Background There is limited evidence about the impact of specific patterns of multi-morbidity on health-related quality of life (HRQoL) from large samples of adult subjects. Methods We used data from ...the English General Practice Patient Survey 2011-2012. We defined multi-morbidity as the presence of two or more of 12 self-reported conditions or another (unspecified) long-term health problem. We investigated differences in HRQoL (EQ-5D scores) associated with combinations of these conditions after adjusting for age, gender, ethnicity, socio-economic deprivation and the presence of a recent illness or injury. Analyses were based on 831,537 responses from patients aged 18 years or older in 8,254 primary care practices in England. Results Of respondents, 23 % reported two or more chronic conditions (ranging from 7 % of those under 45 years of age to 51 % of those 65 years or older). Multimorbidity was more common among women, White individuals and respondents from socio-economically deprived areas. Neurological problems, mental health problems, arthritis and long-term back problem were associated with the greatest HRQoL deficits. The presence of three or more conditions was commonly associated with greater reduction in quality of life than that implied by the sum of the differences associated with the individual conditions. The decline in quality of life associated with an additional condition in people with two and three physical conditions was less for older people than for younger people. Multimorbidity was associated with a substantially worse HRQoL in diabetes than in other long-term conditions. With the exception of neurological conditions, the presence of a comorbid mental health problem had a more adverse effect on HRQoL than any single comorbid physical condition. Conclusion Patients with multi-morbid diabetes, arthritis, neurological, or long-term mental health problems have significantly lower quality of life than other people. People with long-term health conditions require integrated mental and physical healthcare services.
Recent studies have implicated an important role for the dorsal striatum during craving for cocaine and in cocaine-seeking after abstinence in rats.
We compared the effects of pharmacological ...inactivation of mesencephalic dopamine (DA) cell body regions and dorsal vs ventral striatal terminal fields in an animal model of relapse after chronic cocaine self-administration.
Rats self-administered cocaine for 2 h/day for ten sessions, followed by 2 weeks of abstinence (i.e., no extinction training). Immediately before being returned to the self-administration chamber, we assessed the effects of gamma-aminobutyric acid agonist inhibition of midbrain DA regions (substantia nigra SN and ventral tegmental area VTA) and striatum (dorsolateral caudate-putamen, nucleus accumbens core, and nucleus accumbens shell) on relapse to cocaine-seeking in the absence of reinforcement. Further testing examined daily extinction responding subsequent to the initial relapse test.
Inactivation of the dorsal caudate-putamen and midbrain regions attenuated cocaine seeking, while inactivation of the ventral striatum had no such effects. However, subsequent sessions under extinction conditions revealed a rebound in cocaine seeking in animals that had undergone inactivation in all regions except the dorsolateral caudate-putamen.
The dorsal but not ventral striatum plays a critical role in cocaine seeking immediately after abstinence. These data support the theory that chronic cocaine may shift activity from the ventral to dorsal striatum during drug seeking under certain conditions. While not necessary at the time of relapse, the ventral striatum appears to be involved in processing critical information of the relapse event.
The Cold Atom Laboratory on the International Space Station produces ultracold gases of rubidium and potassium in a tight magnetic trap near the surface of a magnetic chip. In order to use these ...samples in long-duration field-free experiments, the atoms must be moved away from the chip, expanded to larger volume, and released from the trap. We describe how these goals can be achieved using quasi-adiabatic techniques. For rubidium atoms, we demonstrate a displacement of 0.6 mm and expansion into a trap with a mean oscillation frequency of 6.4 Hz. The center-of-mass release velocity and the condensate expansion velocity are about 0.2 mm/s each. An unexpectedly large background magnetic field gradient is observed, which limits the usable interaction time for the released atoms.
▶ Novel bacterial expression system for host defense peptides. ▶ Scalable, simplified 2-step purification. ▶ Large-scale expression of peptides as small as 9 amino acids in length. ▶ Successful ...application of this method to peptides already in clinical trials. ▶ Suitable for large-scale production of antimicrobial peptides and host defense peptides under GMP for therapeutic use.
Cationic antimicrobial host defense peptides (HDPs) combat infection by directly killing a wide variety of microbes, and/or modulating host immunity. HDPs have great therapeutic potential against antibiotic-resistant bacteria, viruses and even parasites, but there are substantial roadblocks to their therapeutic application. High manufacturing costs associated with amino acid precursors have limited the delivery of inexpensive therapeutics through industrial-scale chemical synthesis. Conversely, the production of peptides in bacteria by recombinant DNA technology has been impeded by the antimicrobial activity of these peptides and their susceptibility to proteolytic degradation, while subsequent purification of recombinant peptides often requires multiple steps and has not been cost-effective. Here we have developed methodologies appropriate for large-scale industrial production of HDPs; in particular, we describe (i) a method, using fusions to SUMO, for producing high yields of intact recombinant HDPs in bacteria without significant toxicity and (ii) a simplified 2-step purification method appropriate for industrial use. We have used this method to produce seven HDPs to date (IDR1, MX226, LL37, CRAMP, HHC-10, E5 and E6). Using this technology, pilot-scale fermentation (10
L) was performed to produce large quantities of biologically active cationic peptides. Together, these data indicate that this new method represents a cost-effective means to enable commercial enterprises to produce HDPs in large-scale under Good Laboratory Manufacturing Practice (GMP) conditions for therapeutic application in humans.
A change in motivational state does not guarantee a change in operant behaviour. Only after an organism has had contact with an outcome while in a relevant motivational state does behaviour change, a ...phenomenon called incentive learning. While ample evidence indicates that this is true for primary reinforcers, it has not been established for conditioned reinforcers. We performed an experiment with rats where lever-presses were reinforced by presentations of an audiovisual stimulus that had previously preceded food delivery; in the critical experimental groups, the audiovisual stimulus was then paired a single time with a strong electric shock. Some animals were reexposed to the audiovisual stimulus. Lever-presses yielding no outcomes were recorded in a subsequent test. Animals that had been reexposed to the audiovisual stimulus after the aversive training responded less than did those that had not received reexposure. Indeed, those animals that were not reexposed did not differ from a control group that received no aversive conditioning of the audiovisual stimulus. Moreover, these results were not mediated by a change in the food’s reinforcement value, but instead reflect a change in behaviour with respect to the conditioned reinforcer itself. These are the first data to indicate that the affective value of conditioned stimuli, like that of unconditioned ones, is established when the organism comes into contact with them.
Titan's Surface Brightness Temperatures Jennings, D. E; Flasar, F. M; Kunde, V. G ...
The Astrophysical journal,
02/2009, Letnik:
691, Številka:
2
Journal Article
Background
Hypertension is a common problem in older cats, most often associated with chronic kidney disease (CKD). Cross‐sectional studies have suggested that blood pressure in cats increases with ...age.
Hypothesis/Objectives
To determine whether blood pressure in cats increases with age and whether this occurs independently of the presence of CKD. To investigate risk factors for developing hypertension.
Animals/Subjects
Two hundred and sixty‐five cats with CKD and 133 healthy cats ≥9 years were retrospectively identified.
Methods
Four groups were created according to status at initial evaluation (CKD or healthy) and blood pressure at the last included visit (normotensive NT or developed hypertension DH): Healthy‐NT, Healthy‐DH, CKD‐NT and CKD‐DH. Systolic blood pressure (SBP) over time slopes were compared with 0 and between groups. Risk factors for the development of hypertension were investigated, and associations of biochemical and clinical variables with SBP were examined.
Results
Cats that were hypertensive at CKD diagnosis (n = 105) were not included in further analyses. Twenty‐seven cats with CKD and 9 healthy cats developed hypertension ≥3 months after diagnosis of CKD or their first visit. Systolic blood pressure significantly increased with age in all cats (P < .001). Healthy cats were at less risk than cats with CKD to become hypertensive (hazard ratio 0.2, P < .001), with creatinine being an independent risk factor for the development of hypertension.
Conclusions and Clinical Importance
The high prevalence of hypertension in azotemic cats in this study shows the importance of monitoring of SBP in elderly cats, and in particular in cats with CKD.
The aims of our study were to identify serum biomarkers that distinguish pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) patients from benign pancreatic disease patients and healthy ...subjects, and to assess the effects of jaundice on biomarker performance.
Isobaric tags for relative and absolute quantification were used to compare pooled serum and pancreatic juice samples from a test set of 59 and 25 subjects, respectively. Validation was undertaken in 113 independent subjects.
Candidate proteins Complement C5, inter-α-trypsin inhibitor heavy chain H3, α1-β glycoprotein and polymeric immunoglobulin receptor were elevated in cancer, as were the reference markers CA19-9 and Reg3A. Biliary obstruction had a significant effect on the performance of the markers, in particular within the PDAC group where the presence of jaundice was associated with a significant increase in the levels of all six proteins (P<0.01). Consequently, in the absence of jaundice, proteins showed reduced sensitivity for PDAC patients over benign subjects and healthy controls (HCs). Similarly, in the presence of jaundice, markers showed reduced specificity for PDAC patients over benign subjects with jaundice. Combining markers enabled improved sensitivity for non-jaundiced PDAC patients over HCs and improved specificity for jaundiced PDAC patients over jaundiced benign disease subjects.
The presence-absence of jaundice in the clinical scenario severely impacts the performance of biomarkers for PDAC diagnosis and has implications for their clinical translation.
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