Constipation is one of the most common problems in patients receiving palliative care and can cause extreme suffering and discomfort. The aims of this study are to raise awareness of constipation in ...palliative care, provide clear, practical guidance on management and encourage further research in the area. A pan-European working group of physicians and nurses with significant experience in the management of constipation in palliative care met to evaluate the published evidence and produce these clinical practice recommendations. Four potentially relevant publications were identified, highlighting a lack of clear, practical guidance on the assessment, diagnosis and management of constipation in palliative care patients. Given the limited data available, our recommendations are based on expert clinical opinion, relevant research findings from other settings and best practice from the countries represented. Palliative care patients are at a high risk of constipation, and while general principles of prevention should be followed, pharmacological treatment is often necessary. The combination of a softener and stimulant laxative is generally recommended, and the choice of laxatives should be made on an individual basis. The current evidence base is poor and further research is required on many aspects of the assessment, diagnosis and management of constipation in palliative care.
Data on the possible association between depressive disorders and inflammatory markers are scarce and inconsistent. We investigated whether subjects with depressive mood had higher levels of a wide ...range of inflammatory markers involved in coronary heart disease (CHD) incidence and examined the contribution of these inflammatory markers and depressive mood to CHD outcome.
We built a nested case-referent study within the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study of healthy middle-aged men from Belfast and France. We considered the baseline plasma sample from 335 future cases (angina pectoris, nonfatal myocardial infarction, coronary death) and 670 matched controls (2 controls per case). Depressive mood characterized men whose baseline depression score (13-item modification of the Welsh depression subscale) was in the fourth quartile (mean score, 5.75; range, 4 to 12). On average, men with depressive mood had 46%, 16%, and 10% higher C-reactive protein, interleukin-6, and intercellular adhesion molecule-1 levels, respectively, independently of case-control status, social characteristics, and classic cardiovascular risk factors; no statistical difference was found for fibrinogen. The odds ratios of depressive mood for CHD were 1.35 (95% CI, 1.05 to 1.73) in univariate analysis and 1.50 (95% CI, 1.04 to 2.15) after adjustment for social characteristics and classic cardiovascular risk factors. The latter odds ratio remained unchanged when each inflammatory marker was added separately, and in this analysis, each inflammatory marker contributed significantly to CHD event risk.
These data support an association of depressive mood with inflammatory markers and suggest that depressive mood is related to CHD even after adjustment for these inflammatory markers.
The uncertainties and sources of variation in projected impacts of climate change on agriculture and terrestrial ecosystems depend not only on the emission scenarios and climate models used for ...projecting future climates, but also on the impact models used, and the local soil and climatic conditions of the managed or unmanaged ecosystems under study. We addressed these uncertainties by applying different impact models at site, regional and continental scales, and by separating the variation in simulated relative changes in ecosystem performance into the different sources of uncertainty and variation using analyses of variance. The crop and ecosystem models used output from a range of global and regional climate models (GCMs and RCMs) projecting climate change over Europe between 1961-1990 and 2071-2100 under the IPCC SRES scenarios. The projected impacts on productivity of crops and ecosystems included the direct effects of increased CO₂ concentration on photosynthesis. The variation in simulated results attributed to differences between the climate models were, in all cases, smaller than the variation attributed to either emission scenarios or local conditions. The methods used for applying the climate model outputs played a larger role than the choice of the GCM or RCM. The thermal suitability for grain maize cultivation in Europe was estimated to expand by 30-50% across all SRES emissions scenarios. Strong increases in net primary productivity (NPP) (35-54%) were projected in northern European ecosystems as a result of a longer growing season and higher CO₂ concentrations. Changing water balance dominated the projected responses of southern European ecosystems, with NPP declining or increasing only slightly relative to present-day conditions. Both site and continental scale models showed large increases in yield of rain-fed winter wheat for northern Europe, with smaller increases or even decreases in southern Europe. Site-based, regional and continental scale models showed large spatial variations in the response of nitrate leaching from winter wheat cultivation to projected climate change due to strong interactions with soils and climate. The variation in simulated impacts was smaller between scenarios based on RCMs nested within the same GCM than between scenarios based on different GCMs or between emission scenarios.
Bone metastases are devastating complications of cancer. They are particularly common in prostate cancer (PCa), represent incurable disease, and are refractory to immunotherapy. We seek to define ...distinct features of the bone marrow (BM) microenvironment by analyzing single cells from bone metastatic prostate tumors, involved BM, uninvolved BM, and BM from cancer-free, orthopedic patients, and healthy individuals. Metastatic PCa is associated with multifaceted immune distortion, specifically exhaustion of distinct T cell subsets, appearance of macrophages with states specific to PCa bone metastases. The chemokine CCL20 is notably overexpressed by myeloid cells, as is its cognate CCR6 receptor on T cells. Disruption of the CCL20-CCR6 axis in mice with syngeneic PCa bone metastases restores T cell reactivity and significantly prolongs animal survival. Comparative high-resolution analysis of PCa bone metastases shows a targeted approach for relieving local immunosuppression for therapeutic effect.
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•An immune-suppressive microenvironment characterizes bone metastatic prostate cancer•Infiltrating T cells are exhausted and dysfunctional•Inflammatory monocytes and M2 polarized macrophages are enriched and overexpress CCL20•Disruption of the CCL20/CCR6 axes relieves T cell exhaustion and extends survival
Kfoury et al. identify an immune-suppressive microenvironment in human bone metastatic prostate cancer enriched in exhausted T cells and orchestrated by myeloid cells overexpressing CCL20. Pharmacological or genetic targeting of the CCL20/CCR6 axes in an animal model relieves the immune-suppressive state and extends the survival of metastatic tumor-bearing mice.
The book covers the history of plastic surgery from the remarkable achievements of ancient civilizations e.g. India and Egypt, through the classical times of ancient Greece and Rome, up to the ...revolutionary techniques developed at the end of the Middle Age, the Renaissance and then beyond. Surgical progress has usually relied on the parallel development of anatomy. The knowledge of wound healing and how this has changed and influenced plastic surgery is covered in the first part. The development of the basic techniques of the specialty such as skin flaps, the grafting of skin and other tissues are followed throughout the centuries. In the Second Part the development of various surgical reconstructive procedures are described. The reader will realize how techniques which are routine today have evolved thanks to the ingenuity of our surgical ancestors. Finally in Part Three the birth of Cosmetic Surgery, which has fulfilled the dreams of our ancestors, is outlined. Its rapid development is described stressing the efforts required to overcome the prejudices and criticism.
The high mortalities observed during Octopus vulgaris paralarvae culture have been associated with a nutritional imbalance, with long-chain polyunsaturated fatty acids (LC-PUFA) appearing to have a ...critical role. In order to determine the in vivo capability of O. vulgaris hatchlings to incorporate and metabolise unsaturated fatty acids (FA), hatchlings were incubated in flat-bottom 6-well tissue culture plates at a density of 90 hatchlings/well in 10mL of seawater (36‰). Incubations were performed with gentle stirring at 21°C for 6h with 0.2μCi (0.3μM) of 1−14C-labelled FA including 18:1n−9, 18:2n−6, 18:3n−3, 20:4n−6 (ARA), 20:5n−3 (EPA) or 22:6n−3 (DHA), which were added directly to the seawater as their potassium salts bound to bovine serum albumin (BSA). A control treatment without 1−14CFA was also assessed. O. vulgaris hatchlings not only possessed the ability to incorporate FA bound to BSA, but also to esterify them into phospholipid, with marked specificity. 1−14CDHA and 1−14CC18 FA substrates were mainly esterified into phosphatidylcholine, while 1−14CARA and 1−14CEPA were esterified into phosphatidylethanolamine. The majority of radioactivity from 1−14CFA incorporated into hatchling total lipid was recovered as unmodified FA with elongation being the only metabolism detected. Of the FA investigated, 1−14CARA was the most efficiently incorporated into hatchling lipids, but it was also the least modified FA. The fact that no desaturation activity was recorded towards the FA tested in this experiment may indicate that the nutritional requirements of O. vulgaris hatchlings in terms of FA are highly specific and LC-PUFA must be considered essential dietary nutrients.
•Hatchlings presented the capacity to incorporate 1−14C-labelled FA bound to BSA.•1−14C ARA was the most efficiently incorporated and the least modified FA.•Incorporated FA were specially esterified into phospholipids with marked specificity.•The majority of radioactivity incorporated was recovered as unmodified FA.•Only elongations of 1−14C FA substrates were observed.
The treatment of low-risk primary prostate cancer entails active surveillance only, while high-risk disease requires multimodal treatment including surgery, radiation therapy, and hormonal therapy. ...Recurrence and development of metastatic disease remains a clinical problem, without a clear understanding of what drives immune escape and tumor progression. Here, we comprehensively describe the tumor microenvironment of localized prostate cancer in comparison with adjacent normal samples and healthy controls. Single-cell RNA sequencing and high-resolution spatial transcriptomic analyses reveal tumor context dependent changes in gene expression. Our data indicate that an immune suppressive tumor microenvironment associates with suppressive myeloid populations and exhausted T-cells, in addition to high stromal angiogenic activity. We infer cell-to-cell relationships from high throughput ligand-receptor interaction measurements within undissociated tissue sections. Our work thus provides a highly detailed and comprehensive resource of the prostate tumor microenvironment as well as tumor-stromal cell interactions.
We report the final results of the search for gravitationally lensed flat-spectrum radio sources found in the combination of CLASS (Cosmic Lens All-Sky Survey) and JVAS (Jodrell Bank VLA Astrometric ...Survey). VLA (Very Large Array) observations of 16 503 sources have been made, resulting in the largest sample of arcsec-scale lens systems available. Contained within the 16 503 sources is a complete sample of 11 685 sources which have two-point spectral indices between 1.4 and 5 GHz flatter than −0.5, and 5-GHz flux densities ⩾30 mJy. A subset of 8958 sources form a well-defined statistical sample suitable for analysis of the lens statistics. We describe the systematic process by which 149 candidate lensed sources were picked from the statistical sample on the basis of possessing multiple compact components in the 0.2-arcsec resolution VLA maps. Candidates were followed up with 0.05-arcsec resolution MERLIN and 0.003-arcsec VLBA observations at 5 GHz and rejected as lens systems if they failed well-defined surface brightness and/or morphological tests. To illustrate the candidate elimination process, we show examples of sources representative of particular morphologies that have been ruled out by the follow-up observations. 194 additional candidates, not in the well-defined sample, were also followed up. Maps for all the candidates can be found on the World Wide Web at http://www.jb.man.ac.uk/research/gravlens/index.html. We summarize the properties of each of the 22 gravitational lens systems in JVAS/CLASS. 12 are double-image systems, nine are four-image systems and one is a six-image system. 13 constitute a statistically well-defined sample giving a point-source lensing rate of 1:690 ± 190. The interpretation of the results in terms of the properties of the lensing galaxy population and cosmological parameters will be published elsewhere.
In this study, two new alternative preys: Grapsus adscensionis zoeae (as sole prey) and Palaemon elegans zoeae (in cofeeding with Artemia sp.), as well as, Artemia sp. juveniles were used as feed for ...octopus paralarvae, as a way to understand its lipid requirements. Total lipid (TL) content, lipid class (LC) and fatty acid (FA) profiles of preys, octopus hatchlings and 9‐day‐old paralarvae were analysed. Growth and survival of the paralarvae were also determined. Regardless the prey provided, a notable shift in the lipid profile of paralarvae was registered after 9 days of rearing. The highest index of growth rate (IGR) recorded when decapod crustacean zoeae were supplied might have some relation with levels of 20:4n‐6 (ARA) and DHA/EPA ratio observed. In this sense, Grapsus adscensionis zoeae leaded to a higher content of ARA and a lower content of EPA, which may indicate a possible competition between these two FA. For that a balanced EPA/ARA ratio might be significant in this species nutrition without disconsidering DHA levels as an essential fatty acid. Finally, the changes observed in paralarvae FA profile might not only be related to prey FA profile, but also with changes occurring in the lipid classes contents.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK