The effect of task on object processing revealed by EEG decoding.

Recent studies showed that task demand affects object representations in higher-level visual areas and beyond but not so much in earlier areas. There are, however, limitations in those studies including the relatively weak manipulation of task due to the use of familiar real-life objects, the low temporal resolution in functional magnetic resonance imaging (fMRI) and the emphasis on the amount and not the source of information carried by brain activations. In the current study, observers categorised images of artificial objects in one of two orthogonal dimensions, shape and texture, while their brain activity was recorded with electroencephalogram (EEG). Results showed that object processing along the texture dimension was affected by task demand starting from a relatively late time (320- to 370-ms time window) after image onset. The findings are consistent with the view that task exerts an effect on the later phases of object processing.

Dietary supplementation with mannan oligosaccharide and clinoptilolite modulates innate and adaptive immune parameters of weaned pigs.

The aim of this study was to assess modulatory effects of dietary supplements mannan oligosaccharide (MOS) and clinoptilolite (CPL) as potential alternatives to antibiotic growth promoters (AGP) given to 4-week old pigs at weaning (Day 0) on their innate/adaptive immunity by determining: alterations in C-reactive protein (CRP) and haptoglobin (HpG) serum levels, efficiency of blood monocytes (MO) and neutrophilic granulocytes (GR) for in vitro phagocytosis (PHC)/microbicidity (MBC) and proportion of extrathymic double positive CD4 CD8 (CD4+CD8+) T cells throughout 35 days of the study. Neither MOS nor CPL changed the serum concentrations of CRP, whereas that of HpG was significantly increased in the CPL supplemented pigs (p<0.05) at Day 35. Activity of PHA of GR was significantly increased by both dietary supplements (p<0.05) from Day 7 to Day 35. Also, the GR from pigs fed with both supplements had significantly increased MBC at Day 7 (p<0.05), but at Day 35 such an increase was observed only for CPL. The in vitro PHC/MBC of MO did not change in either group of supplemented pigs. The pigs supplemented with MOS had a significantly higher proportion of CD4+CD8+ T lymphocytes at Day 28 (p<0.05). Although both supplements showed a promising ability to stimulate rather innate than adaptive cellular immunity, it does not appear that any solely applied natural substance such as MOS or CPL in the current study could be a competitive alternative to conventional AGP for improving health and promoting growth in weaned pigs.

The onset of puberty in Cameroon Dwarf goats kept as pets in northwestern Croatia.

The aim of this study was to determine onset of puberty in Cameroon Dwarf goats (CDGs) kept as pets in northwestern Croatia by determining progesterone (PGS) and insulin-like growth factor-I (IGF-I) levels in the blood by RIA methods. The first cyclic ovarian activity was estimated according to hormone profiles as determined in CDG in a moderate climate environment. Sixteen female CDG kids were kept in stables with access to pasture which provided space for exercise. The goat kids born in winter (December-January-February), spring (March-April-May), summer (June-July-August) and autumn (September-October-November) were assigned into four groups according to the season of the year of birth (n = 4 in each group). At 75 days of age at the initiation of the study, they weighed between 3.2 and 5.1 kg (4.24 ± 0.53 kg). The onset of ovulatory activity was determined by PGS and IGF-I serum concentrations every 10 days starting from 75 days to 155 days of age. The onset of puberty in CDG kids occurred on average at 141.15 ± 2.66 days of age, but varied depending on the season of birth. All CDG kids born during summer were in heat by 155 days of age. In the other groups (kids born in autumn, winter or spring), one goat in each group was not in heat. Changes in blood serum PGS and IGF-I concentrations during prepubertal and pubertal periods could aid in the evaluation of reproductive status and determination of the onset of puberty in CDG during all seasons of the year in a moderate climate region.

Monitoring of libido and semen quality parameters in melatonin-treated French alpine bucks during the non-breeding season.

The aim of this study was to investigate the effects of exogenous melatonin on libido and semen quality parameters in bucks during the non-breeding season. Twelve bucks of the French alpine breed from 1.5 to 4 years of age were assigned into melatonin (MG) and control (CG) groups, with 6 bucks in each group. The experimental period was 3 months (March-May), divided into six periods of 15 days each. The bucks in the MG group received four melatonin implants at the end of March. Two semen samples were taken from the bucks by artificial vagina once per week and their libido estimated. Volume and spermatozoa concentration, their mass motility and motility, proportion of live and total abnormal and forms with abnormal head and tail were determined in the obtained ejaculate samples. The total number of spermatozoa and functional spermatozoa fraction in the ejaculate was also calculated. The MG bucks had significantly higher mass motility and motility of spermatozoa in the first half of April, and a higher proportion of live spermatozoa in the first and second half of April (p < .05). Differences in libido intensity were not significant. The results indicated that the application of melatonin significantly improved the qualitative parameters of semen in bucks, as seen in increased mass motility, motility of spermatozoa and proportion of live spermatozoa shortly following melatonin insertion. Therefore, the results of the current study are novel regarding the use of melatonin treatment during the non-breeding season to improve the qualitative parameters of ejaculates in bucks.

Influence of Body Condition on Serum Metabolic Indicators of Lipid Mobilization and Oxidative Stress in Dairy Cows During the Transition Period.

The objectives of this study were to examine the influence of body condition of cows on metabolic and antioxidative status, as well as to investigate the relationship between metabolic indicators of lipid mobilization and oxidative stress during transition period. The study was conducted on 24 Holstein-Friesian dairy cows divided into 2 groups according to their body condition score (BCS) as optimal (n = 12; BCS from 3.25 to 3.75) or adipose (n = 12; BCS ≥4). Metabolic status (glucose, triglycerides, total cholesterol, HDL cholesterol, NEFA and BHB), paraoxonase-1 (PON1) and apolipoprotein A-I (ApoA-I) were analysed in sera taken on days -30, -10, -2, 0, 5, 12, 19, 26 and 60 relative to parturition. Adipose cows had significantly higher glucose concentration at parturition being significantly decreased after parturition on days 12 and 19. Total cholesterol and HDL-C concentrations were the lowest at parturition and significantly higher on days 26 and 60 after parturition in both groups of cows. Both investigated groups had significantly higher NEFA concentration from parturition until day 19 after parturition, indicating energy deficit and an increased lipid mobilization after calving. There were no significant differences in BHB concentration during transition period in both groups. No significant differences were found in PON1 activity and ApoA-I concentration during transition period in both groups of cows. However, in adipose cows, although not significantly different, PON1 was decreased from calving until day 19 after parturition indicating a disturbance in antioxidative status in adipose cows. PON1 significantly positively correlated with total cholesterol and HDL-C concentrations and negatively with NEFA indicating a strong relationship of PON1 with lipid metabolism. Significant positive correlation between NEFA and BHB in both groups of cows points out on energy deficit during transition period that cows tend to overcome by lipid mobilization providing alternative source of energy needed for parturition and lactation.

Identifying human-rhesus macaque gene orthologs using heterospecific SNP probes.

We genotyped a Chinese and an Indian-origin rhesus macaque using the Affymetrix Genome-Wide Human SNP Array 6.0 and cataloged 85,473 uniquely mapping heterospecific SNPs. These SNPs were assigned to rhesus chromosomes according to their probe sequence alignments as displayed in the human and rhesus reference sequences. The conserved gene order (synteny) revealed by heterospecific SNP maps is in concordance with that of the published human and rhesus macaque genomes. Using these SNPs' original human rs numbers, we identified 12,328 genes annotated in humans that are associated with these SNPs, 3674 of which were found in at least one of the two rhesus macaques studied. Due to their density, the heterospecific SNPs allow fine-grained comparisons, including approximate boundaries of intra- and extra-chromosomal rearrangements involving gene orthologs, which can be used to distinguish rhesus macaque chromosomes from human chromosomes.

Development of a Quantitative Digital Urinalysis Tool for Detection of Nitrite, Protein, Creatinine, and pH.

This paper presents a cost-effective, quantitative, point-of-care solution for urinalysis screening, specifically targeting nitrite, protein, creatinine, and pH in urine samples. Detecting nitrite is crucial for the early identification of urinary tract infections (UTIs), while regularly measuring urinary protein-to-creatinine (UPC) ratios aids in managing kidney health. To address these needs, we developed a portable, transmission-based colorimeter using readily available components, controllable via a smartphone application through Bluetooth. Multiple colorimetric detection strategies for each analyte were identified and tested for sensitivity, specificity, and stability in a salt buffer, artificial urine, and human urine. The colorimeter successfully detected all analytes within their clinically relevant ranges: nitrite (6.25-200 µM), protein (2-1024 mg/dL), creatinine (2-1024 mg/dL), and pH (5.0-8.0). The introduction of quantitative protein and creatinine detection, and a calculated urinary protein-to-creatinine (UPC) ratio at the point-of-care, represents a significant advancement, allowing patients with proteinuria to monitor their condition without frequent lab visits. Furthermore, the colorimeter provides versatile data storage options, facilitating local storage on mobile devices or in the cloud. The paper further details the setup of the colorimeter's secure connection to a cloud-based environment, and the visualization of time-series analyte measurements in a web-based dashboard.

Nanoscale plasmonic interferometers for multispectral, high-throughput biochemical sensing.

In this work, we report the design, fabrication, and characterization of novel biochemical sensors consisting of nanoscale grooves and slits milled in a metal film to form two-arm, three-beam, planar plasmonic interferometers. By integrating thousands of plasmonic interferometers per square millimeter with a microfluidic system, we demonstrate a sensor able to detect physiological concentrations of glucose in water over a broad wavelength range (400-800 nm). A wavelength sensitivity between 370 and 630 nm/RIU (RIU, refractive index units), a relative intensity change between ~10(3) and 10(6) %/RIU, and a resolution of ~3 × 10(-7) in refractive index change were experimentally measured using typical sensing volumes as low as 20 fL. These results show that multispectral plasmonic interferometry is a promising approach for the development of high-throughput, real-time, and extremely compact biochemical sensors.

An early perceptual locus of absolute pitch.

Absolute pitch (AP) refers to the naming of musical tone without external reference. The influential two-component model states that AP is limited by the late-emerging pitch labeling process only and not the earlier perceptual and memory processes. Over the years, however, support for this model at the neural level has been mixed with various methodological limitations. Here, the electroencephalography responses of 27 AP possessors and 27 non-AP possessors were recorded. During both name verification and passive listening, event-related potential analyses showed a difference between AP and non-AP possessors at about 200 ms in their response toward tones compared with noise stimuli. Multivariate pattern analyses suggested that pitch naming was subserved by a series of transient processes for the first 250 ms, followed by a stage-like process for both AP and non-AP possessors with no group differences between them. These findings are inconsistent with the predictions of the two-component model, and instead suggest the existence of an early perceptual locus of AP.

Effect of preventive intrauterine ozone application on reproductive efficiency in Holstein cows.

The aim of the research was to determine the influence of preventive application of two different ozone preparations on reproductive efficiency in dairy cows with physiological puerperium. The research was conducted on 404 Holstein cows aged 2-8 years, divided into three groups. The first group consisted of cows treated using 6 intrauterine ozone pearls (RIPROMED OVULI O(3) (®) , Novagen, Italy) at once. The second group consisted of cows treated with ozone foam spray (RIGER SPRAY(®) , Novagen, Italy) application in the body of uterus for 5 s, and the third group was the control group. Cows from the first two groups were observed and treated during early puerperium, 24-48 h after parturition. To assess the reproductive performance of Holstein cows, interval from calving to first insemination (days open to first service, DOFS), interval from calving to pregnancy (days open to pregnancy, DOP), relative pregnancy rate (%), first service conception rate (FSCR, %) and all service conception rate (ASCR, %) were measured. The estimate of hazard ratio (HR) for group B relative to group C for DOFS was 0.62 (p = 0.0002), implying that the relative rate of first service decreased in the control group by 38%. The estimate of HR for group B relative to group C for DOP was 0.65 (p = 0.0006), implying that the relative rate of pregnancy decreased in group C by 35%. Cows treated with Riger spray (group B) became pregnant earlier and had better FSCR and ASCR. It is supposed that the form of ozone preparations and the amount of active substance were decisive. A conclusion may be made that preventive ozone intrauterine application during early puerperal period, especially the foaming form of ozone preparations (spray), improved the reproductive efficacy in dairy cows.

Rate of utilization of physical therapy after common pediatric elbow fractures.

Supracondylar, medial epicondyle and lateral condyle fractures are the three most common elbow fractures in pediatric patients. There is a paucity of literature discussing the utilization of physical therapy following these injuries. The purpose of the current study was to determine the rate of utilization of physical therapy after these injuries as well as determine factors that may affect the need for physical therapy after common elbow fractures in pediatric patients. We retrospectively chart reviewed all pediatric elbow fractures that were managed at a major pediatric health system from 2013 to 2020. This study included patients under the age of 18 years and utilized International Classification of Diseases (ICD)-9, ICD-10 and Current Procedural Terminology codes to identify patients. Descriptive statistics, chi-square test and multivariate analyses were performed to compare differences between groups. This study included 2037 patients. Overall, 90 patients (4.4%) received a physical therapy referral at an average time of 90.1 (± 54.6) days between discharge and referral. The rate of physical therapy was 2.7% after nonoperative and 6.3% after operative treatment (P < 0.01). Overall, patients that sustained medial epicondyle fractures were prescribed physical therapy at a higher rate (19.8%) than supracondylar (1.4%) or lateral condyle fractures (5.0%) (P < 0.01). For each fracture type, physical therapy utilization was higher among those treated operatively versus those treated nonoperatively (P < 0.01). Physical therapy is more commonly prescribed for patients with medial epicondyle fractures and patients that received operative management. Additional research is needed to determine clinical indications and efficacy of physical therapy after common elbow fractures in pediatric patients.

Toward a Quantitative Colorimeter for Point-of-Care Nitrite Detection.

This paper reports on a low-cost, quantitative, point-of-care solution for the early detection of nitrite, a common biomarker for urinary tract infections (UTIs). In a healthy individual, nitrite is not found in the urine. However, a subject with a suspected UTI will produce nitrite in their urine since the bacteria present will convert nitrate into nitrite. Traditionally, nitrite is monitored by urinary dipsticks that are either read by eye or using a reflectance spectrophotometer. Both methods provide a semiquantitative positive or negative result at best. In this paper, we described a novel, affordable, portable transmission-based colorimeter for the quantitative measurement of nitrite. A unique permutation of the Griess reaction was optimized for the clinical detection of nitrite in urine and is reported. By using nitrite spiked in a salt buffer, artificial, and human urine samples, the performance of the colorimeter was evaluated against dipsticks read using two commercial dipstick analyzers, Urisys 1100 (Roche Diagnostics) and Clinitek Status+ (Siemens Medical Solutions). The colorimeter was able to detect the clinically relevant range of nitrite from 0.78 to 200 µM in a salt buffer. The detection limit in artificial urine was determined as 1.6 µM, which is ∼16× more sensitive than commercial dipstick reflectance analyzers, enabling the possibility for earlier detection of urinary infections. The colorimeter is assembled using off-the-shelf components (<$80) and controlled by a smartphone application via low-energy bluetooth. It has a built-in color correction algorithm and is designed to enable for a turbidity correction in samples containing bacteria or other cellular debris as well. The mobile application can display the nitrite concentration for a single sample or display the results over a period of time. Tracking urinalysis results longitudinally can help identify trends such as increases in nitrite concentrations over an individual's baseline and identify possible infections earlier. While the detection of nitrite was showcased here, this portable analyzer can be expanded to other colorimetric-based chemistries to detect a panel of biomarkers, which can improve the overall sensitivity and specificity of the desired assay.

Effects of dietary clinoptilolite on reproductive performance, serum progesterone and insulin-like growth factor-1 concentrations in dairy cows during pregnancy and lactation.

The objective of this study was to evaluate the effects of dietary zeolite clinoptilolite on re- productive performance, serum progesterone and insulin-like growth factor 1 (IGF-1) concentra- tions in 78 Holstein Friesian (HF) cows during pregnancy and lactation. The cows were divided into two groups comprising 40 (control group; CON) and 38 (CPL group) cows. To assess repro- ductive performance of HF cows the following variables were registered: the interval from calv- ing to first insemination (days open to first service, DFS), the interval from calving to pregnancy (days open to pregnancy, DOP), and the number of services per pregnancy (NSP). The average values of progesterone (5.64±0.59 ng/mL vs. 5.16±0.64 ng/mL) were not statistically different (p⟨0.05) and IGF-1 levels (400.17±17.72 ng/mL vs. 348.36±20.39 ng/mL) were higher in the CON than in the CPL group which received 50 g of clinoptilolite twice a day. However, in the CPL group ovarian cyclity resumed on days 40 and 60 postpartum. In addition, DFS (p⟨0.05) and DOP (p>0.05) were shorter in the CPL than in the CON group (115.1±19.9 and 137.5±36.3 days vs. 124.2±17.3 and 143.8±33.5 days, respectively). During 305 days of lactation, milk production was higher in the CPL vs. CON (8325.5±628.8 kg vs. 8050±586.8 kg). The NSP was lower in the CPL than in CON group (1.91 vs. 2.14). The dietary clinoptilolite supplement had a positive in- fluence on milk yield, exhibited modulating effects on endocrine status of dairy cows, and im- proved reproductive performance, with the decreased NSP, and fewer DFS and DOP.

The influence of exogenous melatonin on antioxidative status in seminal plasma and spermatozoa in French Alpine bucks during the nonbreeding season.

Research data regarding exogenous melatonin effects on buck semen antioxidative status during the breeding and nonbreeding seasons are scarce or missing. The aim of this study was to investigate the effect of melatonin implants on the activity and ratios of antioxidative enzymes and on malondialdehyde concentrations in the seminal plasma and spermatozoa of French Alpine bucks during the 3 mo of the nonbreeding season. Two groups of randomly assigned bucks were either treated with melatonin (n = 6) or served as controls (n = 6). Semen samples were collected weekly, seminal plasma was separated from spermatozoa, and activities of glutathione peroxidase (GSH-Px), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and the concentration of malondialdehyde were determined. The melatonin-treated bucks had significantly higher CAT/SOD and GSH-Px/SOD ratios, but a significantly lower GR/GSH-Px ratio in seminal plasma and spermatozoa during the different periods of the nonbreeding season. In conclusion, exogenous melatonin influenced the activities of all ratios and some single antioxidative enzymes tested in bucks' seminal plasma and spermatozoa. Here we provide the first evidence derived from an intervention, that is, melatonin treatment, which affects antioxidative enzymes ratios in the semen of bucks, and could thus be recommended as an indicator of oxidative stress severity and antioxidative status of semen.

Total synthesis of the marine alkaloid halichlorine: development and use of a general route to chiral piperidines.

The total synthesis of the marine alkaloid halichlorine is described, based on an approach that involves constructing the fully substituted asymmetric center at an early stage. The five-membered ring is formed by 5-exo-trig radical cyclization and the unsaturated six-membered ring by a process that formally represents a sequential combination of conjugate addition and S(N)2' displacement-a method that is general for making bicyclic compounds with nitrogen at a ring fusion position. A formal synthesis of (+)-halichlorine is also reported, based on the development of a general method for preparing optically pure piperidines. The key step of this method, which was used to make one of our intermediates, is the Claisen rearrangement of a 4-vinyloxy-3,4-dihydro-2H-pyridine-1-carboxylic acid benzyl ester. Such O-vinyl compounds are easily generated in situ from the corresponding alcohols, which are themselves readily assembled from serine and terminal acetylenes.

Sensitivity to configural information and expertise in visual word recognition.

Holistic processing has been regarded as a marker of perceptual expertise for many object categories. However, visual word processing, a common form of perceptual expertise in the population, is traditionally considered part-based instead of holistic, and whether it involves holistic processing remains inconclusive. In 4 experiments, we examined a well-known yet less studied indicator of holistic word processing-observers' sensitivity to changes in configural information of objects. A paradigm was designed with 2 crucial elements: specific requirement to process configural information within a word and an inversion manipulation. Experiments 1 and 2 showed that experienced observers were more sensitive to configural changes when words were presented in the familiar upright than unfamiliar inverted orientation. Of importance, such an inversion effect was correlated with one's fluency in word recognition in 1 of the conditions (nonnative Chinese readers viewing Chinese characters) where there was a larger variability in word recognition fluency. Experiments 3 and 4 compared sensitivity to configural and component changes in word processing, showing that expert readers were more sensitive to configural changes than component changes (defined as line thickness of parts) in words. The current findings suggest that, similar to face recognition and other domains of perceptual expertise, word recognition involves holistic processing. Instead of being a hallmark of face recognition, holistic processing is a general expertise marker shared by different domains of perceptual expertise. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Age-related differences of semen quality, seminal plasma, and spermatozoa antioxidative and oxidative stress variables in bulls during cold and warm periods of the year.

The aims of this study were to determine the presence and quantities of antioxidative status and oxidative stress (OS) variables in the seminal plasma and spermatozoa of bulls of varying age during cold and warm periods of the year, and to establish the correlation of these variables with semen quality parameters. The study was conducted on two groups each comprising nine Simmental bulls: one group contained younger animals (aged 2 to 4 years) and the second older animals (aged 5 to 10 years). Semen samples were collected using an artificial vagina for biochemical analysis. Seminal plasma and spermatozoa activities of total superoxide dismutase (TSOD), manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), selenium-dependent glutathione peroxidase, reduced glutathione and concentrations of total protein (TP), thiobarbituric acid reactive substances (TBARS) and protein carbonyl content (PCC) were determined. Several antioxidants in seminal plasma were also determined: total glutathione peroxidase (TGSH-Px), selenium-independent glutathione peroxidase (Non-SeGSH-Px), uric acid, albumins (ALB) and alkaline phosphatase (ALP). Significantly higher spermatozoa motility was observed during the cold v. warm period, and a significantly higher volume and total number of spermatozoa per ejaculate was observed in older than in younger bulls. Significantly higher values of ALP, TP and ALB were found in seminal plasma of older bulls than in younger bulls during the warm period. The seminal plasma of younger bulls showed significantly higher activities of TSOD, MnSOD, CuZnSOD, TGSH-Px and Non-SeGSH-Px. Younger bulls had significantly higher PCC concentration and activity of CAT in seminal plasma than older bulls during the cold period. Significantly higher concentrations of PCC and TBARS, and activities of TSOD, MnSOD and CuZnSOD were established in spermatozoa of the younger than in older bulls during the warm period. It could be concluded that antioxidative and OS variables differ significantly depending on bull age and time of year. Younger bulls were more sensitive to elevated ambient temperatures during the warm period, when the higher enzymatic antioxidative protection in seminal plasma and spermatozoa were insufficient to counteract the intensive oxidative processes in spermatozoa, which eventually resulted in decreased spermatozoa motility. The estimation of antioxidative and OS variables in seminal plasma and spermatozoa may have practical value for the assessment of bull semen quality.

A highly efficient synthesis of potent and selective butyrolactam inhibitors of 11beta-HSD1.

A convergent synthesis of structurally novel butyrolactam 11beta-HSD1 inhibitors is described. The approach features an efficient Ireland-Claisen reaction to construct a highly substituted aldehyde building block which is converted to a lactam via a tandem reductive amination/cyclization sequence. The generality of the synthetic sequence is demonstrated during the preparation of two additional potent 11beta-HSD1 inhibitors.

Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies.

OBJECT: Convection-enhanced delivery (CED) is an increasingly used novel local/regional delivery method targeted directly to tissue. It relies on a continuous pressure gradient for distribution of therapeutic agents into the interstitial space, with administration of the infusate over a few days. Cintredekin besudotox (also known as IL13- PE38QQR) is a recombinant chimeric cytotoxin consisting of interleukin-13 and a truncated exotoxin produced by the Pseudomonas aeruginosa bacterium, which targets malignant glioma cells. METHODS: Cintredekin besudotox was administered via intraparenchymal CED after resection of supratentorial recurrent malignant glioma. The safety and toxicity profile was reviewed for 53 patients in whom infusion catheters had been placed; 51 of them received CED of the study drug. Adverse events were categorized based on time of onset in relation to CED, and the causal relationship with catheter placement or delivery of cintredekin besudotox. Catheters were placed in 53 patients, although only 51 of them received cintredekin besudotox. Most adverse events related to catheter placement or the study drug originated from the central nervous system. Three symptomatic windows were defined: the first one was between surgical procedure and CED; the second was during CED and up to 1 week after its completion; and the third window was 2 to 10 weeks after treatment. Those windows generally reflected adverse events related to surgical procedures, mass effect from infusate, and drug effect on tumor-infiltrated and normal brain parenchyma, respectively. CONCLUSIONS: The symptomatic windows identified in this study apply to any CED clinical trials, particularly those in which chimeric cytotoxins are used, and will help to determine the most likely underlying pathophysiological process causing symptoms. This information, in turn, will help to prevent adverse events or minimize their severity. Those events also have implications for dose escalation and outcome measures.

The impact of somatic and cognitive disorders on the functional status of the elderly.

To estimate the relative effects of coexisting nondementia illnesses on the probability of functional disability, depending on the presence of cognitive impairment or dementia, we used data from the baseline case-control assessment of a longitudinal study of aging and dementia. Our study included 668 subjects (345 nondemented, 98 cognitively impaired, and 225 demented), aged 75 and older. Demented subjects had greater disability prevalence on all specific instrumental activities of daily living (IADL) and activities of daily living (ADL) items than cognitively impaired subjects who, in turn, had greater disability than nondemented subjects. Somatic illnesses were found to be associated with particular tasks in item specific models; decreasing MMSE was strongly associated with the probability of IADL and ADL disability, which increased dramatically in the presence of somatic illnesses among cognitively impaired as well as demented subjects. Attention to illnesses among cognitively impaired and demented people may shed light on remediable factors crucial to their daily functioning.