would use mefloquine again. Of 388 soldiers taking doxycycline prophylaxis who were deployed with the first mefloquine study contingent, 89% indicated they would use doxycycline again. Conclusions: Mefloquine was generally well tolerated by Australian soldiers and should continue to be used for those intolerant of doxycycline.

Prevalence and patterns of anxiety and depression in patients undergoing elective percutaneous transluminal coronary angioplasty

Background The use of elective percutaneous transluminal coronary angioplasty (PTCA) as a treatment for coronary heart disease is increasing. Despite this, little is known about the prevalence and patterns of anxiety and depression experienced by patients undergoing and recovering from this procedure. Anxiety and depression are factors known to negatively influence recovery after a cardiac event. Objective The purpose of this study was to (1) describe the levels of anxiety and depression reported by patients pre- and postelective PTCA, and (2) determine associations evident between anxiety and depression and the sociodemographic and clinical variables of gender, marital status, history of acute myocardial infarction, and attendance at cardiac rehabilitation. Methods In this descriptive, repeated-measures investigation, patients (n = 140) were requested to complete the Spielberger State Trait Anxiety Inventory and Cardiac Depression Scale (CDS) at three time points: 0(1) before admission for elective PTCA (T1); (2) 6 to 8 weeks (T2) after PTCA; and (3) 6 to 8 months (T3) after PTCA. Results A typical participant was male (75%), of European ethnicity (90%), aged 62 years (standard deviation = 10.7) with single or double vessel disease, and had attended cardiac rehabilitation in the past. At T1, 16% of men and 24% of women had state anxiety scores comparable to those experienced by neuropsychiatric patients. Trait anxiety scores remained relatively constant over time; higher scores at T1 were associated with past acute myocardial infarction. CDS scores at T2 and T3 were significantly lower than those at T1. However, an unexpected increase in CDS scores occurred at T3, compared with T2. At T3, 14% of men and 10% of women were depressed, relative to T1. Conclusion The findings lend support for the closer surveillance of emotional status in this population. Specialist nurses have the potential to play a greater role in identifying those at risk of developing anxiety and depression. However, this unmet need will remain unmet until specialist nurses who spend the most face-to-face time with patients are equipped with the skills and resources to systematically identify those “at risk.”

Symptom prevalence and clustering of symptoms in people living with chronic hepatitis C infection

Quality of life has been shown to be poor among people living with chronic hepatitis C However, it is not clear how this relates to the presence of symptoms and their severity. The aim of this study was to describe the typology of a broad array of symptoms that were attributed to hepatitis C virus (HCV) infection. Phase I used qualitative methods to identify symptoms. In Phase 2, 188 treatment-naive people living with HCV participated in a quantitative survey. The most prevalent symptom was physical tiredness (86%) followed by irritability (75%), depression (70%), mental tiredness (70%), and abdominal pain (68%). Temporal clustering of symptoms was reported in 62% of participants. Principal components analysis identified four symptom clusters: neuropsychiatric (mental tiredness, poor concentration, forgetfulness, depression, irritability, physical tiredness, and sleep problems); gastrointestinal (day sweats, nausea, food intolerance, night sweats, abdominal pain, poor appetite, and diarrhea); algesic (joint pain, muscle pain, and general body pain); and dysesthetic (noise sensitivity, light sensitivity, skin. problems, and headaches). These data demonstrate that symptoms are prevalent in treatment-naive people with HCV and support the hypothesis that symptom clustering occurs.

Spatial coherence does not affect contrast discrimination for multiple Gabor stimuli

Gestalt grouping rules imply a process or mechanism for grouping together local features of an object into a perceptual whole. Several psychophysical experiments have been interpreted as evidence for constrained interactions between nearby spatial filter elements and this has led to the hypothesis that element linking might be mediated by these interactions. A common tacit assumption is that these interactions result in response modulation which disturbs a local contrast code. We addressed this possibility by performing contrast discrimination experiments using two-dimensional arrays of multiple Gabor patches arranged either (i) vertically, (ii) in circles (coherent conditions), or (iii) randomly (incoherent condition), as well as for a single Gabor patch. In each condition, contrast increments were applied to either the entire test stimulus (experiment 1) or a single patch whose position was cued (experiment 2). In experiment 3, the texture stimuli were reduced to a single contour by displaying only the central vertical strip. Performance was better for the multiple-patch conditions than for the single-patch condition, but whether the multiple-patch stimulus was coherent or not had no systematic effect on the results in any of the experiments. We conclude that constrained local interactions do not interfere with a local contrast code for our suprathreshold stimuli, suggesting that, in general, this is not the way in which element linking is achieved. The possibility that interactions are involved in enhancing the detectability of contour elements at threshold remains unchallenged by our experiments.

AIDS: neurological and ophthalmological aspects

Although overt ocular symptoms are not often encountered in AIDS patients, many exhibit subtile neuro-ophthalmic signs and symptoms. This article describes the neuropsychiatric symptoms as well as the neuro-ophthalmic conditions which have been reported recently in AIDS patients. The degree to which optometrists may be vulnerable to the AIDS virus from contact with patients in practice will also be discussed.

Efficacy of memantine on behavioral and psychological symptoms related to dementia:a systematic meta-analysis

BACKGROUND: The behavioral and psychological symptoms related to dementia (BPSD) are difficult to manage and are associated with adverse patient outcomes. OBJECTIVE: To systematically analyze the data on memantine in the treatment of BPSD. METHODS: We searched MEDLINE, EMBASE, Pharm-line, the Cochrane Centre Collaboration, www.clinicaltrials.gov, www.controlled-trials.com, and PsycINFO (1966-July 2007). We contacted manufacturers and scrutinized the reference sections of articles identified in our search for further references, including conference proceedings. Two researchers (IM and CF) independently reviewed all studies identified by the search strategy. We included 6 randomized, parallel-group, double-blind studies that rated BPSD with the Neuropsychiatric Inventory (NPI) in our meta-analysis. Patients had probable Alzheimer's disease and received treatment with memantine for at least one month. Overall efficacy of memantine on the NPI was established with a t-test for the average difference between means across studies, using a random effects model. RESULTS: Five of the 6 studies identified had NPI outcome data. In these 5 studies, 868 patients were treated with memantine and 882 patients were treated with placebo. Patients on memantine improved by 1.99 on the NPI scale (95% Cl -0.08 to -3.91; p = 0.041) compared with the placebo group. CONCLUSIONS: Initial data appear to indicate that memantine decreases NPI scores and may have a role in managing BPSD. However, there are a number of limitations with the current data; the effect size was relatively small, and whether memantine produces significant clinical benefit is not clear.