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Kelp forests are an important ecological component of temperate coastal systems that are sensitive to anthropogenic disturbance and are in decline in many locations globally. In the northeastern Pacific Ocean off the coast of Washington, USA, bull kelp Nereocystis luetkeana forests are seasonally used by juvenile salmonids and forage fishes; however, details on ecosystem functional linkages for forage fishes and salmonids are not well quantified. Using a zooplankton drop net and snorkel surveys for fishes, we sampled two bull kelp forests across multiple years. Our goal was to quantify differences in the communities of zooplankton, juvenile salmonids (Chinook Salmon Oncorhynchus tshawytscha and Coho Salmon O. kisutch), and forage fishes (Pacific Herring Clupea pallasii, Surf Smelt Hypomesus pretiosus, and Pacific Sand Lance Ammodytes hexapterus) between kelp forests and adjacent nonkelp (open-water) habitats. We tested the hypothesis that zooplankton common in the diets of surfaceoriented forage fishes and juvenile salmonids would be more abundant in kelp than in open water. At the overall assemblage level of organization, kelp and open-water habitats had similarly abundant and diverse zooplankton communities. However, decapods and phytal-associated harpacticoid copepods within this assemblage (i.e., groups that are an important component of fish diets) were significantly more abundant in kelp forests than in open-water habitat. Greater presence and abundance of zooplankton, juvenile salmonids, and forage fishes in kelp forests compared to adjacent open-water habitats suggest that kelp forests are important for culturally and economically valuable forage fishes and salmonids and warrant further study to define and conserve their ecosystem function. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs), which degrade extracellular proteins as part of a variety of physiological processes, and their inhibitors have been implicated in the dental caries process. Here we investigated 28 genetic variants spanning the MMP10, MMP14, and MMP16 genes to detect association with dental caries experience in 13 age- and race-stratified (n=3,587) samples from 6 parent studies. Analyses were performed separately for each sample, and results were combined across samples by meta-analysis. Two SNPs (rs2046315 and rs10429371) upstream of MMP16 were significantly associated with caries in an individual sample of white adults and via meta-analysis across 8 adult samples after gene-wise adjustment for multiple comparisons. Noteworthy is SNP rs2046315 (p=8.14×10-8) association with caries in white adults. This SNP was originally nominated in a genome-wide-association study (GWAS) of dental caries in a sample of white adults and yielded associations in a subsequent GWAS of surface level caries in white adults as well. Therefore, in our study, we were able to recapture the association between rs2046315 and dental caries in white adults. Although we did not strengthen evidence that MMPs 10, 14, and 16 influence caries risk, MMP16 is still a likely candidate gene to pursue. [ABSTRACT FROM AUTHOR]

In addition to the downstream migration of smolts in spring, Coho SalmonOncorhynchus kisutchalso enter estuaries throughout the year but especially in the spring as fry and in the fall as parr. The removal of two large dams on the Elwha River, Washington, has increased the area accessible to salmon and is affecting many aspects of the system. For comparison with the postdam period, when the Elwha River estuary will likely expand in size and complexity, monthly sampling was conducted in the estuary during 2007–2011 to determine patterns of Coho Salmon presence and size prior to dam removal; Salt Creek, a nearby undammed stream, was also sampled to allow comparison of fish size and seasonal timing patterns. The spring smolt migration in the Elwha River included a large fraction of unmarked fish (primarily of natural origin) as well as marked fish from the Lower Elwha Klallam Tribe Fish Hatchery. Subyearlings entered both estuaries during much of the year, exhibiting a peak in September. Coho Salmon from the Elwha River (including wild and hatchery-origin fish) were larger and more heavily represented in the fall relative to the spring smolt migration compared to those from Salt Creek. Future patterns in the Elwha River may include reduced presmolt use of the estuary if the center of distribution is farther upriver, but improved estuarine habitat may make it more suitable for presmolts. Received November 21, 2012; accepted April 3, 2013 [ABSTRACT FROM AUTHOR]

Background Home parenteral nutrition ( HPN) is currently the management of choice for patients with chronic intestinal failure. Aim To summarise the major issues in delivering long-term parenteral nutrition (>3 months) and assess outcome as per complications, mortality and quality of life. To assess the evidence for the therapeutic use of trophic factors such as teduglutide and to review evolving therapeutic options in the treatment of chronic intestinal failure. Methods A literature search using PubMed and MEDLINE databases was performed. Results Safe delivery of HPN relies upon individualised formulations of parenteral nutrition administered via carefully maintained central venous catheters by trained patients or carers, supported by a skilled multidisciplinary team. Early diagnosis and treatment of complications including catheter-associated blood stream infection (reported incidence 0.14-0.83 episodes/patient-year on HPN) and central venous thrombosis (reported incidence 0.03 episodes/patient-year) is important to minimise mortality and morbidity. There is a significant variation in the reported incidence of both hepatobiliary complications (19-75%) and advanced liver disease (0-50%). Five-year survival rates in large centres are reported between 60% and 78% with survival primarily related to underlying diagnosis. Long-term survival remains higher on HPN than with intestinal transplantation. The role of intestinal lengthening procedures is yet to be validated in adults. Conclusions Home parenteral nutrition delivered by skilled nutrition teams has low incidences of catheter-related complications. Most deaths relate to the underlying disease. Therapies such as teduglutide and small bowel transplantation appear promising, but home parenteral nutrition appears likely to remain the bedrock of management in the near term. [ABSTRACT FROM AUTHOR]

Background: Perioperative oral supplementation has been shown to reduce post-operative complications. However, the use of preoperative standard oral supplements in a cohort of colorectal cancer patients has not been evaluated. The present study examined whether preoperative supplements are beneficial in this group. Methods: In a randomised controlled trial, patients were assigned to receive 400 mL of oral supplement and dietary advice or dietary advice alone. Primary outcome was the number of post-operative complications. One hundred and twenty-five patients were recruited (59 randomised to the intervention group and 66 to the control group) and nine were excluded. Results: In the intervention group, 24 (44%) patients had a complication compared to 26 (42%) in the control group ( P = 0.780). In the intervention and control groups, there were eight (15%) and 16 (25%) surgical site infections, respectively ( P = 0.140) and seven (13%) and 11 (17%) chest infections, respectively ( P = 0.470). Subgroup analysis for hypothesis generation included 83 (71%) weight-losing patients, where there was a significant reduction in surgical site infections using the Buzby definition ( P = 0.034), although this was not the case for the Centre for Disease Control definition ( P = 0.052). Conclusions: There was no evidence that preoperative supplements were beneficial in reducing the number of complications, although there may be some benefit for surgical site infections in selected weight-losing preoperative patients. [ABSTRACT FROM AUTHOR]

Background: The present study aimed to determine the extent of malnutrition in preoperative colorectal cancer patients. Malnutrition has been shown to affect post-operative outcome, so it would be beneficial to identify those who are malnourished or who are at risk of becoming so preoperatively. We examine whether weight loss is related to the length of stay or changes in fat free mass. Methods: Patients were enrolled consecutively from outpatients 2–4 weeks prior to surgery. Assessments included body mass index, percentage weight loss, dynamometry, Malnutrition Universal Screening Tool, Subjective Global Assessment and bioelectrical impedance. Cancer staging and hospital length of stay were recorded. Results: One hundred and thirty-two patients were eligible and 87 enrolled. Sixty-seven patients were weight losing and 20% had lost >10% of their usual body weight. Handgrip strength was lower in malnourished patients compared to those who had not lost weight (mean 19.4 and 27.3 kg, respectively, P = 0.013). Mean (SD) fat free mass in patients with a weight loss >10% was 39.7 (13.5) kg and, in those with <10% weight loss, was 51.9 (12.0) kg ( P = 0.001). This difference was not demonstrated for fat. Conclusions: Over half of these patients had lost weight prior to surgery and one in five were malnourished. Body composition measurements demonstrated that malnourished patients had significantly less fat free mass compared to patients who were not clinically malnourished. Nutritional screening would be beneficial in this group preoperatively to identify weight-losing patients at an early stage in the care pathway when they initially enter the secondary care system. [ABSTRACT FROM AUTHOR]

Introduction: Although the association between depression and cardiovascular disease (CVD) is well documented, the underlying mechanisms for this relationship remain unclear. In this paper, we present three possible models which account for the comorbidity between depression and cardiovascular disease. Models: The first model outlines depression as a risk factor for CVD and the second model presents CVD as a risk factor for depression. The third model proposes a common underlying pathway related to the effects of chronic stress on the body in manifesting as depression or cardiovascular disease. Conclusions: If the proposed model holds true, it may be possible that an intervention initiated before overt manifestations of CVD or depression become apparent, may delay or prevent the onset of these serious clinical entities. [ABSTRACT FROM AUTHOR]

Background: Azathioprine is an immunosuppressant prescribed for the treatment of inflammatory conditions and after organ transplantation. Risk of neutropaenia has limited the effective use of azathioprine (AZA) and driven requirements for careful monitoring and blood tests. Thiopurine methyltransferase (TPMT) is a genetically moderated key enzyme involved in the metabolism of AZA that can be used to stratify individuals into different levels of risk of developing neutropaenia. Two techniques can be used to measure TPMT status: enzyme-level testing (phenotype testing) and DNA based testing (genotype testing). Objective: To identify the current uptake of TPMT enzyme-level testing, TPMT genotype testing, and, the role of guidelines; to inform the prescribing and monitoring of AZA. Method: A survey was mailed to a consultant dermatologist, gastroenterologist, and rheumatologist at every NHS Hospital Trust in England. The survey comprised mainly closed questions exploring: use of AZA and monitoring; use of TPMT enzyme-level testing and genotype testing; and, the role of guidelines to guide prescribing practice. Results: A 70% ( n = 287) response rate was obtained. The majority of respondents reported prescribing AZA (99%, n = 283). Prescribing and monitoring patterns differed between individual respondents and between the three disciplines. TPMT enzyme-level testing was reportedly used by 67% ( n = 189) of respondents, but this differed by discipline (dermatologists 94%, gastroenterologists 60%, rheumatologists 47%). In 91% of cases enzyme-level testing was carried out prior to prescribing AZA. Genotype testing is not typically available to NHS clinicians but 15 clinicians (six dermatologists, six gastroenterologists, three rheumatologists) reported using it. Most consultants (82%) reported using guidelines to inform their AZA prescribing and monitoring (dermatologists 81%, gastroenterologists 75%, rheumatologists 94%). Conclusion: Two-thirds of the consultants surveyed in England are using TPMT enzyme-level testing, prior to AZA treatment. Uptake differs between specialities. High uptake of TPMT enzyme-level testing by dermatologists, compared with gastroenterologists and rheumatologists, may reflect national guidelines advocating its use prior to AZA. Uptake of enzyme-level testing may alter in other specialties as other guidelines are developed. [ABSTRACT FROM AUTHOR]

Intestinal failure is a specific disease entity resulting from intestinal resection or disease-associated malabsorption and characterized by the inability to maintain protein-energy, fluid, electrolyte or micronutrient balance. We performed a MEDLINE search (1966–2006) to identify relevant articles, using keywords intestinal failure, parenteral or enteral nutrition, intestinal fistula and short bowel syndrome. Causes of intestinal failure are varied, with self-limiting or ‘Type 1’ intestinal failure occurring relatively commonly following abdominal surgery, necessitating short-term fluid or nutritional support. The rarer, ‘Type 2’ intestinal failure, is associated with septic, metabolic and complex nutritional complications, usually following surgical resection in patients with Crohn's or mesenteric vascular disease. A multidisciplinary approach to the management of patients with Type 2 intestinal failure is crucial: resolution of sepsis is required before adequate nutritional repletion can be achieved, and it is important to optimize nutritional status, not only through enteral or parenteral supplementation, but also by addressing complications of short bowel syndrome, before considering definitive surgical reconstruction. A structured approach to the management of Type 2 intestinal failure should reduce the likelihood of these complex patients developing ‘Type 3’ intestinal failure, which is characterized by the need for long-term parenteral nutrition. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIMS: Mid upper arm anthropometry (MUAA) is often used as a measure of nutritional status to detect changes in body composition. The aim of this study was to investigate the reliability and validity of MUAA including mid arm circumference (MAC) and triceps skin fold thickness (TSFT) to determine the usefulness in clinical practice. METHOD: We measured MUAA in 158 consecutive admissions along with subjective global assessment (SGA) and body mass index (BMI). Inter- and intra-rater reliability was evaluated in an additional 50 patients. RESULTS: The sensitivity and specificity of MUAA <5th percentile was compared with SGA and BMI. MAC and TSFT had a low sensitivity and a high specificity with low positive predictive values when compared with criterion values which were BMI

In the yellow fever mosquitoAedes aegypti, theferritin heavy-chain homologue(HCH) gene is induced by blood feeding. This suggests that ferritin may serve as a cytotoxic protector against the oxidative challenge of the blood meal and may be essential for the survival of the insect. In this study, variouscis-acting elements for the gene were identified and mapped. Transfection assays showed that the strength and activity of a subset of these elements are orientation-dependent. The shift observed for theferritin HCH cis-acting elements is unique among knownferritingenes. DNase I footprinting data together withTransfacanalyses identified a number of putative sites known for their involvement in developmental and cell proliferation processes. [ABSTRACT FROM AUTHOR]

Blood concentrations of promethazine and promethazine sulphoxide have been measured following oral and intravenous administration of promethazine to seven healthy male volunteers. Promethazine disposition is characterised by a large volume of distribution (1970 1) and a high blood clearance (1.141 min-1). Less than 1% of the dose is excreted unchanged in the urine, therefore total body clearance is essentially metabolic clearance. In accord with this high clearance the oral availability of promethazine is only 25%. The absorption of promethazine from the gastrointestinal tract exceeds 80% in most subjects. Minimal metabolism by the gastrointestinal mucosa is implicated. Promethazine sulphoxide pharmacokinetics are consistent with a pronounced first pass effect. Although the area under the curve for this metabolite is not route dependent, there is a marked alteration in the shape of the metabolite curve when oral and intravenous data are compared. Evidence is presented to support the hypothesis that S-oxidation of promethazine is predominantly an hepatic event. The conclusions of previous investigators with regard to the role of the gut mucosa in S-oxidation of phenothiazines is critically assessed. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is becoming prevalent in Africa, where malaria is endemic. Observational studies have documented the long-term protective effect of malaria on dyslipidemia; however, these study designs are prone to confounding. Therefore, we used Mendelian randomization (MR, a method robust to confounders and reverse causation) to determine the causal effect of severe malaria (SM) and the recurrence of non-severe malaria (RNM) on lipid traits., Method: We performed two-sample MR using genome wide association study (GWAS) summary statistics for recurrent non-severe malaria (RNM) from a Benin cohort (N = 775) and severe malaria from the MalariaGEN dataset (N = 17,000) and lipid traits from summary-level data of a meta-analyzed African lipid GWAS (MALG, N = 24,215) from the African Partnership for Chronic Disease Research (APCDR) (N = 13,612) and the Africa Wits-IN-DEPTH partnership for genomics studies (AWI-Gen) dataset (N = 10,603)., Result: No evidence of significant causal association was obtained between RNM and high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglycerides. However, a notable association emerged between severe malarial anaemia (SMA) which is a subtype of severe malaria and reduced HDL-C levels, suggesting a potential subtype-specific effect. Nonetheless, we strongly believe that the small sample size likely affects our estimates, warranting cautious interpretation of these results., Conclusion: Our findings challenge the hypothesis of a broad causal relationship between malaria (both severe and recurrent non-severe forms) and dyslipidemia. The isolated association with SMA highlights an intriguing area for future research. However, we believe that conducting larger studies to investigate the connection between malaria and dyslipidemia in Africa will enhance our ability to better address the burden posed by both diseases., (© 2024 The Authors. Annals of Human Genetics published by University College London (UCL) and John Wiley & Sons Ltd.)

Based on a murine model, we conducted a series of trials of m-myeloablative human leucocyte antigen (HLA)-matched or mismatched related donor stem cell transplantation (SCT) with the intention of inducing mixed chimaerism (MC), then administering prophylactic donor lymphocyte infusions (DLIs), for the treatment of advanced haematologic malignancies. Preparative therapy consisted of cyclophosphamide, equine anti-thymocyte globulin (ATG) or MEDI-507 (an anti-CD2 monoclonal antibody) for in-vivo T-cell depletion, thymic irradiation on day -1 and cyclosporine alone for graft-versus-host disease (GVHD) prophylaxis. DLIs were given as early as 5 weeks post-SCT in patients with MC without evidence of GVHD. Twenty-two patients ultimately lost their graft (<1% donor cells) that could no be rescued by DLIs. Nine of 22 (41%) patients who lost donor chimaerism achieved an objective response, including three patients who showed evidence of disease regression following DLI, despite continued absence of macrochimaerism. Six patients were alive at 2.5-5.5 years following SCT, including four in continuous complete remission. In summary, it is possible to achieve sustained remission in patients with chemorefractory malignancies following non-myeloablative allogeneic SCT, even in the absence of sustained donor macrochimaerism; DLI may contribute to an ongoing anti-tumour effect in these patients. Immunological mechanisms that correlated with rejection of the graft may have a role in anti-tumour responses via a cell or cytokine-mediated pathway.

Malnutrition is common and undiagnosed in the majority of affected hospital patients; it is associated with impaired organ function, morbidity, and increased length of hospital stay. Artificial nutritional support in malnourished patients leads to improvement in nutritional status and clinical outcome. Nutritional support is required in malnourished patients, patients who are unable to take normal diet and patients with intestinal failure. Gastroenterologists are required to supervise patients with intestinal failure, to insert endoscopic feeding devices, and increasingly to participate in, or lead, nutritional support teams. Major developments in nutrient delivery have included percutaneous endoscopic feeding devices, the recognition that enteral feeding is possible in patients with gastric stasis, and that nutrient needs can be met by peripheral parenteral nutrition. There is much interest in the use of new substrates, or substrates delivered in pharmacological doses such as glutamine and arginine, to manipulate the response to disease. Many hospitals lack an organized approach to artificial nutritional support. Patients continue to suffer from a lack of treatment or the consequences of inappropriate or inadequate treatment. This article reviews the current status of artificial nutritional support and provides guidelines for patient management.

The pharmacokinetics of metronidazole were studied after oral and intravenous administration to seven patients with Crohn's disease and five patients with ulcerative colitis. The oral/intravenous availability ratio was 0.97 +/- 0.2 in the Crohn's patients and 0.90 +/- 0.1 in the colitics (mean +/- s.e. mean). Plasma clearance was 3.24 +/- 0.2 l h-1 and 4.1 +/- 0.5 l h-1, respectively. These differences were not statistically significant. Ten of the patients on long term sulphasalazine were studied to observe the effect of 2 weeks metronidazole therapy on plasma sulphapyridine concentration. The sulphapyridine concentration changed from 22.1 +/- 2.0 micrograms ml-1 to 15.95 +/- 4.5 micrograms ml-1 in the Crohn's patients and 26.0 +/- 6.0 micrograms ml-1 to 36.4 +/- 8.5 micrograms ml-1 in the colitis group, pre- and post-metronidazole. These differences were not statistically significant. These results suggest that metronidazole does not interfere with diazo-link splitting of sulphasalazine and that patients with Crohn's disease handle metronidazole in a similar manner to patients with colitis.