Associations between diet composition, dietary pattern, and weight outcomes after bariatric surgery: a systematic review.

INTRODUCTION: Literature describing the impact of dietary intake on weight outcomes after bariatric surgery has not been synthesized. This study aimed to synthesize the evidence regarding any association between diet composition and weight outcomes post-bariatric surgery. METHODS: CINAHL, Cochrane, Embase, MEDLINE and Scopus were searched for adult studies up to June 2021 that assessed any association between dietary intakes (≥1-macronutrient, food group, or dietary pattern) and weight outcomes at 12-months or longer after bariatric surgery. Risk of bias and quality assessments were conducted using the Scottish Intercollegiate Guidelines Network checklists and the NHMRC's Level of Evidence and Grades for Recommendations. Study findings were presented according to the time of post-surgery dietary intake assessment (≤12months, between 12 and 24 months, ≥24months). RESULTS: 5923 articles were identified, 260 were retrieved for full text screening, and 36 were eligible for inclusion (9 interventional including five randomized-controlled trials, and 27 observational cohort studies; sample sizes: 20-1610; total sample: 5065; follow-up periods: 1 year-12 years; level of evidence: II to IV, risk of bias: low to high). Findings on the association between long-term weight outcomes and dietary composition up to 24-months were mixed. After 24-months, studies consistently suggested no significant associations between weight loss and macronutrient composition or core food group patterns, or between carbohydrate, protein or food group patterns and weight recurrence. A single cohort study reported a weak association between diet quality score and weight-recurrence after 24-months. CONCLUSION: There was no strong evidence to support significant associations between diet composition and weight outcomes post-bariatric surgery. The heterogeneity in study design and quality may reduce generalizability to external populations. Individualized dietary recommendations may be useful to support long-term post-surgery weight outcomes. More studies are needed to define and measure diet quality in this patient cohort. REGISTRATION: PROSPERO (CRD42021264120).

A self-determination theory analysis of reflective debrief themes about dietetic student placement experiences in hospital: implications for education.

BACKGROUND: Healthcare placements in dietetics education contribute significantly to student learning. Exploring students' self-conceptualisation of placement experiences may provide insights to better support learning. Self-determination theory (SDT) has been used to seek insight into clinical and educational settings but has not yet been applied to dietetic placement learning. The present study investigated dietetics students' reflections of key influences on placement learning experiences and their alignment with an SDT framework. METHODS: A post-placement two-stage critical incident debrief was conducted with seven successive cohorts (168 students) of dietetic undergraduate students on final placement. In debriefs, students' anonymous themes were collected and discussed, inductively analysed, and then mapped against an SDT framework of psychological and motivational constructs. RESULTS: Nine key themes were identified that impacted upon placement experiences. Four themes related to framework constructs: (1) Supervisor (and Peer) Autonomy Support; (2) Perceived Competence; (3) Relatedness; and (4) Autonomy and Intrinsic Motivation. Non-SDT themes were also present, including: (5) Learning Environment and Experience; as well as themes about professional behaviours and identity: (6) Teamwork and Interactions; (7) Managing Emotions and Self-Care; (8) Dietetic Communications and Behaviours; and (9) Developing a Professional Identity. CONCLUSIONS: Embedding a structured debrief in the curriculum and using a psychological motivational SDT framework to analyse themes arising can provide valuable information about the learning needs of students on placement with potential for wider application in dietetic learning and teaching and workforce employability. The current findings may have application in university curricula before and after professional placement.

Efficacy of a dietitian-led very low calorie diet (VLCD) based model of care to facilitate weight loss for obese patients prior to elective, non-bariatric surgery.

BACKGROUND: Elective surgery in obese adults carries a higher risk of post-operative infection and prolonged hospital stays, and surgeons may postpone surgery for patients with obesity until they lose weight. The present study aimed to determine the efficacy of a dietitian-led very low calorie diet (VLCD)-based model of care with respect to achieving weight loss for obese patients prior to surgery. METHODS: This mixed-methods study included a medical chart audit of patients referred to a VLCD-based model over 23 months, as well as a survey of recently treated patients and surgeons who utilised the model. Preoperative weight loss targets were set by surgeons, and the dietitian prescribed individualised VLCD-based treatment. Efficacy was determined as weight loss considered sufficient for surgery, clinical safety of VLCD-based treatment, feasibility, and stakeholder value. Pre/post-intervention differences in clinical measures were explored by paired t-test or Wilcoxon tests as appropriate. RESULTS: Data on seventy-eight eligible patients [mean (SD) 45 (13) years, 90% female, body mass index 44.3 (6.2) kg m-2 ] demonstrated significant mean (SD) weight loss of 7.4% (5.3%) body weight (P < 0.05). Most patients (70%, n = 50/71) achieved sufficient weight loss to proceed to surgery. Fifty-six per cent of patients reported mild side effects (n = 43/77) and none led to treatment cessation. Surgeons reported VLCD-based treatment made operations easier (83%, n = 10/12) and shorter (75%, n = 9/12) and all recommended the model of care. All surveyed patients (n = 24) reported satisfaction with their VLCD-based model experience. CONCLUSIONS: A dietitian-led VLCD-based model achieved sufficient weight loss to facilitate elective surgery for most patients. The approach was feasible, highly valued by patients and surgeons, and resulted in perceived surgical benefits.

Quality of development and reporting of dietetic intervention studies in primary care: a systematic review of randomised controlled trials.

BACKGROUND: High-quality research methodologies and clear reporting of studies are essential to facilitate confidence in research findings. The aim of the present study was to conduct an in-depth examination of the methodological quality and reporting of studies included in a recent systematic review of dietitians' effectiveness at providing individualised nutrition care to adult patients. METHODS: The methodological quality and reporting of 27 Randomised Controlled Trials (RCTs) were appraised using the UK Medical Research Council (MRC) Guidelines for complex interventions and the CONSORT checklist for reporting RCTs. A quality appraisal checklist was developed for each guideline/assessment tool aiming to evaluate the extent to which each study met the designated criteria. Excerpts from studies that best addressed criteria were collated to provide exemplary accounts of how criteria may be achieved in future studies. RESULTS: None of the reviewed studies met more than half of the MRC Guidance criteria, indicating that there is clear room for improvement in reporting the methodological underpinnings of these studies. Similarly, no studies met all criteria of the CONSORT checklist, suggesting that there is also room for improvement in the design and reporting of studies in this field. CONCLUSIONS: Dietitians, researchers and journal editors are encouraged to use the results and exemplary accounts from this review to identify key aspects of studies that could be improved in future research. Improving future research will enhance the quality of the evidence-base that investigates the outcomes of dietary interventions involving dietitians.

Is it possible to enhance the confidence of student dietitians prior to professional placements? A design-based research model.

BACKGROUND: Student confidence is an important contributor to a successful professional placement experience. The present study aimed to evaluate a placement preparation program for student dietitians and to assess the impact on self-rated confidence with respect to commencing placements. METHODS: The present study is part of a design-based research approach that involves students in a cyclic enquiry to evaluate and improve curricula. Nutrition and Dietetics students at an Australian university participated in a 1-week mandatory workshop - Pre-Placement week (PrePW), N = 98 students: in 2015 (n = 54) and 2016 (n = 44). An online survey was conducted before and after PrePW using a five-point Likert scale (1 = not confident; 5 = very confident) to assess self-rated confidence to commence placements. Mean (SD) scores were calculated. Paired and independent t-tests evaluated within- and between-group differences, respectively. RESULTS: Before PrePW, the mean (SD) for student confidence to commence placements overall (in all areas of practise) was 'somewhat confident' [2.9 (0.6) in 2015 and 3.0 (0.7) in 2016]. Students were least confident to commence Clinical Practice [2015: 2.5 (0.6); 2016: 2.8 (0.6)] compared to Food Service Management (FSM) [2015: 3.2 (0.9); 2016: 3.1 (0.9)] and Community and Public Health Nutrition (CPHN) [2015: 3.3 (0.9); 2016: 3.2 (0.8)]. Student feedback from PrePW 2015 was used to change the curriculum and PrePW program. The 2016 students reported significantly greater confidence within all areas of practice: Clinical Practice [3.4 (0.6)], FSM [3.7 (0.6)] and CPHN [3.8 (0.6)], including confidence to commence placements overall [3.6 (0.6)] (P < 0.05). CONCLUSIONS: Design-based research provides a useful framework for improvement to curricula and, in this case, was successful in enhancing student confidence in preparation for professional placement.

Pressure ulcer healing with an intensive nutrition intervention in an acute setting: a pilot randomised controlled trial.

OBJECTIVE: To investigate the feasibility of recruitment, retention, intervention delivery and outcome measurement in a nutritional intervention to promote pressure ulcer healing in an acute setting. METHOD: Some 50 tertiary hospital patients with stage II or greater pressure ulcer were randomised to receive either individualised nutritional care by a dietitian, including prescription of wound healing supplements; or standard nutritional care. Relevant nutritional and pressure ulcer (PU) parameters were collected at day 5, 10, 15, 22 and then weekly or until discharge. RESULTS: The median length of hospital stay was 14 days (1-70) with 29 patients discharged by day 15. There were 24 patients discharged before their PU fully healed. Per cent change in valid PU area and score measures from baseline to day 15 were chosen for outcome data analysis to account for varying initial size and severity of the wound and length of stay. There was a larger percentage reduction in PU measures in the intervention group, but this was not statistically significant. Little difference was found in nutritional intake between the control and intervention groups indicating a requirement to focus on effective delivery of the intervention in future studies. Future studies in the acute setting need to account for length of stay and ideally follow patients until full healing. CONCLUSION: Results indicate a positive association with nutrition intervention and PU healing and that a rigorously designed and adequately powered study is feasible. DECLARATION OF INTEREST: This research was supported by a grant from the Queensland Health, Health Practitioner Research Scheme. The authors have no conflicts of interest to declare.

PCDH11 is X/Y homologous in Homo sapiens but not in Gorilla gorilla and Pan troglodytes.

Protocadherin X (PCDHX) and Protocadherin Y (PCDHY) are cell-surface adhesion molecules expressed predominantly in brain. The human PCDH11X/Y gene pair is located in the non-pseudoautosomal X-Y homologous region (Xq21.3/Yp11.2). The possible existence of PCDH11 gene dosage differences between human and non-human primates is of evolutionary significance with respect to species differences and escape from X inactivation, and has been repeatedly debated. Previous investigations on the X/Y homologous status of PCDH11 and adjacent sequences in non-human primates have highlighted the complexity of the molecular pattern and evolutionary history of this genomic region. This paper provides for the first time direct evidence for the absence of the PCDH11 genefrom the Y chromosome of chimpanzee (Pan troglodytes) as well as gorilla (Gorilla gorilla). By confirmingthe suspected lack of X-Y homologous status for PCDH11 in non-human primates, our results reinforce the hypothesis of a hominid-specific role for this gene in brain development.

Substrate deformation in a hypoxanthine-guanine phosphoribosyltransferase ternary complex: the structural basis for catalysis.

BACKGROUND: Hypoxanthine-guanine phosphoribosyltransferases (HGPRTs) are well-recognized antiparasitic drug targets. HGPRT is also a paradigmatic representative of the phosphoribosyltransferase family of enzymes, which includes other important biosynthetic and salvage enzymes and drug targets. To better understand the reaction mechanism of this enzyme, we have crystallized HGPRT from the apicomplexan protozoan Toxoplasma gondii as a ternary complex with a substrate and a substrate analog. RESULTS: The crystal structure of T. gondii HGPRT with the substrate Mg2+-PRPP and a nonreactive substrate analog, 9-deazaguanine, bound in the active site has been determined at 1.05 A resolution and refined to a free R factor of 15.4%. This structure constitutes the first atomic-resolution structure of both a phosphoribosyltransferase and the central metabolic substrate PRPP. This pre-transition state complex provides a clearer understanding of the structural basis for catalysis by HGPRT. CONCLUSIONS: Three types of substrate deformation, chief among them an unexpected C2'-endo pucker adopted by the PRPP ribose ring, raise the energy of the ground state. A cation-pi interaction between Tyr-118 and the developing oxocarbenium ion in the ribose ring helps to stabilize the transition state. Enforced substrate propinquity coupled with optimal reactive geometry for both the substrates and the active site residues with which they interact contributes to catalysis as well.

Nature of genetic resistance to Marek's disease in chickens.

Infection of line 6 resistant and line 7 susceptible chickens with Marek's disease virus (MDV) resulted in a depressed phytohemagglutinin (PHA) response and the presence of Marek's disease (MD) tumor-associated surface antigen (MATSA) in the spleens. At 6-10 weeks after infection, recovery in PHA response, diminution in the number of MATSA cells, and the presence of significant anti-MATSA immunity were observed in line 6 but not in line 7 chickens. Both lines had antibody-dependent cell-mediated antiviral immunity, but T-cell-mediated antiviral immunity was detected only in line 6 and the surviving line 7 chickens. Lymphoproliferative lesions were found only in line 7 chickens, an virus titers were significantly higher in line 7 than in line 6 chickens and embryos. Lymphoid organ weights and the number of lymphocytes of line 6 were significantly lower than those of line 7. These data suggests that resistance to MD in line 6 chickens was due to a) a deficiency in the aggregate number of target lymphocytes, b) a restriction in the ability to lymphocytes to nonproductively replicate MDV, and c) the involvement of cellular antiviral and antitumor immune responses.

Basolateral but not apical application of protease results in a rapid rise of transepithelial electrical resistance and formation of aberrant tight junction strands in MDCK cells.

In the presence of Ca2+, application of trypsin to the basolateral surface of confluent MDCK cell monolayers with formed tight junctions (TJ), induces the formation of basolaterally oriented aberrant TJ strands. Induction of aberrant TJ strands is accompanied by an increase in transepithelial electrical resistance (TER), up to 90%, which upon addition of trypsin inhibitor is maintained for up to 1 h. Thereafter TER returns slowly to baseline values. Under similar conditions, application of trypsin to the apical surface has little or no effect on either TER or the number of aberrant TJ strands. Confocal microscopy of monolayers, immunostained for ZO-1, revealed that this TJ associated cytoplasmic protein, extended below the TJ along the basolateral surface following brief exposure to trypsin. Removing Ca2+ after treatment of the monolayer with basolaterally applied trypsin resulted, after 20 min, in the increased partitioning of TJ particles onto the E fracture face, of both normal and aberrant TJ strands. Like the TJ strands themselves, therefore, aberrant strands may be linked to cytoskeletal elements. Aberrant TJ strands do not form when monolayers, maintained in low Ca2+ medium, are exposed to trypsin, suggesting that under these conditions TJ precursors, and/or trypsin-sensitive proteins regulating TJ strand assembly, are sequestered in a vesicular compartment that is inaccessible to exogenous trypsin. Prolonged exposure of the apical surface of an established, polarized epithelium with intact TJ to trypsin, had little effect on TJ integrity and did not induce aberrant strands.

Lack of synergy in the inhibition of HIV-1 reverse transcriptase by combinations of the 5'-triphosphates of various anti-HIV nucleoside analogs.

3'-Deoxy-3'-azidothymidine (AZT) has been shown to synergistically inhibit the replication of human immunodeficiency virus type 1 (HIV-1) in cell culture when combined with several other 2',3'-dideoxynucleoside analogs. In an effort to understand the biochemical mechanism of this synergy, we have examined the effect of combinations of the 5'-triphosphate of AZT (AZT-TP) with either ddCTP, ddATP, or the 5'-triphosphate of the carbocyclic analog of 2',3'-didehydro-2',3'-dideoxyguanosine (carbovir) on both the RNA-directed and DNA-directed DNA polymerase activity of HIV-1 reverse transcriptase. Kinetic studies, which evaluated the ability of these combinations to competitively inhibit the enzyme, showed that AZT-TP could not bind to the enzyme with either the RNA or DNA template at the same time as either of the other three inhibitors. None of these analogs could affect the incorporation of another analog into the DNA chain by the HIV-1 reverse transcriptase. These results indicated that synergistic inhibition of the HIV-1 reverse transcriptase is not responsible for the synergistic antiviral activity seen in cell culture with combinations of these nucleoside analogs.

A TIBO derivative, R82913, is a potent inhibitor of HIV-1 reverse transcriptase with heteropolymer templates.

R82913, (+)-S-4,5,6,7-tetrahydro-9-chloro-5-methyl-6-(3-methyl-2-butenyl)- imidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione (a TIBO derivative), inhibited the replication of thirteen different strains of HIV-1 in CEM cells with a median IC50 of 0.15 microM. The concentration of compound that killed 50% of the cells was much higher (46 microM), indicating that R82913 has a high selectivity index. R82913 was 20-fold more potent than AZT-TP in the inhibition of HIV-1 reverse transcriptase in an assay using a naturally occurring template (ribosomal RNA) that more accurately resembles native viral RNA than a synthetic homopolymer. With this template, R82913 inhibited HIV-1 reverse transcriptase with an ID50 (0.01 microM) that is equal to, or lower than, the IC50 for this compound in all of our cell culture assays (0.01-0.65 microM). R82913 has no effect on the replication of HIV-2 in CEM cells and does not inhibit the reverse transcriptase from this virus.

Interference with HIV-1 reverse transcriptase-catalyzed DNA chain elongation by the 5'-triphosphate of the carbocyclic analog of 2'-deoxyguanosine.

In an effort to better understand features in nucleotide analogs that result in the inhibition of HIV-1 reverse transcriptase, we have evaluated this enzyme with the 5'-triphosphate of the carbocyclic analog of 2'-deoxyguanosine (CdG-TP). CdG-TP was a reasonably potent competitive inhibitor of the incorporation of dGTP into DNA by HIV-1 reverse transcriptase using either a RNA or DNA template (Ki, 1 microM). CdG-TP was a good substrate for HIV-1 reverse transcriptase on both templates, but the DNA chain was poorly extended beyond the incorporation of CdG. These results indicate that substitution of ribose with a cyclopentane ring in nucleotides is not well tolerated by HIV-1 reverse transcriptase.

Thiazolobenzimidazole: biological and biochemical anti-retroviral activity of a new nonnucleoside reverse transcriptase inhibitor.

Thiazolobenzimidazole (NSC 625487) was a highly potent inhibitor of human immunodeficiency virus-induced cell killing and viral replication in a variety of human cell lines, as well as fresh human peripheral blood lymphocytes and macrophages. The compound was active against a panel of biologically diverse laboratory and clinical strains of HIV-1, including the AZT-resistant strain G910-6. However, the agent was inactive against HIV-2 and a pyridinone-resistant strain (A17) of HIV-1, a strain which is cross-resistant to several structurally diverse members of a common pharmacologic class of nonnucleoside reverse transcriptase inhibitors. The compound selectively inhibited HIV-1 reverse transcriptase but not HIV-2 reverse transcriptase. Combinations of thiazolobenzimidazole with either AZT or ddI synergistically inhibited HIV-1 induced cell killing in vitro. Thiazolobenzimidazole also inhibited the replication of the Rauscher murine leukemia retrovirus. Thus, thiazolobenzimidazole is a new active anti-HIV-1 chemotype and may represent a subclass of nonnucleoside reverse transcriptase inhibitors with an enhanced range of anti-retroviral activity.

PMTI, a broadly active unusual single-stranded polyribonucleotide, inhibits human immunodeficiency virus replication by multiple mechanisms.

Poly(1-methyl-6-thioinosinic acid), or PMTI, is a single-stranded polyribonucleotide and is the first homopolyribonucleotide devoid of Watson-Crick hydrogen bonding sites to show potent human immunodeficiency virus (HIV) inhibition. PMTI was found to be active when evaluated against a variety of low passage clinical HIV isolates in fresh human peripheral blood cells, including T cell-tropic and monocyte-macrophage-tropic viruses, syncytium-inducing and non-syncytium-inducing viruses and viruses representative of the various HIV-1 clades (A through F). The compound was active against HIV-2, all nucleoside and non-nucleoside reverse transcriptase (RT) inhibitor drug-resistant virus isolates tested and interacted with AZT or ddl to synergistically inhibit HIV infection. In biochemical inhibition assays, PMTI was determined to be a potent inhibitor of HIV-1 and HIV-2 RT, including RTs with mutations that engender resistance to nucleoside and non-nucleoside RT inhibitors. PMTI inhibited both the polymerase and RNase H activities of HIV RT. PMTI did not inhibit HIV-1 protease or integrase. Cell-based mechanism of action assays indicated that PMTI also interfered with early events in the entry of HIV into target cells. Furthermore, PMTI inhibited the fusion of gp120-expressing and CD4-expressing cells, but at concentrations approximately 1 log10 greater than those that inhibited virus entry. These results suggest that the homopolyribonucleotide PMTI blocks HIV replication in human cells at its earliest stages by multiple mechanisms, inhibition of virus entry and inhibition of RT.

Screening of potential cancer-preventing chemicals for inhibition of induction of ornithine decarboxylase in epithelial cells from rat trachea.

Sixty-one selected chemicals were evaluated in rat tracheal epithelial (2C5) cells for their capacity to inhibit induction (or inhibit directly) the enzyme ornithine decarboxylase, the activity of which is associated with cell growth and division. a-Difluoromethylornithine (DFMO) was used as a positive control. At non-toxic concentrations, six test compounds had substantial activity (values for IC50 DFMO/IC50 compound >1): N-(2-carboxyphenyl)-all-trans-retinamide, ZK 119010 ¿2-(4-hydroxyphenyl)-3-methyl-1-[6-(1-pyrrolidinyl)hexyl]-1H-indol-5- ol¿, curcumin, 18-a-olean-12-ene-3 ,23,28-triol, genistein and phenethyl isothiocyanate. These should be considered for further development as cancer preventive agents.

Screening of potential cancer preventing chemicals for induction of glutathione in rat liver cells.

With BRL 3A hepatocytes, a series of selected, potentially chemopreventive chemicals was evaluated for their capacity to elevate glutathione (GSH) levels. Since sodium selenite consistently increased GSH levels by approximately 70%, it was selected as a positive control. Of 62 test chemicals, eighteen stimulated GSH levels by >30%, but eleven of these had only a modest effect or displayed considerable toxicity. At non-toxic concentrations, seven compounds had substantial activity: black tea extract (decaffeinated), trans-chalcone, N-ethyl-9-cis-retinamide, indole-3-carbinol, dehydroepiandrosterone (DHEA) curcumin and N-(4-carboxyphenyl)retinamide. These should be considered for further development as cancer preventive agents.

Screening of potential cancer preventing chemicals as antioxidants in an in vitro assay.

We used an azo-initiated fluorescence assay to rank a series of antioxidants, with the objective of selecting compounds for further evaluation as chemopreventive agents. Trolox was the positive control for the assay and, with an IC50 of 0.50 microM, was more active than any of the other 16 compounds examined. Three compounds, U83836E, glutathione, and purpurgallin, were only slightly less active with IC50's in the 1-3 microM range. Four other compounds were almost as active: protochatechuic acid, N-acetyl-L-cysteine, U74389G, and lipoic acid (reduced). This fluorescence-based assay for antioxidant activity is a rapid, economical way of ranking antioxidants for further development in the National Cancer Institute's chemoprevention program.

Screening of potential cancer preventing chemicals as aromatase inhibitors in an in vitro assay.

The inhibition of human placental aromatase was used to rank a series of compounds, with the objective of selecting compounds for further evaluation as chemopreventive agents. (+/-)-p-Aminoglutethimide, introduced over two decades ago as a treatment for breast cancer, had an IC50 of 6.5 microM. Five compounds were more potent than aminoglutethimide in this assay: (+)- vorozole, 4-hydroxyandrostenedione, miconazole nitrate, plomestane, and 4-methoxy-androst-4-ene-3,17-dione. Other compounds with known chemoprevention activity, such as curcumin and genistein, were inactive. This assay for aromatase inhibitors is a rapid, economical way of ranking compounds for further development as chemoprevention agents.

Antioxidant activity of michellamine alkaloids.

The alkaloids michellamines A, B, and C are natural products isolated from a Central African tropical plant Ancistrocladus korupensis. We have investigated the radical scavenging ability of these compounds. The alkaloids inhibited the azo-induced oxidation of beta-phycoerythrin with IC50 values in the 0.5- to 0.8-microM range. Michellamine B also protected rat liver mitochondria against lipid peroxidation induced by adenosine diphosphate and Fe2+. The alkaloids were more potent antioxidants in these assays than several compounds being considered clinically as chemoprevention agents.