Evaluation of refrigerated platelet concentrates supplemented with low doses of second messenger effectors

With the goal of producing haemostatically effective platelet concentrates (PCs) with a longer shelf-life, we aimed to identify a simple combination of platelet inhibitors, with a low pharmacological load, which could avoid the unacceptable loss of platelets stored under refrigerated conditions. PCs stored with different combinations of second messenger effectors were analysed at days 5, 10 and 15 of storage and compared with those supplemented with ThromboSol--a combination of six platelet inhibitors that protects cells from cold damage. The following parameters were analysed: platelet counts, biochemical parameters (glucose, pH, bicarbonate, lactate), cell lysis (lactic dehydrogenase, LDH), membrane glycoproteins (GPs), platelet aggregation, fibrinogen binding and hypotonic shock response. We characterized the combination of amiloride and sodium nitroprusside (at 1/2 the dose included in ThromboSol). This was found to be similar to ThromboSol and superior to nontreated units in the prevention of cold-induced platelet aggregation at day 15 of storage (maintenance of 78% and 80% of initial platelet counts, respectively), preservation of GPIbalpha (11% and 12% better maintenance of mean fluorescence intensity compared with control units, respectively), and reduced cell lysis (13% and 11% decrease in supernatant LDH, respectively). The reduced pharmacological load with the identified solution compared with ThromboSol is an argument in favour of the potential use of these agents when designing strategies to improve PC storage.     

A 6q14.1‐q15 microdeletion in a male patient with severe autistic disorder,lack of oral language,and dysmorphic features with concomitant presence of a maternally inherited Xp22.31 copy number gain

We report on a male patient with severe autistic disorder, lack of oral language, and dysmorphic features who carries a rare interstitial microdeletion of 4.96 Mb at chromosome 6q14.1‐q15. The patient also harbors a maternally inherited copy number gain of 1.69 Mb at chromosome Xp22.31, whose pathogenicity is under debate.     

Monte Carlo method for the evaluation of symptom association

Gastroesophageal monitoring is limited to 96 hours by the current technology. This work presents a computational model to investigate symptom association in gastroesophageal reflux disease with larger data samples proving important deficiencies of the current methodology that must be taking into account in clinical evaluation. A computational model based on Monte Carlo analysis was implemented to simulate patients with known statistical characteristics Thus, sets of 2000 10‐day‐long recordings were simulated and analyzed using the symptom index (SI), the symptom sensitivity index (SSI), and the symptom association probability (SAP). Afterwards, linear regression was applied to define the dependency of these indexes with the number of reflux, the number of symptoms, the duration of the monitoring, and the probability of association. All the indexes were biased estimators of symptom association and therefore they do not consider the effect of chance: when symptom and reflux were completely uncorrelated, the values of the indexes under study were greater than zero. On the other hand, longer recording reduced variability in the estimation of the SI and the SSI while increasing the value of the SAP. Furthermore, if the number of symptoms remains below one‐tenth of the number of reflux episodes, it is not possible to achieve a positive value of the SSI. A limitation of this computational model is that it does not consider feeding and sleeping periods, differences between reflux episodes or causation. However, the conclusions are not affected by these limitations. These facts represent important limitations in symptom association analysis, and therefore, invasive treatments must not be considered based on the value of these indexes only until a new methodology provides a more reliable assessment.     

Differential effects of single versus repeated alcohol withdrawal on the expression of endocannabinoid system-related genes in the rat amygdala

Background: Endogenous cannabinoids such as anandamide and 2‐arachidonoylglycerol (2‐AG) exert important regulatory influences on neuronal signaling, participate in short‐ and long‐term forms of neuroplasticity, and modulate stress responses and affective behavior in part through the modulation of neurotransmission in the amygdala. Alcohol consumption alters brain endocannabinoid levels, and alcohol dependence is associated with dysregulated amygdalar function, stress responsivity, and affective control. Methods: The consequence of long‐term alcohol consumption on the expression of genes related to endocannabinoid signaling was investigated using quantitative RT‐PCR analyses of amygdala tissue. Two groups of ethanol (EtOH)‐exposed rats were generated by maintenance on an EtOH liquid diet (10%): the first group received continuous access to EtOH for 15 days, whereas the second group was given intermittent access to the EtOH diet (5 d/wk for 3 weeks). Control subjects were maintained on an isocaloric EtOH‐free liquid diet. To provide an initial profile of acute withdrawal, amygdala tissue was harvested following either 6 or 24 hours of EtOH withdrawal. Results: Acute EtOH withdrawal was associated with significant changes in mRNA expression for various components of the endogenous cannabinoid system in the amygdala. Specifically, reductions in mRNA expression for the primary clearance routes for anandamide and 2‐AG (fatty acid amide hydrolase [FAAH] and monoacylglycerol lipase [MAGL], respectively) were evident, as were reductions in mRNA expression for CB₁, CB₂, and GPR55 receptors. Although similar alterations in FAAH mRNA were evident following either continuous or intermittent EtOH exposure, alterations in MAGL and cannabinoid receptor‐related mRNA (e.g., CB₁, CB₂, GPR55) were more pronounced following intermittent exposure. In general, greater withdrawal‐associated deficits in mRNA expression were evident following 24 versus 6 hours of withdrawal. No significant changes in mRNA expression for enzymes involved in 2‐AG biosynthesis (e.g., diacylglicerol lipase‐α/β) were found in any condition. Conclusions: These findings suggest that EtOH dependence and withdrawal are associated with dysregulated endocannabinoid signaling in the amygdala. These alterations may contribute to withdrawal‐related dysregulation of amygdalar neurotransmission.     

Age and distraction are determinants of performance on a novel visual search task in aged Beagle dogs

Aging has been shown to disrupt performance on tasks that require intact visual search and discrimination abilities in human studies. The goal of the present study was to determine if canines show age-related decline in their ability to perform a novel simultaneous visual search task. Three groups of canines were included: a young group (N = 10; 3 to 4.5 years), an old group (N = 10; 8 to 9.5 years), and a senior group (N = 8; 11 to 15.3 years). Subjects were first tested for their ability to learn a simple two-choice discrimination task, followed by the visual search task. Attentional demands in the task were manipulated by varying the number of distracter items; dogs received an equal number of trials with either zero, one, two, or three distracters. Performance on the two-choice discrimination task varied with age, with senior canines making significantly more errors than the young. Performance accuracy on the visual search task also varied with age; senior animals were significantly impaired compared to both the young and old, and old canines were intermediate in performance between young and senior. Accuracy decreased significantly with added distracters in all age groups. These results suggest that aging impairs the ability of canines to discriminate between task-relevant and -irrelevant stimuli. This is likely to be derived from impairments in cognitive domains such as visual memory and learning and selective attention.     

Effects of physical activity on cardiovascular disease

Much attention has been directed toward lifestyle modifications as effective means of reducing cardiovascular disease risk. In particular, physical activity has been heavily studied because of its well-known effects on metabolic syndrome, insulin sensitivity, cardiovascular disease risk, and all-cause mortality. However, data regarding the effects of exercise on various stages of the atherosclerosis pathway remain conflicting. The investigators review previously published reports for recent observational and interventional trials investigating the effects of physical activity on markers of (or causal factors for) atherosclerotic burden and vascular disease, including serum lipoproteins, systemic inflammation, thrombosis, coronary artery calcium, and carotid intima-media thickness. In conclusion, the data show a correlation between physical activity and triglyceride reduction, apolipoprotein B reduction, high-density lipoprotein increase, change in low-density lipoprotein particle size, increase in tissue plasminogen activator activity, and decrease in coronary artery calcium. Further research is needed to elucidate the effect of physical activity on inflammatory markers and intima-media thickness.     

Growth and development considerations for craniomaxillofacial surgery

The purpose of craniomaxillofacial surgery is to improve function, occlusion, craniofacial balance, and aesthetics. Accurate diagnosis, assessment, and careful treatment planning are essential in achieving a successful outcome, and an understanding of the pattern of facial growth is integral in this process. Patients with craniofacial congenital dysmorphologies, posttraumatic asymmetries, or disturbances of facial balance from radiation may have functional and/or aesthetic issues that require treatment. Understanding the complexities of growth in the skull and face is a key component to appropriate treatment planning for these disorders. This article reviews growth and development in the craniofacial skeleton.