Empowering Pacific Patients on the Weight Loss Surgery Pathway: A Co-designed Evaluation Study.

PURPOSE: Despite having the highest medical needs by population for weight loss treatment, Pacific patients in Aotearoa New Zealand face substantial levels of attrition in publicly funded weight loss surgery programs. In collaboration with the Auckland City Hospital bariatric surgery team, a Pacific-led preoperative weight loss surgery program was co-designed, delivered, and evaluated between 2020 and 2023. MATERIALS AND METHODS: This was a single-arm, prospective co-designed evaluation study that took place at Auckland City Hospital in Aotearoa New Zealand. Participants were Pacific patients (n = 14) referred to the weight loss surgery program. Survey and video diaries were analyzed to determine if the program had the potential to increase Pacific patient retention through the preoperative stage of weight loss surgery, increase surgery completion rates, and improve the quality of treatment experiences. RESULTS: Nine out of 14 participants attended all preoperative sessions. Six participants subsequently underwent weight loss surgery. Program components that had positive impacts on patient success and satisfaction were accessibility, information quality, having Pacific role models, cultural safety, and the group support system. The patients found the program to be culturally anchored and there was support for the implementation of the program going forward. CONCLUSION: This study demonstrated how a culturally anchored intervention can increase patient retention for those patients who may not respond to mainstream treatment. Adjusting existing preoperative weight loss surgery programs to integrate Pacific-led models of healthcare has the potential to increase Pacific patient resiliency to follow through with surgery.

Impact of Bariatric Surgery on Unplanned Hospital Admissions for Infection.

PURPOSE: Both obesity and type 2 diabetes are associated with an increased risk of skin and soft tissue (SSTI), urinary tract, and lower respiratory tract infections but it is not clear whether the incidence of such infections is reduced after bariatric surgery. MATERIALS AND METHODS: In people accepted onto our publicly funded bariatric program, we recorded unplanned admissions to public hospitals over a median follow-up of 4.5 years in those successfully undergoing surgery and in those who withdrew from the program. Rates of admission for the composite outcome (SSTI, urinary tract, or lower respiratory infection) were compared. RESULTS: Of 774 people accepted onto the program, 49% underwent surgery. Infections accounted for 27% of unplanned admissions in those not completing surgery and 13% of those who underwent surgery (p < 0.001). The rate of admission was 60% lower in people who underwent surgery than those who did not: 4.3 vs 12.2 per 100 patient-years (P < 0.002), a difference maintained across 8 years' follow-up. The impact of surgery was independent of enrolment age, BMI, or diabetes and smoking status. Of the three types of infection in the composite outcome, SSTI were the most prevalent and showed the greatest reduction (p < 0.0001). The median day stay for infection was 0.5 day less in those who underwent surgery (p < 0.01). CONCLUSIONS: Hospitalization for these three infectious diseases in people undergoing bariatric surgery was lower than that in people enrolled in the bariatric program but not completing surgery. The effect was greatest for SSTI, and sustained to at least 8 years.

Prevalence of Postoperative Infection after Tooth Extraction: A Retrospective Study.

The aim of the study was to identify the postoperative infection rates after tooth extraction in a university dental clinic and to identify the factors associated with an increased risk for postoperative infection. A retrospective study of case records of patients who underwent tooth extractions at the International Medical University's Oral Health Centre (IMU-OHC) over a span of 6 years was conducted. Data on demography, patient-related factors, and treatment-related factors were extracted from the case records. A binary logistic regression analysis was performed to assess the odds ratio of a patient having a postoperative infection or not, comparing it with each variable. A total of 1821 extractions, including simple and complex extractions, were performed over 6 years. Only 25 (1.4%) of the cases were reported to have a postoperative infection. The complexity of the extraction was the only variable that significantly affected the occurrence of postoperative infection after extraction; more complex extractions were reported with higher rates of infection (binary logistic regression, OR = 2.03, p = 0.004). None of the other factors, including antibiotic prescription, had a significant influence on the occurrence of postoperative infection. The prevalence of postoperative infection after dental extractions was low in IMU-OHC, and prescribing antibiotics had no added advantage in the prevention of postoperative infection.

Structure and Antioxidant Activities of Proanthocyanidins from Elephant Apple (Dillenia indica Linn.).

UNLABELLED: Proanthocyanidins were isolated and purified from fruits of elephant apple (Dillenia indica Linn.) and their structural and bioactive properties were examined. Bate-Smith alcoholysis, FTIR, and (13) C NMR spectra revealed that elephant apple proanthocyanidins (EAPs) contained a dominant amount of B-type procyanidins (PC) with a minor amount of B-type prodelphinidins (PD) but no A-type interflavan linkage. (13) C NMR spectrum indicated that the cis isomer was dominant in EAPs. The electron spray ionization and matrix-assisted laser desorption ionization time of flight mass spectra of EAPs showed the clear ion peaks corresponding to B-type PC dimer to B-type PD with degree of polymerization of 11. EAPs had strong antioxidant activity, which was evidenced by the high oxygen radical scavenging capacity at 1.06 × 10(4) µmol TE/g and ferric reducing antioxidant power of 2320 µmol Fe(II)/g. The results suggest that EAPs could be extracted to be used as promising functional food materials. PRACTICAL APPLICATION: In this study, the elephant apple proanthocyanidins (EAPs) with a yield of 0.23% were identified for the first time as dominant B-type poly(catechin/epicatechin) but no A-type interflavan linkage. EAPs had higher ORAC and FRAP values compared to commercial grape seed proanthocyanidins, suggesting that EAPs may be used as promising functional food materials.

PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis.

Directed cell migration involves signaling events that lead to local accumulation of PI(3,4,5)P(3), but additional pathways act in parallel. A genetic screen in Dictyostelium discoideum to identify redundant pathways revealed a gene with homology to patatin-like phospholipase A(2). Loss of this gene did not alter PI(3,4,5)P(3) regulation, but chemotaxis became sensitive to reductions in PI3K activity. Likewise, cells deficient in PI3K activity were more sensitive to inhibition of PLA(2) activity. Deletion of the PLA(2) homolog and two PI3Ks caused a strong defect in chemotaxis and a reduction in receptor-mediated actin polymerization. In wild-type cells, chemoattractants stimulated a rapid burst in an arachidonic acid derivative. This response was absent in cells lacking the PLA(2) homolog, and exogenous arachidonic acid reduced their dependence on PI3K signaling. We propose that PLA(2) and PI3K signaling act in concert to mediate chemotaxis, and metabolites of PLA(2) may be important mediators of the response.

Distinct roles of PI(3,4,5)P3 during chemoattractant signaling in Dictyostelium: a quantitative in vivo analysis by inhibition of PI3-kinase.

The role of PI(3,4,5)P(3) in Dictyostelium signal transduction and chemotaxis was investigated using the PI3-kinase inhibitor LY294002 and pi3k-null cells. The increase of PI(3,4,5)P(3) levels after stimulation with the chemoattractant cAMP was blocked >95% by 60 microM LY294002 with half-maximal effect at 5 microM. This correlated well with the inhibition of the membrane translocation of the PH-domain protein, PHcracGFP. LY294002 did not reduce cAMP-mediated cGMP production, but significantly reduced the cAMP response up to 75% in wild type and completely in pi3k-null cells. LY294002-treated cells were round, not elongated as control cells. Interestingly, cAMP induced a time and dose-dependent recovery of cell elongation. These elongated LY294002-treated wild-type and pi3k-null cells exhibited chemotactic orientation toward cAMP that is statistically identical to chemotactic orientation of control cells. In control cells, PHcrac-GFP and F-actin colocalize upon cAMP stimulation. However, inhibition of PI3-kinases does not affect the first phase of the actin polymerization at a wide range of chemoattractant concentrations. Our data show that severe inhibition of cAMP-mediated PI(3,4,5)P(3) accumulation leads to inhibition of cAMP relay, cell elongation and cell aggregation, but has no detectable effect on chemotactic orientation, provided that cAMP had sufficient time to induce cell elongation.

Novel mechanism of PTEN regulation by its phosphatidylinositol 4,5-bisphosphate binding motif is critical for chemotaxis.

In chemotaxing cells, localization of phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) to the leading edge of the cell sets the direction and regulates the formation of pseudopods at the anterior. We show that the lipid phosphatase activity of PTEN mediates chemotaxis and that the sharp localization of PI(3,4,5)P3 requires localization of PTEN to the rear of the cell. Our data suggest that a phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) binding motif at the N terminus of PTEN serves the dual role of localizing the enzyme to the membrane and regulating its activity. Mutations in this motif enhance catalytic activity but render the enzyme inactive in vivo by preventing membrane association. The key role of this motif may explain the heretofore puzzling tumor-suppressing mutations occurring within the PI(4,5)P2 binding motif. On the other hand, the localization of PTEN does not depend on its phosphatase activity, the actin cytoskeleton, or the intracellular level of PI(3,4,5)P3, suggesting that events controlling localization are upstream of phosphoinositide signaling.

Two phases of actin polymerization display different dependencies on PI(3,4,5)P3 accumulation and have unique roles during chemotaxis.

The directional movement of cells in chemoattractant gradients requires sophisticated control of the actin cytoskeleton. Uniform exposure of Dictyostelium discoideum amoebae as well as mammalian leukocytes to chemoattractant triggers two phases of actin polymerization. In the initial rapid phase, motility stops and the cell rounds up. During the second slow phase, pseudopodia are extended from local regions of the cell perimeter. These responses are highly correlated with temporal and spatial accumulations of PI(3,4,5)P3/PI(3,4)P2 reflected by the translocation of specific PH domains to the membrane. The slower phase of PI accumulation and actin polymerization is more prominent in less differentiated, unpolarized cells, is selectively increased by disruption of PTEN, and is relatively more sensitive to perturbations of PI3K. Optimal levels of the second responses allow the cell to respond rapidly to switches in gradient direction by extending lateral pseudopods. Consequently, PI3K inhibitors impair chemotaxis in wild-type cells but partially restore polarity and chemotactic response in pten- cells. Surprisingly, the fast phase of PI(3,4,5)P3 accumulation and actin polymerization, which is relatively resistant to PI3K inhibition, can support inefficient but reasonably accurate chemotaxis.

Inositol pyrophosphates mediate chemotaxis in Dictyostelium via pleckstrin homology domain-PtdIns(3,4,5)P3 interactions.

Inositol phosphates are well-known signaling molecules, whereas the inositol pyrophosphates, such as diphosphoinositol pentakisphosphate (InsP7/IP7) and bis-diphosphoinositol tetrakisphosphate (InsP8/IP8), are less well characterized. We demonstrate physiologic regulation of Dictyostelium chemotaxis by InsP7 mediated by its competition with PtdIns(3,4,5)P3 for binding pleckstrin homology (PH) domain-containing proteins. Chemoattractant stimulation triggers rapid and sustained elevations in InsP7/InsP8 levels. Depletion of InsP7 and InsP8 by deleting the gene for InsP6 kinase (InsP6K/IP6K), which converts inositol hexakisphosphate (InsP6/IP6) to InsP7, causes rapid aggregation of mutant cells and increased sensitivity to cAMP. Chemotaxis is mediated by membrane translocation of certain PH domain-containing proteins via specific binding to PtdIns(3,4,5)P3. InsP7 competes for PH domain binding with PtdIns(3,4,5)P3 both in vitro and in vivo. InsP7 depletion enhances PH domain membrane translocation and augments downstream chemotactic signaling activity.

Receptor-mediated regulation of PI3Ks confines PI(3,4,5)P3 to the leading edge of chemotaxing cells.

Recent studies have demonstrated that PH domains specific for PI(3,4,5)P3 accumulate at the leading edge of a number of migrating cells and that PI3Ks and PTEN associate with the membrane at the front and back, respectively, of chemotaxing Dictyostelium discoideum cells. However, the dependence of chemoattractant induced changes in PI(3,4,5)P3 on PI3K and PTEN activities have not been defined. We find that bulk PI(3,4,5)P3 levels increase transiently upon chemoattractant stimulation, and the changes are greater and more prolonged in pten- cells. PI3K activation increases within 5 s of chemoattractant addition and then declines to a low level of activity identically in wild-type and pten- cells. Reconstitution of the PI3K activation profile can be achieved by mixing membranes from stimulated pi3k1-/pi3k2- cells with cytosolic PI3Ks from unstimulated cells. These studies show that significant control of chemotaxis occurs upstream of the PI3Ks and that regulation of the PI3Ks and PTEN cooperate to shape the temporal and spatial localization of PI(3,4,5)P3.

Temporal and spatial regulation of chemotaxis.

The ability to sense and respond to shallow gradients of extracellular signals is remarkably similar in Dictyostelium discoideum amoebae and mammalian leukocytes. Chemoattractant receptors and G proteins are fairly evenly distributed along the cell surface. Receptor occupancy generates local excitatory and global inhibitory processes that balance to control the chemotactic response. Uniform stimuli transiently recruit PI3Ks to, and release PTEN from, the plasma membrane, while gradients of chemoattractant cause the two enzymes to bind to the membrane at the front and back of the cell, respectively. Interference with PI3Ks alters chemotaxis, and disruption of PTEN broadens PI localization and actin polymerization in parallel. Thus, counteracting signals from the upstream elements of the pathway converge to regulate the key enzymes of PI metabolism, localize these lipids, and direct pseudopod formation.