A multiproducer microbiome generates chemical diversity in the marine sponge Mycale hentscheli.

Bacterial specialized metabolites are increasingly recognized as important factors in animal-microbiome interactions: for example, by providing the host with chemical defenses. Even in chemically rich animals, such compounds have been found to originate from individual members of more diverse microbiomes. Here, we identified a remarkable case of a moderately complex microbiome in the sponge host Mycale hentscheli in which multiple symbionts jointly generate chemical diversity. In addition to bacterial pathways for three distinct polyketide families comprising microtubule-inhibiting peloruside drug candidates, mycalamide-type contact poisons, and the eukaryotic translation-inhibiting pateamines, we identified extensive biosynthetic potential distributed among a broad phylogenetic range of bacteria. Biochemical data on one of the orphan pathways suggest a previously unknown member of the rare polytheonamide-type cytotoxin family as its product. Other than supporting a scenario of cooperative symbiosis based on bacterial metabolites, the data provide a rationale for the chemical variability of M. hentscheli and could pave the way toward biotechnological peloruside production. Most bacterial lineages in the compositionally unusual sponge microbiome were not known to synthesize bioactive metabolites, supporting the concept that microbial dark matter harbors diverse producer taxa with as yet unrecognized drug discovery potential.

Intensive Lifestyle Intervention for Obesity: Principles, Practices, and Results.

Using the Guidelines for the Management of Overweight and Obesity in Adults as a framework, this article reviews intensive lifestyle interventions for weight loss. The Guidelines recommend a minimum of 6 months of high-intensity, comprehensive lifestyle intervention, consisting of a reduced-calorie diet, increased physical activity, and behavior therapy. Persons with obesity typically lose approximately 8 kg (approximately 8% of initial weight) with this approach, accompanied by improvements in health and quality of life. To prevent weight regain, the Guidelines recommend a 1-year weight loss maintenance program that includes at least monthly counseling with a trained interventionist. Lifestyle interventions usually are delivered in-person; however, treatment increasingly is being disseminated through community- and commercial-based programs, as well as delivered by telephone, Internet, and smartphone platforms. These latter modalities expand treatment reach but usually produce smaller weight losses than in-person interventions. The review concludes with an examination of challenges in weight management.

In vivo innate immune responses of groper (Polyprion oxygeneios) against Miamiensis avidus infection and lack of protection following dietary vitamin C administration.

Scuticociliates are extracellular histophagous parasites that affect farmed fish worldwide. One of the most common pathogenic species is Miamiensis avidus, a pathogen of New Zealand groper (Polyprion oxygeneios). The aim of this study was to characterise both the host (groper)-parasite (M. avidus) immune interactions and the possible protective role of dietary sodium ascorbate. Head-kidney leucocytes (HKLs) from naturally infected adult groper showed decreased respiratory burst response and peroxidase (Px) levels than healthy individuals. Infected groper also had significantly higher serum Px levels compared to controls. Myeloperoxidase (MPO) was inhibited in the head-kidney (HK) whereas MPO(+) cells were observed in the skin and muscle lesions. The inhibition of the innate immune responses was further studied in experimental infections with M. avidus, which confirmed depletion of Px inside leucocytes and marked increases in serum Px in infected individuals. Groper juveniles were fed a diet supplemented with sodium ascorbate (Vitamin C) (2g Kg(-1)) for 21 days and then challenged by subcutaneous injection or immersion exposure with live M. avidus cells. No protection was observed in the sodium ascorbate fed groper compared to the control diet following challenge by either injection or immersion. In vitro assays showed that sodium ascorbate itself results in the inhibition of Px and respiratory burst of groper HKLs, supporting the results obtained in vivo. Our results show that histophagous protozoa such as M. avidus hamper innate immune defences of fish hosts and that dietary sodium ascorbate does not protect groper against experimental infection with this parasite.

Polyketide assembly lines of uncultivated sponge symbionts from structure-based gene targeting.

There is increasing evidence that uncultivated bacterial symbionts are the true producers of numerous bioactive compounds isolated from marine sponges. The localization and heterologous expression of biosynthetic genes could clarify this issue and provide sustainable supplies for a wide range of pharmaceuticals. However, identification of genes in the usually highly complex symbiont communities remains a challenging task. For polyketides, one of the most important groups of sponge-derived drug candidates, we have developed a general strategy that allows one to rapidly access biosynthetic gene clusters based on chemical moieties. Using this method, we targeted polyketide synthase genes from two different sponge metagenomes. We have obtained from a sponge-bacterial association a complete pathway for the rare and potent antitumor agent psymberin from Psammocinia aff. bulbosa. The data support the symbiont hypothesis and provide insights into natural product evolution in previously inaccessible bacteria.

Anti-inflammatory and antimalarial meroterpenoids from the New Zealand ascidian Aplidium scabellum.

Bioassay-directed fractionation of an extract of the New Zealand ascidian Aplidium scabellum has afforded the anti-inflammatory secondary metabolite 2-geranyl-6-methoxy-1,4-hydroquinone-4-sulfate (1) and a family of pseudodimeric meroterpenoids scabellones A (2)-D (5). The benzo[c]chromene-7,10-dione scaffold contained within scabellones A-D is particularly rare among natural products. The structures were elucidated by interpretation of NMR data. Scabellone B was also identified as a moderately potent, nontoxic inhibitor of Plasmodium falciparum.

Didemnidines A and B, indole spermidine alkaloids from the New Zealand ascidian Didemnum sp.

Two new indole spermidine alkaloids, didemnidines A (1) and B (2), have been isolated from the New Zealand ascidian Didemnum sp. The structures of the metabolites, determined by analysis of 2D NMR spectra and confirmed via synthesis, embody an indole-3-glyoxylamide moiety linked to the N(1) position of spermidine, the latter motif being particularly rare among marine natural products. Didemnidine B and a synthetic precursor exhibited mild in vitro growth inhibition of Plasmodium falciparum with IC(50)'s of 15 and 8.4 µM, respectively.

Improving medical residents' utilisation of integrated mental health in primary care.

BACKGROUND: Integration of mental health services allows for improved prevention and management of chronic conditions within the primary care setting. This quality improvement project aimed to increase adherence to and functioning of an integrated care model within a patient-centred medical home. Specifically, the project focused on improving collaboration between Primary Care Mental Health Integration (PC-MHI) and the medical resident Patient Aligned Care Teams (PACT) at a Veterans Affairs Medical Center in Northport,New York (VAMC Northport). METHOD: The project used increased education, training and relationship building among the medical resident PACTs, and the establishment of regularly occurring integrated team meetings for medical and mental health providers. Education of residents was measured with a self-assessment pre-training and post-training, while utilisation was measured by the percentage of patients currently on a PACT's panel with at least one PC-MHI encounter in the last 12 months (known in VAMC Northport as PACT-15 metric). RESULTS: Two resident PACTs that received both training and weekly integrated meetings increased their utilisation of integrated mental health services by 3.8% and 4.5%, respectively. PACTs that participated in training only, with no regular meetings, showed an initial improvement in utilisation that declined over time. CONCLUSIONS: Training alone appeared beneficial but insufficient for increased integration over time. The addition of a regularly occurring integrated weekly meeting may be a critical component of facilitating sustained mental health integration in a primary care medical home model.

Rossinones A and B, biologically active meroterpenoids from the Antarctic ascidian, Aplidium species.

Rossinones A (1) and B (2), biologically active meroterpene derivatives, were isolated from an Antarctic collection of the ascidian Aplidium species and structurally characterized with spectroscopic methods. The absolute configuration of 1 was deduced by using the modified Mosher method. The rossinones exhibit anti-inflammatory, antiviral and antiproliferative activities.

Enantiomeric discorhabdin alkaloids and establishment of their absolute configurations using theoretical calculations of electronic circular dichroism spectra.

Enantiomeric pairs of the cytotoxic pyrroloiminoquinone marine alkaloids discorhabdins B (2), G*/I (3), L (4), and W (5) have been isolated from Latrunculia species sponges collected at different locations around the coast of New Zealand. The absolute configuration of all compounds was secured by comparison of observed data with the results of time-dependent density functional theory (TDDFT) calculations of electronic circular dichroism (ECD) spectra. Enantiomeric discorhabdins exhibit equipotent antiproliferative biological activity.

Synthesis and anti-inflammatory structure-activity relationships of thiazine-quinoline-quinones: inhibitors of the neutrophil respiratory burst in a model of acute gouty arthritis.

Sixteen new thiazine-quinoline-quinones have been synthesised, plus one bicyclic analogue. These compounds inhibited neutrophil superoxide production in vitro with IC(50)s as low 60 nM. Compounds with high in vitro anti-inflammatory activity were also tested in a mouse model of acute inflammation. The most active compounds inhibited both neutrophil infiltration and superoxide production at doses 2.5 micromol/kg, highlighting their potential for development as novel NSAIDs.

Binge-eating disorder and the outcome of bariatric surgery in a prospective, observational study: Two-year results.

OBJECTIVE: A previous study reported that preoperative binge-eating disorder (BED) did not attenuate weight loss at 12 months after bariatric surgery. This report extends the authors' prior study by examining weight loss at 24 months. METHODS: A modified intention-to-treat population was used to compare 24-month changes in weight among 59 participants treated with bariatric surgery, determined preoperatively to be free of a current eating disorder, with changes in 33 surgically treated participants with BED. Changes were also compared with 49 individuals with obesity and BED who sought lifestyle modification for weight loss. Analyses included all available data points and were adjusted for covariates. RESULTS: At month 24, surgically treated patients with BED preoperatively lost 18.6% of initial weight, compared with 23.9% for those without BED (P = 0.049). (Mean losses at month 12 had been 21.5% and 24.2%, respectively; P = 0.23.) Participants with BED who received lifestyle modification lost 5.6% at 24 months, significantly less than both groups of surgically treated patients (P < 0.001). CONCLUSIONS: These results suggest that preoperative BED attenuates long-term weight loss after bariatric surgery. We recommend that patients with this condition, as well as other eating disturbances, receive adjunctive behavioral support, the timing of which remains to be determined.

Sequence analysis of 16S rRNA gene of cyanobacteria associated with the marine sponge Mycale (Carmia) hentscheli.

Marine sponges frequently contain a complex mixture of bacteria, fungi, unicellular algae and cyanobacteria. Epifluorescent microscopy showed that Mycale (Carmia) hentscheli contained coccoid cyanobacteria. The 16S rRNA gene was amplified, fragments cloned and analysed using amplified rRNA gene restriction analysis. The nearly complete 16S rRNA gene of distinct clones was sequenced and aligned using ARB. The phylogenetic analysis indicated the presence of four closely related clones which have a high (8%) sequence divergence from known cyanobacteria, Cyanobacterium stanieri being the closest, followed by Prochloron sp. and Synechocystis sp. All belong to the order Chroococcales. The lack of non-molecular evidence prevents us from proposing a new genus.

Axis I psychopathology in bariatric surgery candidates with and without binge eating disorder: results of structured clinical interviews.

BACKGROUND: Prior studies have reached contradictory conclusions concerning whether binge eating disorder (BED) is associated with greater psychopathology in extremely obese patients who seek bariatric surgery. This study used the Structured Clinical Interview for DSM-IV Diagnoses (SCID) to compare rates of axis I psychopathology in surgery candidates who were determined to have BED or to be currently free of eating disorders. The relationship of BED to other psychosocial functioning and weight loss goals also was examined. METHODS: One hundred ninety five bariatric surgery patients completed the Weight and Lifestyle Inventory and the Beck Depression Inventory-II (BDI-II) and were later administered the Eating Disorder Examination. Of these 195, 44 who were diagnosed with BED, and 61 who were currently free of eating pathology, completed a telephone-administered SCID. RESULTS: Significantly more BED than non-BED participants had a current mood disorder (27.3% vs. 4.9%, p = 0.002) as well as a lifetime history of this condition (52.3% vs. 23.0%, p = 0.003). More BED than non-BED participants also had a current anxiety disorder (27.3% vs. 8.2%, p = 0.014) and lifetime anxiety disorder (36.4% vs. 16.4%, p = 0.019). BED also was associated with greater symptoms of depression, as measured by the BDI-II, as well as with lower self-esteem. BED and non-BED groups, however, did not differ in their desired weight loss goals following surgery. CONCLUSIONS: The present findings indicate that the presence of BED, in patients who seek bariatric surgery, is associated with an increased prevalence of axis I psychopathology, beyond the already elevated rate observed with severe (i.e., class III) obesity.

Binge eating disorder and the outcome of bariatric surgery at one year: a prospective, observational study.

Previous studies have suggested that binge eating disorder (BED) impairs weight loss following bariatric surgery, leading some investigators to recommend that patients receive behavioral treatment for this condition before surgery. However, many of these investigations had significant methodological limitations. The present observational study used a modified intention-to-treat (ITT) population to compare 1-year changes in weight in 59 surgically treated participants, determined preoperatively to be free of a current eating disorder, with changes in 36 individuals judged to have BED. Changes in weight and binge eating in the latter group were compared with those in 49 obese individuals with BED who sought lifestyle modification for weight loss. BED was assessed using criteria proposed for the Diagnostic and Statistical Manual (DSM) 5. At 1 year, surgically treated participants without BED lost 24.2% of initial weight, compared with 22.1% for those with BED (P > 0.309). Both groups achieved clinically significant improvements in several cardiovascular disease (CVD) risk factors. Participants with BED who received lifestyle modification lost 10.3% at 1 year, significantly (P < 0.001) less than surgically treated BED participants. The mean number of binge eating days (in the prior 28 days) fell sharply in both BED groups at 1 year. These two groups did not differ significantly in BED remission rates or in improvements in CVD risk factors. The present results, obtained in carefully studied participants, indicate that the preoperative presence of BED does not attenuate weight loss or improvements in CVD risk factors at 1 year in surgically treated patients. Longer follow-up of participants is required.

Behavioral and pharmacologic therapies for obesity.

This article reviews novel developments in the behavioral and pharmacologic treatment of obesity and explores the potential contribution of genomics research to weight control. A comprehensive program of lifestyle modification, comprised of diet, physical activity and behavior therapy, induces a mean loss of 7-10% of initial weight in individuals with obesity. Two trials demonstrated that weight loss of this magnitude, combined with increased physical activity, substantially reduced the risk of developing type 2 diabetes mellitus in individuals with impaired glucose tolerance. A third trial is now investigating whether lifestyle intervention will reduce cardiovascular morbidity and mortality in overweight individuals who already have diabetes mellitus. Pharmacotherapy is recommended, in some patients, as an adjunct to lifestyle modification. Two medications-orlistat and sibutramine-are currently approved in the US for long-term weight loss. Both are efficacious when combined with lifestyle modification, although health concerns have been raised about the use of sibutramine. Several novel combination therapies, which target multiple hypothalamic pathways that regulate appetite and body weight, are currently under investigation. Genomic studies provide further evidence for the role of these pathways in the regulation of body weight. Identification of new genes controlling satiety and energy expenditure may yield valuable clues for the development of novel pharmacologic treatments.

In vitro culture and cryopreservation of Uronema marinum isolated from farmed New Zealand groper (Polyprion oxygeneios).

An in vitro culture method was developed for the ciliated protozoa Uronema marinum isolated from New Zealand aquacultured groper (Polyprion oxygeneios). Both formulated media and sterile seawater supplemented with homogenised fish tissue as a food source supported growth of U. marinum achieving cell densities of up to 1 x 10(5)cells/mL in culture. A cryopreservation method based on a cryomix formula of 20% glycerol, 10% fetal bovine serum and 70% cultured U. marinum, incorporating a slow freeze method to -80 degrees C, then liquid nitrogen storage, allowed cryogenic storage of cells and successful re-culture up to 12 months in storage.

An antiproliferative bis-prenylated quinone from the New Zealand brown alga Perithalia capillaris.

Bioactivity-directed isolation work on the endemic New Zealand brown alga Perithalia capillaris, seeking anti-inflammatory compounds, led to a new bis-prenylated quinone ( 4). This compound inhibited superoxide production by human neutrophils in vitro (IC 50 2.1 microM), but was more potent at inhibiting proliferation of HL60 cells (IC 50 0.34 microM). Two related bis-prenylated phenols were also isolated, one known ( 2) and one new ( 5), with weaker biological activities. This report extends the examples of bis-prenylated phenols as chemotaxonomic markers for brown algae of the order Sporochnales.

E/Z-rubrolide O, an anti-inflammatory halogenated furanone from the New Zealand ascidian Synoicum n. sp.

Bioassay-directed fractionation of extracts of a Synoicum n. sp. ascidian from New Zealand led to the isolation of the principal anti-inflammatory component, which was identified by spectroscopic methods as a new member of the rubrolide family, rubrolide O (1), existing as a mixture of E/Z isomers.