Beyond the floor effect on the WISC-IV in individuals with Down syndrome: are there cognitive strengths and weaknesses?

BACKGROUND: Individuals with Down syndrome generally show a floor effect on Wechsler Scales that is manifested by flat profiles and with many or all of the weighted scores on the subtests equal to 1. METHOD: The main aim of the present paper is to use the statistical Hessl method and the extended statistical method of Orsini, Pezzuti and Hulbert with a sample of individuals with Down syndrome (n = 128; 72 boys and 56 girls), to underline the variability of performance on Wechsler Intelligence Scale for Children-Fourth Edition subtests and indices, highlighting any strengths and weaknesses of this population that otherwise appear to be flattened. RESULTS: Based on results using traditional transformation of raw scores into weighted scores, a very high percentage of subtests with weighted score of 1 occurred in the Down syndrome sample, with a floor effect and without any statistically significant difference between four core Wechsler Intelligence Scale for Children-Fourth Edition indices. The results, using traditional transformation, confirm a deep cognitive impairment of those with Down syndrome. Conversely, using the new statistical method, it is immediately apparent that the variability of the scores, both on subtests and indices, is wider with respect to the traditional method. CONCLUSION: Children with Down syndrome show a greater ability in the Verbal Comprehension Index than in the Working Memory Index.

Neuropsychiatric aid in children born to patients with rheumatic diseases.

A chronic disease may have an adverse impact on patients' quality of life and on their relationship styles. If this occurs in a mother, the related emotional and physical distress can interfere with baby holding, impacting on the antenatal maternal-foetal attachment and on the upbringing and development of the baby. Ineffective holding leads to the persistence of a condition of 'vulnerability to stress' and the possible development of psychosomatic problems in the offspring. In this paper we present our experience and a review from the current literature on the psychological aspects of pregnancy and parenthood in women with rheumatic diseases (RD) and children's development. To ameliorate family global quality of life, different experts (the rheumatologist, the obstetric, the neonatologist, the psychologist and the neuropsychiatric experts) should cooperate in teamwork to keep the patients' needs integrated. In particular, the neuropsychiatric intervention might support the patients and their partners throughout the experience of pregnancy and parenthood and prevent the occurrence of psychopathologic traits.

Altered Kv2.1 functioning promotes increased excitability in hippocampal neurons of an Alzheimer's disease mouse model.

Altered neuronal excitability is emerging as an important feature in Alzheimer's disease (AD). Kv2.1 potassium channels are important modulators of neuronal excitability and synaptic activity. We investigated Kv2.1 currents and its relation to the intrinsic synaptic activity of hippocampal neurons from 3xTg-AD (triple transgenic mouse model of Alzheimer's disease) mice, a widely employed preclinical AD model. Synaptic activity was also investigated by analyzing spontaneous [Ca(2+)]i spikes. Compared with wild-type (Non-Tg (non-transgenic mouse model)) cultures, 3xTg-AD neurons showed enhanced spike frequency and decreased intensity. Compared with Non-Tg cultures, 3xTg-AD hippocampal neurons revealed reduced Kv2.1-dependent Ik current densities as well as normalized conductances. 3xTg-AD cultures also exhibited an overall decrease in the number of functional Kv2.1 channels. Immunofluorescence assay revealed an increase in Kv2.1 channel oligomerization, a condition associated with blockade of channel function. In Non-Tg neurons, pharmacological blockade of Kv2.1 channels reproduced the altered pattern found in the 3xTg-AD cultures. Moreover, compared with untreated sister cultures, pharmacological inhibition of Kv2.1 in 3xTg-AD neurons did not produce any significant modification in Ik current densities. Reactive oxygen species (ROS) promote Kv2.1 oligomerization, thereby acting as negative modulator of the channel activity. Glutamate receptor activation produced higher ROS levels in hippocampal 3xTg-AD cultures compared with Non-Tg neurons. Antioxidant treatment with N-Acetyl-Cysteine was found to rescue Kv2.1-dependent currents and decreased spontaneous hyperexcitability in 3xTg-AD neurons. Analogous results regarding spontaneous synaptic activity were observed in neuronal cultures treated with the antioxidant 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Our study indicates that AD-related mutations may promote enhanced ROS generation, oxidative-dependent oligomerization, and loss of function of Kv2.1 channels. These processes can be part on the increased neuronal excitability of these neurons. These steps may set a deleterious vicious circle that eventually helps to promote excitotoxic damage found in the AD brain.

Response of general practitioners to a national dental office evaluation program. Office of Quality Assurance.

The methods used and the results achieved in an effort to solicit 300 volunteers to test the feasibility of a dental office assessment instrument have been described. In response to personal letters to general practitioners in 14 states, 13.9% returned a card indicating a willingness to consider participation. The response rate from different states ranged from 8% to 21.7% with the response being more favorable from states with fewer dentists. Year of graduation from dental school had little effect on the rate of response. Rural dentists responded at a slightly more favorable rate. Of dentists responding, 71% did so within 2 weeks and 90% within the first month after receiving the solicitation. Mail solicitation can be used successfully in recruiting private practitioners for participation in an in-office practice assessment program.

Decreased whole-blood global DNA methylation is related to serum hormones in anorexia nervosa adolescents.

OBJECTIVES: The one-carbon metabolism, also known as methionine-homocysteine cycle, governs the dynamics of DNA methylation, epigenetically regulating gene expression, and has been reported altered in anorexia nervosa (AN) adult patients. The aim of this study consisted in assessing whole-blood DNA methylation in adolescent AN patients, assessing its significance in relationship to clinical and hormonal variables. METHODS: Whole-blood global DNA methylation was measured as incorporation of [(3)H]dCTP following HpaII cut in 32 adolescent females affected by restrictive type AN and compared to 13 healthy controls. Homocysteine, vitamin B12 and folate plasma levels were assessed as well as fasting plasma levels of leptin and steroid hormones. Clinical variables, including severity and associate states and traits, were assessed by means of the EDI-3, CDI and STAI-Y scales. RESULTS: We confirm that whole-blood global DNA methylation is modestly albeit significantly reduced in AN adolescents with respect to controls, correlating with plasma leptin and steroid hormone levels. Conversely, clinical traits did not correlate with the outcome variable. CONCLUSIONS: A better definition of the epigenetic dysregulation underlying AN pathology or vulnerability might lead to develop useful markers for diagnosis, prognostic classification and tailored therapeutic interventions in these vulnerable patients since the earliest phases of their disease.

Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals.

Recent studies have shown that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia. Insulin resistance is often associated with T2DM and can induce defective insulin signaling in the central nervous system as well as increase the risk of cognitive impairment in the elderly. Glucagone like peptide-1 (GLP-1) is an incretin hormone and, like GLP-1 analogs, stimulates insulin secretion and has been employed in the treatment of T2DM. GLP-1 and GLP-1 analogs also enhance synaptic plasticity and counteract cognitive deficits in mouse models of neuronal dysfunction and/or degeneration. In this study, we investigated the potential neuroprotective effects of long-term treatment with exenatide, a GLP-1 analog, in two animal models of neuronal dysfunction: the PS1-KI and 3xTg-AD mice. We found that exenatide promoted beneficial effects on short- and long-term memory performances in PS1-KI but not in 3xTg-AD animals. In PS1-KI mice, the drug increased brain lactate dehydrogenase activity leading to a net increase in lactate levels, while no effects were observed on mitochondrial respiration. On the contrary, exenatide had no effects on brain metabolism of 3xTg-AD mice. In summary, our data indicate that exenatide improves cognition in PS1-KI mice, an effect likely driven by increasing the brain anaerobic glycolysis rate.

Effects of long-term treatment with pioglitazone on cognition and glucose metabolism of PS1-KI, 3xTg-AD, and wild-type mice.

In this study, we investigated the effects of long-term (9-month) treatment with pioglitazone (PIO; 20 mg/kg/d) in two animal models of Alzheimer's disease (AD)-related neural dysfunction and pathology: the PS1-KI(M146V) (human presenilin-1 (M146V) knock-in mouse) and 3xTg-AD (triple transgenic mouse carrying AD-linked mutations) mice. We also investigated the effects on wild-type (WT) mice. Mice were monitored for body mass changes, fasting glycemia, glucose tolerance, and studied for changes in brain mitochondrial enzyme activity (complexes I and IV) as well as energy metabolism (lactate dehydrogenase (LDH)). Cognitive effects were investigated with the Morris water maze (MWM) test and the object recognition task (ORT). Behavioral analysis revealed that PIO treatment promoted positive cognitive effects in PS1-KI female mice. These effects were associated with normalization of peripheral gluco-regulatory abnormalities that were found in untreated PS1-KI females. PIO-treated PS1-KI females also showed no statistically significant alterations in brain mitochondrial enzyme activity but significantly increased reverse LDH activity.PIO treatment produced no effects on cognition, glucose metabolism, or mitochondrial functioning in 3xTg-AD mice. Finally, PIO treatment promoted enhanced short-term memory performance in WT male mice, a group that did not show deregulation of glucose metabolism but that showed decreased activity of complex I in hippocampal and cortical mitochondria. Overall, these results indicate metabolically driven cognitive-enhancing effects of PIO that are differentially gender-related among specific genotypes.

Alterations of brain and cerebellar proteomes linked to Aß and tau pathology in a female triple-transgenic murine model of Alzheimer's disease.

The triple-transgenic Alzheimer (3 × Tg-AD) mouse expresses mutant PS1(M146V), APP(swe), and tau(P301L) transgenes and progressively develops plaques and neurofibrillary tangles with a temporal- and region-specific profile that resembles the neuropathological progression of Alzheimer's disease (AD). In this study, we used proteomic approaches such as two-dimensional gel electrophoresis and mass spectrometry to investigate the alterations in protein expression occurring in the brain and cerebellum of 3 × Tg-AD and presenilin-1 (PS1) knock-in mice (animals that do not develop Aß- or tau-dependent pathology nor cognitive decline and were used as control). Finally, using the Ingenuity Pathway Analysis we evaluated novel networks and molecular pathways involved in this AD model. We identified several differentially expressed spots and analysis of 3 × Tg-AD brains showed a significant downregulation of synaptic proteins that are involved in neurotransmitter synthesis, storage and release, as well as a set of proteins that are associated with cytoskeleton assembly and energy metabolism. Interestingly, in the cerebellum, a structure not affected by AD, we found an upregulation of proteins involved in carbohydrate metabolism and protein catabolism. Our findings help to unravel the pathogenic brain mechanisms set in motion by mutant amyloid precursor protein (APP) and hyperphosphorylated tau. These data also reveal cerebellar pathways that may be important to counteract the pathogenic actions of Aß and tau, and ultimately offer novel targets for therapeutic intervention.

Neuropsychological development of children born to patients with antiphospholipid syndrome.

OBJECTIVE: To verify the occurrence of learning disabilities (LDs) in the offspring of women with primary antiphospholipid syndrome (APS) as a consequence of fetal exposure to maternal antiphospholipid antibodies (aPL), and to evaluate the impact of maternal chronic disease on children's development. METHODS: We studied 17 children of mothers with primary APS using a standardized intelligence test (Wechsler Intelligence Scale for Children, Revised), a specific LD battery of tests (Sartori, MT groups' test for reading ability, MT groups' test for math skills), and a questionnaire on behavioral and social characteristics (Child Behavior Checklist [CBCL]). Mothers were interviewed about their pregnancy and motherhood experience. RESULTS: All children had a normal intelligence level (full-scale intelligence quotient >85); 15 pregnancies occurred in mothers with IgG aPL. LDs were diagnosed in 4 children (26.7%), 2 boys and 2 girls. One of these children was born premature, with a brother also affected. Four children (26.7%) showed a higher risk to present problems on the CBCL total competence scale and 2 children (13.3%) on the CBCL total behavior scale. Two children were described as hyperactive (1 had an LD). All families had a good socioeconomic status and educational level. CONCLUSION: Besides prematurity and genetic and environmental factors, the genesis of LDs may also include in utero exposure to aPL, in agreement with described experimental models and patients with systemic lupus erythematosus. Socioeconomic status does not seem to influence the occurrence of LDs. A long-term multidisciplinary followup may improve quality of life in patients with primary APS and their children.

EPR study of serum ceruloplasmin and iron transferrin in myocardial infarction.

Electron paramagnetic resonance (EPR) analysis of frozen serum from myocardial infarction patients has been conducted. Signal at g=4.3 was found definitively attributable to iron(III)-transferrin complex. Imcrease of serum ceruloplasmin as compared to normal was confirmed, with a concomitant decrease of iron-transferrin content. A mechanism for such correlated variation is hypothesized.

Elevated rates of schizophrenia in a familial sample with mental illness and intellectual disability.

BACKGROUND: It is unknown whether intellectual disability (ID) is more familially related to psychotic mood disorders or schizophrenia. L. S. Penrose's large sample of families with two or more members admitted to psychiatric hospitals provided a unique opportunity to investigate the familial relationship between mild ID, schizophrenia and psychotic affective disorders. METHOD: There were 183 affected relative pairs comprising probands with mild ID (95 male, 88 female) and their first or second degree relatives with schizophrenia or psychotic affective disorder. RESULTS: There were nearly twice as many relatives with a diagnosis of schizophrenia (n = 121) as relatives with affective disorders (n = 62) among the intellectually impaired probands. This excess of schizophrenia was statistically significant, even after accounting for the increased risk of hospitalization for schizophrenia (P = 0.005), and was fairly constant across the different relative types. First-degree relatives with either mental illness were more likely to be parents (n = 77) than siblings (n = 51) or children (n = 3), but there was no excess of mother-son pairs. CONCLUSIONS: These results suggest a stronger familial relationship of ID with schizophrenia than psychotic affective disorder, and lend some support to the neurodevelopmental hypothesis of schizophrenia.

[Echocardiographic study of the Björk-Shiley disc prosthesis (author's transl)]. / Studio ecocardiografico delle protesi a disco di Björk-Shiley

The echocardiography of 25 patients with Björk-Shiley disc prosthesis (16 aortic, 7 mitralic, 1 both mitralic and aortic and 1 both mitralic and tricuspidal) was studied. Mitralic prosthesis were placed with the shortest disc segment looking forward; aortic prosthesis faced the shortest disk segment looking towards the coronaric sinus. The echo's morphology is related to the multiple relationships among position and direction of the prosthesis and the probe. In the aortic echocardiogram, it is possible to recognize echoes from the ring dissociated by anterior and posterior aortic walls. Between them echoes corresponding to the open disc appear, making a quadrangular figure. The values of the internal diameter of the ring obtained were very similar to the real value (difference 0-1 mm). Mitralic echocardiogram is characterized by the valvular disc movement tracing the typical quadrangular pattern, which is due to its opening and closure. Echoes of the supporting apparatus can be recorded directing the probe toward the heart base. In aortic and mitralic prosthesis, disc movements can be estimated. Opening and closure speed rate and their correlation vary on a large scale, both within different patients and in the same patient. Maximum disc excursion appears to be a more homogeneous and constant data in long-term controls and can be used to estimate valvular functionality: in aortic prosthesis valve the obtained value (mean = 17.46 +/- 0.53 "ES") is similar to the real diameter of the disc, in mitral prosthesis valve the value obtained (mean = 17.50 +/- 0.74 "ES") is shorter than the real value.