Cerebral superb microvascular imaging in preterm neonates: in vivo evaluation of thalamic, striatal, and extrastriatal angioarchitecture.

PURPOSE: To explore the potential of superb microvascular imaging (SMI) in visualizing brain microvessels in preterm neonates of different gestational ages (GA). METHODS: In this retrospective, observational pilot study, 15 preterm newborns were equally divided into GA groups: extremely (GA < 28 weeks), very (28-31 weeks), and moderate to late (32-37 weeks) preterm. All patients underwent conventional transcranial ultrasounds during the first day of life following the American Institute of Ultrasound in Medicine practice guidelines. SMI was then performed; based on their SMI morphology and location, brain microvessels were classified as extrastriatal (cortical and medullary), striatal, or thalamic. Two examiners independently classified vessels as visible or invisible. To assess the association between vessel visibility and GA, binomial logistic regression analysis (separate for each microvessel group) was performed, taking visibility as a dependent variable and both examiners and GA as predictor variables. RESULTS: A statistically significant difference among GA groups was found in sex (P = 0.030), birth weight (P = 0.007), and Apgar score within 1 min after birth (P = 0.024). Microvascular visibility increased with GA for superficial vessels (P < 0.05 for both cortical and medullary), while striatal and thalamic vessels were visible in all neonates irrespective of their GA. CONCLUSIONS: SMI technology shows promise to assess brain microvasculature in preterm neonates, even potentially providing data on early brain development.

Preliminary risk assessment of workplace violence in hospital emergency departments.

BACKGROUND: The risk assessment of workplace violence in emergency departments represents a global challenge for both healthcare organizations and workers. Recent studies have revealed increased rates of workplace violence towards physicians and nurses employed in emergency departments and have shown that type II is the most common typology of workplace violence among the four types of workplace violence defined by the National Institute for Occupational Safety and Health. The present study aimed to develop a methodological technique for a preliminary assessment of type II workplace violence risk in emergency departments. METHODS: The Delphi method was used to develop a questionnaire entitled Emergency Department Workplace Violence-Questionnaire which was composed of two sections: 1) sentinel events, and 2) risk factors. The authors used the Emergency Department Workplace Violence-Questionnaire to evaluate the workplace violence risk among physicians and nurses employed in a hospital emergency department. RESULTS: The Emergency Department Workplace Violence-Questionnaire was composed of 21 items. The sentinel events section consisted of three company indicators related to workplace violence and identified three areas of risk. The risk factors section identified 18 organizational and environmental factors associated with workplace violence occurrence. The assessment of workplace violence risk in the targeted hospital emergency departments, obtained through the use of the Emergency Department Workplace Violence-Questionnaire, showed a medium risk of workplace violence for both physicians (score=18) and nurses (score=19.5); the analysis found objective risk factors associated with workplace violence and led us to suggest organizational and environmental interventions for reducing the sources of risk among healthcare workers and to prioritize the interventions targeted at the problematical issues detected by the Emergency Department Workplace Violence-Questionnaire. The corrective interventions were focused on an engineering level (i.e. absence of areas for patients/clients to de-escalate, absence of alarm systems) and regarding the organizational environment (i.e. absence of a Workplace Violence Task Force to assess workplace violence risk and develop solutions, working alone). CONCLUSION: The proposed questionnaire proved to be a valid, structured, and reliable tool for assessing the risk of workplace violence in the targeted emergency departments and allowed for the identification of improvement actions targeted at specific critical issues which could be minimized through strategic interventions.

Facile synthesis of 3D flower-like Pt nanostructures on polypyrrole nanowire matrix for enhanced methanol oxidation.

Here we report the simple and rapid synthesis of three-dimension Pt flower-like nanostructures (PtNFs) on a polypyrrole nanowires (PPyNWs) matrix. Both PtNFs and PPyNWs are prepared by an electrochemical approach without using any seed, template or surfactant. The morphology and chemical composition of the resulting PtNF/PPyNWs hybrids are characterized by scanning electron microscopy and by X-ray photoelectron spectroscopy, respectively. Taking methanol oxidation as a model catalysis reaction, the electrocatalytic performance of the as-prepared PtNF/PPyNWs system has been evaluated by cyclic voltammetry and chronoamperometry, evidencing that these 3D materials exhibit excellent electrocatalytic activity and high level of poisoning tolerance to the carbonaceous oxidative intermediates. Such electrocatalytic performances can be ascribed to the combined effect of the flower-like structure promoting the exposure of more sites and the polymer nanowires matrix endorsing high dispersion of PtNF on a high electrochemically active surface area, besides the removal of sub-products from electrocatalytic sites.

Polyomavirus Infection in Gouldian Finches (Erythrura gouldiae) and Other Pet Birds of the Family Estrildidae.

A syndrome characterized by apathy, diarrhoea and high mortality of nestlings was observed in a flock of pet birds of the family Estrildidae. Enlargement of the liver, pulmonary congestion and urate accretions in the kidney were observed. Microscopically, there was glomerular atrophy, oedema and congestion of the lungs and necrosis and fibrosis of the liver. Cowdry type B intranuclear inclusion bodies were detected in the tissues. Polyomavirus was detected by polymerase chain reaction. The entire genome of the virus was amplified and sequenced, revealing 99 % identity to the sequence of finch polyomavirus isolated from the Eurasian bullfinch (family Fringillidae).

Detection of the new emerging rabbit haemorrhagic disease type 2 virus (RHDV2) in Sicily from rabbit (Oryctolagus cuniculus) and Italian hare (Lepus corsicanus).

Rabbit haemorrhagic disease virus (RHDV), a member of the genus Lagovirus, causes rabbit haemorrhagic disease (RHD), a fatal hepatitis of rabbits, not previously reported in hares. Recently, a new RHDV-related virus emerged, called RHDV2. This lagovirus can cause RHD in rabbits and disease and mortality in Lepus capensis (Cape hare). Here we describe a case of RHDV2 infection in another hare species, Lepus corsicanus, during a concurrent RHD outbreak in a group of wild rabbits. The same RHDV2 strain infected rabbits and a hare, also causing a RHD-like syndrome in the latter. Our findings confirmed the capability of RHDV2 to infect hosts other than rabbits and improve the knowledge about the epidemiology and the host range of this new lagovirus.

Selection for milk coagulation properties predicted by Fourier transform infrared spectroscopy in the Italian Holstein-Friesian breed.

Milk coagulation is based on a series of physicochemical changes at the casein micelle level, resulting in formation of a gel. Milk coagulation properties (MCP) are relevant for cheese quality and yield, important factors for the dairy industry. They are also evaluated in herd bulk milk to reward or penalize producers of Protected Designation of Origin cheeses. The economic importance of improving MCP justifies the need to account for this trait in the selection process. A pilot study was carried out to determine the feasibility of including MCP in the selection schemes of the Italian Holstein. The MCP were predicted in 1,055 individual milk samples collected in 16 herds (66 ± 24 cows per herd) located in Brescia province (northeastern Italy) by means of Fourier transform infrared (FTIR) spectroscopy. The coefficient of determination of prediction models indicated moderate predictions for milk rennet coagulation time (RCT=0.65) and curd firmness (a30=0.68), and poor predictions for curd-firming time (k20=0.49), whereas the range error ratio (8.9, 6.9, and 9.5 for RCT, k20, and a30, respectively) indicated good practical utility of the predictive models for all parameters. Milk proteins were genotyped and casein haplotypes (αS1-, ß-, αS2-, and κ-casein) were reconstructed. Data from 51 half-sib families (19.9 ± 16.4 daughters per sire) were analyzed by an animal model to estimate (1) the genetic parameters of predicted RCT, k20, and a30; (2) the breeding values for these predicted clotting variables; and (3) the effect of milk protein genotypes and casein haplotypes on predicted MCP (pMCP). This is the first study to estimate both genetic parameters and breeding values of pMCP, together with the effects of milk protein genotypes and casein haplotypes, that also considered k20, probably the most important parameter for the dairy industry (because it indicates the time for the beginning of curd-cutting). Heritability of predicted RCT (0.26) and k20 (0.31) were close to the average heritability described in literature, whereas the heritability of a30 was higher (0.52 vs. 0.27). The effects of milk proteins were statistically significant and similar to those obtained on measured MCP. In particular, haplotypes including uncommon variants showed positive (B-I-A-B) or negative (B-A(1)-A-E) effects. Based on these findings, FTIR spectroscopy-pMCP is proposed as a potential selection criterion for the Italian Holstein.

Lower limb spasticity assessment using an inertial sensor: a reliability study.

Spasticity is a common motor impairment in patients with neurological disorders that can prevent functional recovery after rehabilitation. In the clinical setting, its assessment is carried out using standardized clinical scales. The aim of this study was to verify the applicability of inertial sensors for an objective measurement of quadriceps spasticity and evaluate its test-retest and inter-rater reliability during the implementation of the Wartenberg pendulum test. Ten healthy subjects and 11 patients in vegetative state with severe brain damage were enrolled in this study. Subjects were evaluated three times on three consecutive days. The test-retest reliability of measurement was assessed in the first two days. The third day was devoted to inter-rater reliability assessment. In addition, the lower limb muscle tone was bilaterally evaluated at the knee joint by the modified Ashworth scale. The factorial ANOVA analysis showed that the implemented method allowed us to discriminate between healthy and pathological conditions. The fairly low SEM and high ICC values obtained for the pendulum parameters indicated a good test-retest and inter-rater reliability of measurement. This study shows that an inertial sensor can be reliably used to characterize leg kinematics during the Wartenberg pendulum test and provide quantitative evaluation of quadriceps spasticity.

Invited review: Dairy intake and bone health: a viewpoint from the state of the art.

The aim of this review was to focus on the complex relationships between milk and dairy products intake and bone health, with particular emphasis on osteoporosis. The literature was extensively examined to provide an objective overview of the most significant achievements on the subject. Osteoporosis can be defined as a disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. Although the major determinants of peak bone mass and strength are genetic, major factors during childhood and adolescence may affect the ability to achieve peak bone mass. These include nutrition, particularly calcium and protein intake, physical activity, endocrine status, as well as exposure to a wide variety of risk factors. The role of calcium intake in determining bone mineral mass is well recognized to be the most critical nutritional factor to achieve optimal peak bone mass. The greatest amount of dietary calcium is obtained from milk and dairy foods, which also provide the human diet with vitamin D (particularly for products fortified with vitamin D), potassium, and other macro- and micronutrients. Although studies supporting the beneficial effects of milk or calcium on bone health are predominant in the literature, perplexity or discordance on this subject was expressed by some authors. Discordant data, mainly on the risk of fractures, provided limited proof of the unfavorable effect of dairy intake. More often, discordant works indicate no effect of dairy consumption on bone safety. Some considerations can be drawn from this viewpoint. Milk and dairy products are an optimal source of calcium as well as of other limiting nutrients (e.g., potassium and magnesium), with important effects on bone health. Bioactive components occurring in milk and dairy products may play an essential role on bone metabolism, as shown by in vivo and in vitro studies on colostrum acidic proteins and milk basic proteins. Calcium intake positively affects bone mass and is crucial in childhood and youth for correct bone development. In elderly people, calcium intake as well as vitamin D availability should be carefully checked. As a general conclusion, calcium is essential for bone health, although it will not prevent bone loss due to other factors; in this context, milk and dairy foods are bioavailable, relatively inexpensive sources of calcium for the human diet.

Monitoring of genetic diversity in the endangered Martina Franca donkey population.

The Martina Franca (MF) donkey, an ancient native breed of Apulia, was mostly famous for mule production. The breed was at serious risk of extinction in the 1980s following the decrease in demand for draft animals because they were increasingly replaced by agricultural machinery. Much has been done in the last few decades to safeguard the existing donkey breeds, but the situation remains critical. Successful implementation of conservation measures includes an evaluation of the present degree of breed endangerment, so the aim of this work was to analyze the demographic and genetic parameters of this breed to suggest effective conservation strategies. With a current breed register counting less than 500 recorded animals, the pedigree data set included 1,658 MF donkeys born between 1929 and 2006. Analyses were carried out on the whole data set as well as on a smaller one consisting of 422 living animals. Demographic and genetic variability parameters were evaluated using the ENDOG (v4.6) software. The pedigree completeness level was evaluated as well as the generation length, which was calculated for each of the 4 gametic pathways. This information was obtained from animal birth date records together with those of their fathers and mothers. The effective number of founders (f(e)), the effective number of ancestors (f(a)), the founder genome (f(g)), individual inbreeding (F), average relatedness (AR), and the rate of inbreeding per generation were analyzed to describe the genetic variability of the population. Because pedigree depth and completeness were appropriate, especially regarding the current population, the parameters defining genetic variability, namely, f(e), f(a), f(g), F, and AR, could be reliably estimated. Analysis of these parameters highlighted the endangerment status of the MF donkey. Our special concern was with the increased percentage of males and females exhibiting increased AR values. Moreover, the effective size of the current population, 48.08, is slightly less than the range of the minimum effective size, and the rates of inbreeding per generation found in the current MF population exceed the maximum recommended level of 1%. Such a scenario heightens concerns over the endangered status of the MF breed and calls for proper conservation measures and breeding strategies, such as selecting individuals for mating when relationships are below 12.5%.

Goat milk allergenicity as a function of αs1-casein genetic polymorphism.

Cow milk allergy is the most frequent allergy in the first years of life. Milk from other mammalian species has been suggested as a possible nutritional alternative to cow milk, but in several cases, the clinical studies showed a high risk of cross-reactivity with cow milk. In the goat species, αS1-casein (αS1-CN), coded by the CSN1S1 gene, is characterized by extensive qualitative and quantitative polymorphisms. Some alleles are associated with null (i.e., CSN1S1 0(1)) or reduced (i.e., CSN1S1 F) expression of the specific protein. The aim of this work was to obtain new information on goat milk and to evaluate its suitability for allergic subjects, depending on the genetic variation at αs1-CN. Individual milk samples from 25 goats with different CSN1S1 genotypes were analyzed by sodium dodecyl sulfate PAGE and immunoblotting, using monoclonal antibodies specific for bovine α-CN and sera from children allergic to cow milk. A lower reaction was observed to 2 goat milk samples characterized by the CSN1S1 0(1)0(1) and 0(1)F genotypes. Moreover, a fresh food skin prick test, carried out on 6 allergic children, showed the lack of positive reaction to the 0(1)0(1) milk sample and only one weak reactivity to the 0(1)F sample. The risk of cross-reactivity between cow and goat milk proteins suggests the need for caution before using goat milk for infant formulas. However, we hypothesize that it can be used successfully in the preparation of modified formulas for selected groups of allergic patients. The importance of taking the individual goat CN genetic variation into account in further experimental studies is evident from the results of the present work.

The Garfagnina goat: a zootechnical overview of a local dairy population.

Domestic livestock with a limited distribution are increasingly recognized in the action plans of the European Union as a reason for protecting rural land. The preservation and enhancement of the native germplasm and traits selected through the ages in different areas of farming is the first step in increasing typical products at a time when high quality products are increasingly in demand. This is the first time that a zootechnical overview has been performed on the Italian native goat population named "Garfagnina," which is registered on the Tuscan regional repertory of genetic resources at risk of extinction. The aim of the study was to give added value to this population by focusing on particular traits that could be used for promoting typical products. Data on the size of the local goats, zoometric measures, breeding system, milk quality, and genetic polymorphisms were collected to get insight into the current state of the population of this type of goat. The native goat population is reared in Tuscany in central Italy, mostly for its milk. The local goat farms considered in our study are located in the hills and mountains of the northwestern Tuscan Apennine area. For every farm we measured at least 10% of the reproductive females (273), randomly chosen, and all reproductive males (47) for a total of 320 subjects. Regarding the management of the animals and the feeding system, semi-extensive farming is practiced in all the flocks. From a morphological point of view the animals are relatively homogeneous, especially in terms of zoometric data, whereas they show a wider variability regarding coat. Milk gross and fatty acid composition were similar to that reported in the literature for bulk goat milk. Moreover, the average of somatic cell count and standard plate count found in Garfagnina goat milk indicated good hygienic farm management and correct milking practices, although milking is mainly manual. The average number of globules per milliliter found in Garfagnina goat milk was almost double compared with the literature, whereas the average diameter was lower. Milk coagulation properties were scarce, thus indicating poor cheesemaking aptitude of Garfagnina milk. Selecting haplotypes carrying alleles associated with a higher expression of the specific casein could help improve milk cheesemaking aptitude. Moreover, the rather high frequency of the faint CSN1S1*F allele and the occurrence of CSN2*0 might suggest that Garfagnina goat milk could be used, after an appropriate selection, for direct consumption of milk at low casein content for intolerant human subjects.

The dynamics of Alzheimer's disease biomarkers in the Alzheimer's Disease Neuroimaging Initiative cohort.

The aim of this study was to investigate the dynamics of four of the most validated biomarkers for Alzheimer's disease (AD), cerebro-spinal fluid (CSF) Abeta 1-42, tau, hippocampal volume, and FDG-PET, in patients at different stage of AD. Two hundred twenty-nine cognitively healthy subjects, 154 mild cognitive impairment (MCI) patients converted to AD, and 193 (95 early and 98 late) AD patients were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. For each biomarker, individual values were Z-transformed and plotted against ADAS-cog scores, and sigmoid and linear fits were compared. For most biomarkers the sigmoid model fitted data significantly better than the linear model. Abeta 1-42 time course followed a steep curve, stabilizing early in the disease course. CSF tau and hippocampal volume changed later showing similar monotonous trends, reflecting disease progression. Hippocampal loss trend was steeper and occurred earlier in time in APOE epsilon4 carriers than in non-carriers. FDG-PET started changing early in time and likely followed a linear decline. In conclusion, this study provides the first evidence in favor of the dynamic biomarker model which has recently been proposed.

Short communication: milk protein genetic variation and casein haplotype structure in the Original Pinzgauer cattle.

Milk protein genetic polymorphisms are often used for characterizing domesticated mammalian species and breeds, and for studying associations with economic traits. The aim of this work was to analyze milk protein genetic variation in the Original Pinzgauer, a dual-purpose (dairy and beef) cattle breed of European origin that was influenced in the past by human movements from different regions as well as by crossbreeding with Red Holstein. A total of 485 milk samples from Original Pinzgauer from Austria (n=275) and Germany (n=210) were typed at milk proteins alpha(S1)-casein, beta-casein, kappa-casein, alpha-lactalbumin, and beta-lactoglobulin by isoelectrofocusing to analyze the genetic variation affecting the protein amino acid charge. The Original Pinzgauer breed is characterized by a rather high genetic variation affecting the amino acid charge of milk proteins, with a total of 15 alleles, 12 of which were found at a frequency >0.05. The most polymorphic protein was beta-casein with 4 alleles detected. The prevalent alleles were CSN1S1*B, CSN2*A(2), CSN1S2*A, CSN3*A, LGB*A, and LAA*B. A relatively high frequency of CSN1S2*B (0.202 in the whole data set) was found, mainly occurring within the C-A(2)-B-A haplotype (in the order CSN1S1-CSN2-CSN1S2-CSN3), which seems to be peculiar to the Original Pinzgauer, possibly because the survival of an ancestral haplotype or the introgression of Bos indicus.

Metabolic compensation and depression in Alzheimer's disease.

BACKGROUND/AIMS: The aim of this study was to map metabolic compensation and depression in Alzheimer's disease (AD) on a voxel-by-voxel basis. METHODS: Twenty-one healthy elderly subjects and 25 AD patients underwent cerebral MR and FDG-PET imaging. All images were processed with SPM2, and whole-brain gray matter (GM) atrophy and hypometabolism maps were computed. Metabolic compensation and depression were assessed using Biological Parametric Mapping software. RESULTS: GM atrophy and hypometabolism mapped to similar regions, with varying degrees of severity. Significant metabolic compensation was found in the amygdala, while exceeding hypometabolism was mainly located in the posterior cingulate cortex. CONCLUSION: Metabolic depression can be due to both distant effects of atrophy and to additional hypometabolism-inducing factors, such as amyloid deposition. Conversely, metabolic compensation could reflect spared synaptic plasticity of the surviving neurons. The investigation of the metabolic compensation mechanism could help in the comprehension of the AD underlying pathology.

Functional compensation in incipient Alzheimer's disease.

Aim of this study was to investigate the functional compensation mechanism in incipient Alzheimer's disease (AD). Seventeen elderly healthy subjects and nine amnestic MCI patients with incipient AD underwent brain MR scan and 99mTc ECD SPECT. We processed all images with SPM2, we created t maps, showing the wholebrain GM atrophy and functional changes, and we properly masked them with each other in order to assess relatively preserved perfusion or depression. Incipient AD showed GM atrophy in the medial temporal and temporoparietal lobes, in the insula and in the retrosplenial cortex, and GM hypoperfusion in the medial temporal and temporoparietal lobes. Relatively preserved perfusion, we could hypothesize to be compensatory in the setting of neuronal loss, was found in the posterior cingulate, in the head of the hippocampus, in the amigdala, and in the insula bilaterally, while functional depression occurred in bilateral parahippocampal gyri. In AD, a perfusional compensatory mechanism takes place in the neocortex, while perfusional depression occurs in the medial temporal lobe. These results help understand the reactive phenomena induced by the brain to try and counteract the pathological changes of AD.

Invited review: milk protein polymorphisms in cattle: effect on animal breeding and human nutrition.

The 6 main milk proteins in cattle are encoded by highly polymorphic genes characterized by several nonsynonymous and synonymous mutations, with up to 47 protein variants identified. Such an extensive variation was used for linkage analysis with the description of the casein cluster more than 30 yr ago and has been applied to animal breeding for several years. Casein haplotype effects on productive traits have been investigated considering information on the whole casein complex. Moreover, mutations within the noncoding sequences have been shown to affect the specific protein expression and, as a consequence, milk composition and cheesemaking. Milk protein variants are also a useful tool for breed characterization, diversity, and phylogenetic studies. In addition, they are involved in various aspects of human nutrition. First, the occurrence of alleles associated with a reduced content of different caseins might be exploited for the production of milk with particular nutritional qualities; that is, hypoallergenic milk. On the other hand, the frequency of these alleles can be decreased by selection of sires using simple DNA tests, thereby increasing the casein content in milk used for cheesemaking. Furthermore, the biological activity of peptides released from milk protein digestion can be affected by amino acid exchanges or deletions resulting from gene mutations. Finally, the gene-culture coevolution between cattle milk protein genes and human lactase genes, which has been recently highlighted, is impressive proof of the nonrandom occurrence of milk protein genetic variation over the centuries.

Characterization and genetic study of the ovine alphaS2-casein (CSN1S2) allele B.

An interesting and quite complex protein pattern has been described at ovine milk proteins but the genetic control of the variation observed was assessed only in few cases. The aim of this work was to characterize the ovine alpha ( s2 )-casein (CSN1S2) B variant, first observed in the Italian Gentile di Puglia, a fine-wooled ovine breed, and to investigate its occurrence in two further breeds, the Sarda and Camosciata, which are the most widespread dairy breeds in Italy. The B variant differs from the most common form A with two amino acid exchanges: Asp(75) --> Tyr(75) and Ile(105) --> Val(105). The first substitution, resulting in a loss of a negative charge, is responsible for the higher isoelectric point of the B protein variant, which allows its detection by isoelectric focusing electrophoresis (IEF). The occurrence of CSN1S2*B in Sarda and Comisana was demonstrated. Since the Asp(75) --> Tyr(75) substitution modifies the protein electric charge, milk properties may result affected to some extent.

Relationships among functional markers, management, and husbandry in sheep: a Mediterranean case study.

Most sheep farmers are aware of the importance of monitoring animal health and well-being for profitable sheep production. Unfortunately, there are only a few benchmarked functional measures of sheep well-being but much can be gained from our understanding of other species. Moreover, comprehensive monitoring programs may be complex and relatively expensive to implement. Hence, this work reports the results of a research study on the usefulness of functional markers in measuring dairy sheep well-being, taking into account farm management and environmental conditions. The study was conducted on 11 farms breeding Italian islander sheep breeds. The husbandry and management parameters of each farm were assessed and, based on the findings, the farms were scored in ascending quality order. Flock information concerned housing, milking system, pen size, grazing hours, health management, and stockmanship. Medical history, clinical data, the most relevant haematological, chemical and biochemical parameters, as well as the haemoglobin genotype were recorded for 415 individuals. The whole data-set was analyzed by Spearman correlation and multivariate statistical procedures, showing that albumin, serum alkaline phosphatase, haematocrit, and haemoglobin were the most significant functional markers of a flock's general conditions. Haematocrit and haemoglobin reflect animal health status, while albumin and serum alkaline phosphatase are a measure of nutritional status and physical activity, respectively. These are objective parameters, which can be easily measured from blood samples and have proved to be effective for grouping to interpret animal well-being.

In vivo mapping of amyloid toxicity in Alzheimer disease.

OBJECTIVE: To study the relationship between gray matter atrophy and amyloid deposition in Alzheimer disease (AD). METHODS: Volumetric magnetic resonance (MR) and [11C]-PIB PET were acquired from 23 patients with AD and 17 healthy older persons. Standardized [11C]-PIB uptake values were coregistered to MR scans in a standard space. Decreased density of and increased [11C]-PIB uptake in the gray matter of patients with AD vs controls were assessed with both voxel-based (p < 0.05 corrected) and region-of-interest (ROI) analyses. The relationship between decreased density of and increased [11C]-PIB uptake in the gray matter was investigated with voxel-based Pearson r maps (thresholded at p < 0.05) and ROI linear regression plots. RESULTS: Atrophy mapped to the hippocampus and increased [11C]-PIB uptake to large frontal, parietal, and posterior cingulate cortical areas. ROI analysis showed the largest effect size for atrophy in the hippocampus (2.01) and amygdala (1.27) and the highest effect size for [11C]-PIB uptake in frontal (2.66), posterior cingulate/retrosplenial (2.43), insular (2.41), and temporal (2.23) regions. In the hippocampus, [11C]-PIB uptake was significantly increased, but effect size was milder (1.72). Significant correlations between atrophy and increased [11C]-PIB uptake were found in the hippocampal (r = -0.54) and amygdalar ROIs (r = -0.40) but not in the frontal, temporal, posterior cingulate/retrosplenial, insular, and caudate ROIs (r between 0.04 and 0.25). CONCLUSION: The medial temporal lobe might be highly susceptible to amyloid toxicity, whereas neocortical areas might be more resilient.

Characterization and genetic analysis of bovine alpha S1-casein I variant.

The aim of this study was to identify the molecular genetic origin underlying the I variant of alpha(s1)-casein and to develop a DNA-based test for this polymorphism as a tool for genetic analyses independent of milk sample testing. All coding exons and flanking regions of the alpha(s1)-casein gene were sequenced in DNA samples from cattle of known alpha(s1)-casein genotypes (BI, CI, II, CC), determined by isoelectric focusing of milk samples. A nucleotide substitution (A>T) in exon 11 (g.19836A>T) leads to the exchange of Glu with Asp at amino acid position 84 of the mature protein (p.Glu84Asp) and perfectly co-segregated with the presence of the alpha(s1)-casein I variant in the milk of the analysed animals. Genotyping of a total of 680 DNA samples from 31 Bos taurus and Bos indicus cattle breeds and from Bos grunniens, Bison bison and Bison bonasus by restriction fragment length polymorphism analysis revealed the occurrence of Asp at position 84 at low frequencies in Bos taurus and Bos indicus breeds and established its origin from the alpha(s1)-casein C variant (p.Glu192Gly). Ten different intragenic haplotypes in the gene region from intron 8 to intron 12 were observed by sequencing, of which two occurred in Bison bison and one in Bison bonasus only. Using available casein gene complex information, an association of Asp at position 84 to beta-casein A(2) and kappa-casein B was shown in the Bos indicus breed Banyo Gudali. Taken together, we can postulate that the alpha(s1)-casein variant I is caused by a non-synonymous nucleotide substitution in exon 11 of the gene and that it originated within Bos indicus and spread to Bos taurus subsequently.