Kelp detritus: Unutilized productivity or an unacknowledged trophic resource?

Kelp beds are one of the most productive marine systems and, while little of this production is directly consumed, there is growing evidence that kelp detritus is an essential food source for many detrital and suspension feeders, and forms an important component of offshore sedimentary carbon pools. However, the extent of the contribution of kelp detritus to the nutrition of coastal fauna is not well resolved. In this study, we compare the contribution of phytoplankton, kelp detritus, and waste from fish cages to the diet of a sentinel suspension feeder, the blue mussel (Mytilus edulis) using stable isotopes. We found a significant depletion in both 13C and 15N in kelp tissue with age (distance from stipe to the deteriorating distal end of the kelp frond) which may have biased dietary estimates in previous studies which have applied isotopic source values derived from fresh kelp. Our mixing models indicate that macroalgal detritus formed 59% of the diet of the mussels in Berehaven, Bantry Bay, Ireland. We support the isotopic mixing model results by modelling the relative production of phytoplankton, kelp, and salmon farm waste, and found the supply of C and N from kelp and phytoplankton far exceeded the requirements of the mussels with much less coming from the nearby fish cages. Monthly chlorophyll measurements indicated there was only sufficient phytoplankton density to support mussel growth during the spring and autumn, explaining our observation of patterns in the relative importance of utilization of kelp detritus. Where there is pressure to harvest kelp beds, this study highlights the supporting ecosystem service they provide as an important dietary source in coastal food webs and emphasises the need for appropriate management measures for this resource.

Candida Endocarditis: A Review of the Pathogenesis, Morphology, Risk Factors, and Management of an Emerging and Serious Condition.

Infective endocarditis is a significant healthcare burden due to the associated high mortality and complications. Endocarditis caused by both Candida albicans (C. albicans) and non-Candida albicans Candida (NCAC) species has been associated with a substantial rise in in-hospital morbidity and mortality. We used the Pubmed database to identify 47 out of 101 articles that had met our inclusion and exclusion criteria. We had put in place a broad inclusion criterion with no age or gender restrictions. These 47 articles included abstracts, 11 review articles, 13 case reports, 10 research articles, 1 clinical trial report, 1 meta-analysis, and other research articles. And they comprehensively cover the pathogenesis, risk factors, and management of infections caused by C. albicans and NCAC species in the past 26 years. The articles we scanned provided us with information on different associations in correlation to multiple types of Candida species. Here, we discuss the association between Candida and endocarditis, a major cause of morbidity and mortality in both C. albicans and NCAC. We also present our understanding regarding this interesting association and attempt to address some of the recurring questions.

Association Between Cerebrovascular Accident and Vasculitis: Myth or Reality?

This article aims to determine an association between vasculitis and cerebrovascular accidents (CVA) and the ideal management plan to decrease the chances of CVA in vasculitis patients. We also attempt to find a preferred treatment regimen that decreases the complications of CVAs in vasculitis patients, thereby resulting in reduced mortality and morbidity. We reviewed both free-access full-text articles and the abstracts of articles behind a paywall. We used the PubMed database and reviewed 89 articles that matched our inclusion and exclusion criteria. In all, 42 out of the 89 articles had the most relevant data for our article. We used the following keywords to search the database: vasculitis, stroke, cerebrovascular accident, ischemic, arteritis, and steroid. We found an association between subtypes of vasculitis, mostly large vessel vasculitis and CVA. We could not identify a specific cutoff value for specific inflammatory markers that can increase the risk of developing CVA. Besides, there are no formal guidelines for the dosage or the route of administration for corticosteroids, which are the cornerstone of treatment for most vasculitis. We found that male giant cell arteritis (GCA) patients have a higher chance of developing CVA than females, Also interestingly, anemia was found to be protective against CVA development in GCA patients. Sometimes, CVA can happen due to the effects of treatments of some types of vasculitis. We recommend establishing further studies about other subtypes of vasculitis and their associations with stroke.

Impact of peer support on inpatient and outpatient payments among people with Type 2 diabetes: a prospective cohort study.

AIM: To investigate the impact of a low-cost diabetes peer-support intervention, aimed at reducing inpatient and outpatient care utilization and healthcare payments, by conducting a cohort study that followed up a randomized controlled trial. METHODS: A total of 1121 adults with Type 2 diabetes were recruited through general practices in Cambridgeshire and Hertfordshire, UK, and were followed up for 3.25 financial years after 8-12 months of one-to-one, group or combined diabetes peer support and usual care. Use of, and payments for inpatient and outpatient services were fully recorded in the follow-up. Adjusted mean inpatient and outpatient payments per person were estimated using a two-part model after adjusting for baseline characteristics. RESULTS: The mean age of the recruited adults was 65.6±11.4 years, 60.4% were male, and 16.8% were insulin-treated. Compared with the control group, less healthcare utilization (especially non-elective inpatient care and outpatient consultations) was observed in each of the intervention groups, particularly the combined intervention group. Over the course of 3.25 financial years, significant reductions of 41% (£909.20 per head) were observed for overall inpatient payments (P<0.0001), 51% (£514.67 per head) for non-elective inpatient payments (P=0.005) in the combined intervention group, and 34% (£413.30 per head) and 32% (£388.99 per head) for elective inpatient payments in the one-to-one (P=0.029) and combined intervention (P=0.048) groups, respectively. CONCLUSIONS: Type 2 diabetes peer support, whether delivered using a one-to-one, group or combined approach was associated with reduced inpatient care utilization (particularly non-elective admissions) and payments over 3.25 years.

SMi'S 4th Annual Orphan Drugs and Rare Diseases Conference (October 19-20, 2015--London, UK).

The story of rare diseases is a story of people. Often very young, and usually with little hope of treatment, it is often a desperately sad and tragic story, but increasingly a story of hope. Statistics are inescapable when discussing the subject: small numbers of patients in huge populations, the massively disproportionate contribution to pediatric mortality, and the necessarily high prices for rare drugs. Almost every speaker at the SMi's Fourth Orphan Drugs and Rare Diseases conference provided figures that illustrated just how different this area is to the macro-world of the blockbuster drug.

Mitigation assessment of vegetated drainage ditches for collecting irrigation runoff in California.

Widespread contamination of California water bodies by the organophosphate insecticides diazinon and chlorpyrifos is well documented. While their usage has decreased over the last few years, a concomitant increase in pyrethroid usage (e.g., permethrin) (replacement insecticides) has occurred. Vegetated agricultural drainage ditches (VADD) have been proposed as a potential economical and environmentally efficient management practice to mitigate the effects of pesticides in irrigation and storm runoff. Three ditches were constructed in Yolo County, California for a field trial. A U-shaped vegetated ditch, a V-shaped vegetated ditch, and a V-shaped unvegetated ditch were each amended for 8 h with a mixture of diazinon, permethrin, and suspended sediment simulating an irrigation runoff event. Water, sediment, and plant samples were collected spatially and temporally and analyzed for diazinon and permethrin concentrations. Pesticide half-lives were similar between ditches and pesticides, ranging from 2.4 to 6.4 h. Differences in half-distances (distance required to reduce initial pesticide concentration by 50%) among pesticides and ditches were present, indicating importance of vegetation in mitigation. Cis-permethrin half-distances in V ditches ranged from 22 m (V-vegetated) to 50 m (V-unvegetated). Half-distances for trans-permethrin were similar, ranging from 21 m (V-vegetated) to 55 m (V-unvegetated). Diazinon half-distances demonstrated the greatest differences (55 m for V-vegetated and 158 m for V-unvegetated). Such economical and environmentally successful management practices will offer farmers, ranchers, and landowners a viable alternative to more conventional (and sometimes expensive) practices.

Oxygen free radical damage to DNA. Translesion synthesis by human DNA polymerase eta and resistance to exonuclease action at cyclopurine deoxynucleoside residues.

Cyclopurine deoxynucleosides are common DNA lesions generated by exposure to reactive oxygen species under hypoxic conditions. The S and R diastereoisomers of cyclodeoxyadenosine on DNA were investigated separately for their ability to block 3' to 5' exonucleases. The mammalian DNA-editing enzyme DNase III (TREX1) was blocked by both diastereoisomers, whereas only the S diastereoisomer was highly efficient in preventing digestion by the exonuclease function of T4 DNA polymerase. Digestion in both cases was frequently blocked one residue before the modified base. Oligodeoxyribonucleotides containing a cyclodeoxyadenosine residue were further employed as templates for synthesis by human DNA polymerase eta (pol eta). pol eta could catalyze translesion synthesis on the R diastereoisomer of cyclodeoxyadenosine. On the S diastereoisomer, pol eta could catalyze the incorporation of one nucleotide opposite the lesion but could not continue elongation. Although pol eta preferentially incorporated dAMP opposite the R diastereoisomer, elongation continued only when dTMP was incorporated, suggesting bypass of this lesion by pol eta with reasonable fidelity. With the S diastereoisomer, pol eta mainly incorporated dAMP or dTMP opposite the lesion but could not elongate even after incorporating a correct nucleotide. These data suggest that the S diastereoisomer may be a more cytotoxic DNA lesion than the R diastereoisomer.

Excision of deaminated cytosine from the vertebrate genome: role of the SMUG1 uracil-DNA glycosylase.

Gene-targeted mice deficient in the evolutionarily conserved uracil-DNA glycosylase encoded by the UNG gene surprisingly lack the mutator phenotype characteristic of bacterial and yeast ung(-) mutants. A complementary uracil-DNA glycosylase activity detected in ung(-/-) murine cells and tissues may be responsible for the repair of deaminated cytosine residues in vivo. Here, specific neutralizing antibodies were used to identify the SMUG1 enzyme as the major uracil-DNA glycosylase in UNG-deficient mice. SMUG1 is present at similar levels in cell nuclei of non-proliferating and proliferating tissues, indicating a replication- independent role in DNA repair. The SMUG1 enzyme is found in vertebrates and insects, whereas it is absent in nematodes, plants and fungi. We propose a model in which SMUG1 has evolved in higher eukaryotes as an anti-mutator distinct from the UNG enzyme, the latter being largely localized to replication foci in mammalian cells to counteract de novo dUMP incorporation into DNA.

Voxel significance mapping using local image variances in subtraction ictal SPET.

Subtraction ictal SPET co-registered to MRI (SISCOM) has been shown to aid epileptogenic localization and improve surgical outcome in partial epilepsy patients. This paper reports a method of identifying significant areas of epileptogenic activation in the SISCOM subtraction image, taking into account normal variation between sequential 99Tcm-ethyl cysteinate diethylester SPET scans of single individuals, and attempts to assess the clinical value of statistical mapping in subtraction SPET. Non-linear inter-subject registration is used to combine a group of subtraction images into a common anatomical framework. A map of the pixel intensity standard deviation values in the subtraction images is created, and this map is non-linearly registered to a patient's SISCOM subtraction image. Pixels in the patient subtraction image were then evaluated based upon the statistical characteristics of corresponding pixels in the atlas. SISCOM images created with the voxel variance method were rated higher in quality than the conventional image variance method in 15 patients. No difference in localization rate was observed between the voxel variance mapping and image variance methods. The voxel significance mapping method was shown to improve the quality of clinical SISCOM images.

Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme during DNA replication.

Gene-targeted knockout mice have been generated lacking the major uracil-DNA glycosylase, UNG. In contrast to ung- mutants of bacteria and yeast, such mice do not exhibit a greatly increased spontaneous mutation frequency. However, there is only slow removal of uracil from misincorporated dUMP in isolated ung-/- nuclei and an elevated steady-state level of uracil in DNA in dividing ung-/- cells. A backup uracil-excising activity in tissue extracts from ung null mice, with properties indistinguishable from the mammalian SMUG1 DNA glycosylase, may account for the repair of premutagenic U:G mispairs resulting from cytosine deamination in vivo. The nuclear UNG protein has apparently evolved a specialized role in mammalian cells counteracting U:A base pairs formed by use of dUTP during DNA synthesis.

Biodistribution and radiation dosimetry of stabilized 99mTc-exametazine-labeled leukocytes in normal subjects.

UNLABELLED: Labeling leukocytes with 99mTc-exametazime is a validated technique for imaging infection and inflammation. A new radiolabeling technique has recently been described that enables leukocyte labeling with a more stable form of 99mTc-exametazime. A normal value study of stabilized 99mTc-exametazime-labeled leukocytes has been performed, including biodistribution and dosimetry estimates in normal subjects. METHODS: Ten volunteers were injected with stabilized 99mTc-exametazime-labeled autologous leukocytes to study labeled leukocyte kinetics and dosimetry in normal subjects. Serial whole-body imaging and blood sampling were performed up to 24 h after injection. Cell-labeling efficiency and in vivo viability, organ dosimetry, and clearance calculations were obtained from the blood samples and imaging data as well as urine and stool collection up to 36 h after injection. RESULTS: Cell-labeling efficiency of 87.5% +/- 5.1% was achieved, which is similar to or better than that reported with the standard preparation of 99mTc-exametazime. In vivo stability of the radiolabeled leukocytes was also similar to in vitro results with stabilized 99mTc-exametazime and better than previously reported in vivo stability for nonstabilized 99mTc-exametazime-labeled leukocytes. Organ dosimetry and radiation absorbed doses were similar with a whole-body absorbed dose of 1.3 x 10(-3) mGy/ MBq. Urinary and fecal excretion of activity was minimal, and visual assessment of the images showed little renal parenchymal activity and no bowel activity up to 2 h after injection. CONCLUSION: Cell labeling and in vivo stability appear improved compared with the leukocytes labeled with the nonstabilized preparation of 99mTc-exametazime. There are advantages in more cost-effective preparation of the stabilized 99mTc-exametazime and an extended window for clinical usage, with good visualization of abdominal structures on early images. No significant increase in specific organ and whole-body dosimetry estimates was noted compared with previous estimates using nonstabilized 99mTc-exametazime-labeled leukocytes.

Biliary sepsis as a cause of appearance of endoluminal Tc-99m HMPAO-labeled leukocytes: a case report.

A case is presented that shows the abnormal early appearance of Tc-99m HMPAO-labeled leukocytes within the small bowel lumen as a result of septic cholangitis. It is essential to perform early images with Tc-99m HMPAO-labeled leukocytes to differentiate between the appearance of abnormal uptake in the bowel and normal physiologic excretion, which occurs later in the renal and biliary tracts. Endoluminal radiolabeled leukocytes have been described in several clinical settings unrelated to bowel disease, such as swallowed activity from sinus or pulmonary infection, and it is important to differentiate this from primary gastrointestinal disease. To our knowledge, acute pyogenic cholangitis has not been shown previously as a cause of these appearances and should be included in the differential diagnosis for the early appearance of mobile radiolabeled leukocytes in the lumen of the gastrointestinal tract.

Clinical experience with radiolabelled monoclonal antibodies in the detection of colorectal and ovarian carcinoma recurrence and review of the literature.

A retrospective study was carried out to determine the diagnostic value of OncoScint CR/OV immunoscintigraphy in assessing patients with suspected recurrence of carcinoma of the colon and ovary. The scintigraphic results of 31 patients were compared with surgical and histopathological findings, conventional radiological examinations and clinical disease outcome over an average 3-year follow-up. Detected lesions were divided by location into hepatic or extrahepatic and the latter group was classified as local recurrence at the resection site, pelvic or abdominal regional lymph node involvement and distant metastatic disease. The combined sensitivity and accuracy of immunoscintigraphy in the detection of extra-hepatic disease was significantly higher than that of cross-sectional radiological imaging (87% and 83% vs 44% and 53% respectively) with equal specificity of 74%. Scintigraphy identified 14 (36%) of 39 extra-hepatic malignant lesions not diagnosed by conventional radiological techniques and influenced therapeutic planning in 8 (26%) of 31 patients studied. In the liver, conventional imaging had a significantly higher detection rate than immunoscintigraphy (sensitivity 93% vs 28%). In conclusion, these results show that OncoScint scintigraphy is a sensitive method for the detection of local recurrence and extra-hepatic metastases in colorectal and ovarian carcinoma and has an important role in the therapeutic decision-making process.