Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses.

OBJECTIVE: To assess the efficacy and safety of aripiprazole for psychosis associated with Alzheimer dementia (AD). METHODS: In this double-blind, multicenter study, 487 institutionalized patients with psychosis associated with AD were randomized to placebo or aripiprazole, 2, 5 or 10 mg/day. Primary efficacy assessment was the mean change from baseline to week 10 on the Neuropsychiatric Inventory-Nursing Home (NPI-NH) version Psychosis Subscale score. Secondary measures included NPI-NH Total, Clinical Global Impression-Severity of Illness (CGI-S), Brief Psychiatric Rating Scale (BPRS) Core and Total, and the Cohen-Mansfield Agitation Inventory (CMAI) scores. RESULTS: Aripiprazole 10 mg/day showed significantly greater improvements (mean change [2 x SD]) than placebo on the NPI-NH Psychosis Subscale (-6.87 [8.6] versus -5.13 [10.0]; F = 6.29, df = 1, 422, p = 0.013 by analysis of covariance [ANCOVA]); CGI-S (-0.72 [1.8] versus -0.46 [1.6]; F = 4.68, df = 1, 419, p = 0.031 [ANCOVA]); BPRS Total (-7.12 [18.4] versus -4.17 [21.6]; F = 4.72, df = 1, 399, p = 0.030 [ANCOVA]); BPRS Core (-3.07 [6.9] versus -1.74 [7.8]; F = 7.30, df = 1, 407, p = 0.007 [ANCOVA]); CMAI (-10.96 [22.6] versus -6.64 [28.6]; F = 5.23, df = 1, 410, p = 0.023 [ANCOVA]), and NPI-NH Psychosis response rate (65 versus 50%; chi(2) = 5.52, df = 1, p = 0.019 [CMH]). Aripiprazole 5 mg/day showed significant improvements versus placebo on BPRS and CMAI scores. Aripiprazole 2 mg/day was not efficacious. Cerebrovascular adverse events were reported: aripiprazole 2 mg/day, N = 1; 5 mg/day, N = 2; 10 mg/day, N = 4; placebo, N = 0. No deaths in any group (aripiprazole 2 mg/day, 3%; 5 mg/day, 2%; 10 mg/day, 7%; placebo, 3%) were considered to be treatment-related. CONCLUSION: Aripiprazole 10 mg/day was efficacious and safe for psychosis associated with AD, significantly improving psychotic symptoms, agitation, and clinical global impression. However, clinicians should be aware of the safety considerations of atypical antipsychotic uses in this population.     

Daughters caregiving for hispanic and non-hispanic alzheimer patients: Does ethnicity make a difference?

This study assessed Cuban-American Hispanic and White non-Hispanic daughters who were major caregivers for their mothers suffering from Alzheimer's Disease. Although patients in both ethnic groups did not differ in their level of cognitive and functional impairment, Cuban-American Hispanic patients were significantly more likely to be living in their daughters' homes while the White non-Hispanic patients resided in institutional settings. Caregivers were equivalent in their knowledge and utilization of community services, but Cuban-American daughters were significantly more aware of financial aid resources. Cuban-American patients were significantly more depressed than their White non-Hispanic counterparts with daughters showing similar but nonsignificant trends. The impact of cultural factors on caregiving is discussed.     

Melanin pigmentation in mammalian skin and its hormonal regulation

Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents interacting via pathways activated by receptor-dependent and -independent mechanisms, in hormonal, auto-, para-, or intracrine fashion. Because of the multidirectional nature and heterogeneous character of the melanogenesis modifying agents, its controlling factors are not organized into simple linear sequences, but they interphase instead in a multidimensional network, with extensive functional overlapping with connections arranged both in series and in parallel. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortins and ACTH, whereas among the negative regulators agouti protein stands out, determining intensity of melanogenesis and also the type of melanin synthesized. Within the context of the skin as a stress organ, melanogenic activity serves as a unique molecular sensor and transducer of noxious signals and as regulator of local homeostasis. In keeping with these multiple roles, melanogenesis is controlled by a highly structured system, active since early embryogenesis and capable of superselective functional regulation that may reach down to the cellular level represented by single melanocytes. Indeed, the significance of melanogenesis extends beyond the mere assignment of a color trait.     

In Vivo Antiplaque Effect of Three Edible Toothpastes

Objectives: The objective of this study was to analyse the antibacterial and antiplaque activity of three edible toothpastes with the widest worldwide distribution: KidScents™, which contains essential oils; Browning B&B™, with medicinal plants; and Wysong Probiodent™, which contains probiotics. Study Design: The study group was formed of twenty healthy volunteers (dental students) with a good oral health status. Using a balanced randomisation system, all volunteers performed toothbrushing with four products (the three edible toothpastes and water) at intervals of one week. Bacterial vitality in the saliva was analysed by epifluorescence microscopy and plaque regrowth was evaluated using the Turesky-Quigley-Hein plaque index. Results: Bacterial vitality in the saliva was significantly higher after toothbrushing with water (positive control) than with the three toothpastes (P=0.002, P=0.003 and P<0.001, respectively). The plaque index was significantly higher after using these three toothpastes than after toothbrushing with water (P=0.047, P=0.032 and P<0.001, respectively). Conclusions: The three edible toothpastes analysed have some antimicrobial activity but favour plaque regrowth. Key words:Edible toothpaste, dental plaque, oral bacteria.     

An accumulator model for spontaneous neural activity prior to self-initiated movement

A gradual buildup of neuronal activity known as the “readiness potential” reliably precedes voluntary self-initiated movements, in the average time locked to movement onset. This buildup is presumed to reflect the final stages of planning and preparation for movement. Here we present a different interpretation of the premovement buildup. We used a leaky stochastic accumulator to model the neural decision of “when” to move in a task where there is no specific temporal cue, but only a general imperative to produce a movement after an unspecified delay on the order of several seconds. According to our model, when the imperative to produce a movement is weak, the precise moment at which the decision threshold is crossed leading to movement is largely determined by spontaneous subthreshold fluctuations in neuronal activity. Time locking to movement onset ensures that these fluctuations appear in the average as a gradual exponential-looking increase in neuronal activity. Our model accounts for the behavioral and electroencephalography data recorded from human subjects performing the task and also makes a specific prediction that we confirmed in a second electroencephalography experiment: Fast responses to temporally unpredictable interruptions should be preceded by a slow negative-going voltage deflection beginning well before the interruption itself, even when the subject was not preparing to move at that particular moment.     

Variants in genes of innate immunity,appetite control and energy metabolism are associated with host cardiometabolic health and gut microbiota composition

ABSTRACT

Identifying the genetic and non-genetic determinants of obesity and related cardiometabolic dysfunctions is cornerstone for their prevention, treatment, and control. While genetic variants contribute to the cardiometabolic syndrome (CMS), non-genetic factors, such as the gut microbiota, also play key roles. Gut microbiota is intimately associated with CMS and its composition is heritable. However, associations between this microbial community and host genetics are understudied. We contribute filling this gap by genotyping 60 variants in 39 genes of three modules involved in CMS risk, measuring cardiometabolic risk factors, and characterizing gut microbiota in a cohort of 441 Colombians. We hypothesized that CMS risk variants were correlated with detrimental levels of clinical parameters and with the abundance of disease-associated microbes. We found several polymorphisms in genes of innate immunity, appetite control, and energy metabolism that were associated with metabolic dysregulation and microbiota composition; the associations between host genetics and cardiometabolic health were independent of the participants’ gut microbiota, and those between polymorphisms and gut microbes were independent of the CMS risk. Associations were also independent of the host genetic ancestry, diet and lifestyle. Most microbes explaining genetic-microbiota associations belonged to the families Lachnospiraceae and Ruminococcaceae. Multiple CMS risk alleles were correlated with increased abundance of beneficial microbiota, suggesting that the phenotypic outcome of the evaluated variants might depend upon the genetic background of the studied population and its environmental context. Our results provide additional evidence that the gut microbiota is under the host genetic control and present pathways of host–microbe interactions.     

Anomalies of the urinary tract associated with congenital heart diseases

Due to the frequent association of congenital heart disease and urinary tract malformations we studied 434 patients undergoing angiocardiograms for diagnosis of their congenital heart disease. In every patient a plain abdominal X-ray film was made in order to observe urinary elimination of the contrast material. We found 70 patients with urinary tract malformations, the most frequent of which was pyelo-chaliceal dilatation, accounting for 47.1% of all the malformations found. A double pyelo-chaliceal system was found in 25.7%, kidney hypoplasia in 10% and in lower frequencies double urethers, kidney agenesia, pelvic kidneys, horseshoe-shaped kidney and others. Patients were usually urologically asymptomatic. In view of the frequent association of congenital heart disease and urinary tract malformations a plain abdominal X-ray film should always be performed postangiographically. In some cases a contrast urography is recommended.