Efficacy of flossing and mouth rinsing regimens on plaque and gingivitis: a randomized clinical trial.

BACKGROUND: To investigate the effects of combinations of mechanical (brushing and flossing) and chemotherapeutic regimens which included essential oils (EO) non-alcohol and alcohol-containing mouthrinses compared to brushing only in the prevention and reduction of plaque, gingivitis, and gingival bleeding. METHODS: This was a randomized, virtually supervised, examiner blind, controlled clinical trial. Following informed consent and screening, subjects (N = 270) with gingivitis were randomly assigned to one of the following regimens: (1) Brush Only (B, n = 54); (2) Brush/Rinse (EO alcohol-containing mouthrinse) (BA, n = 54); (3) Brush/Rinse (EO non-alcohol containing mouthrinse) (BZ, n = 54); (4) Brush/Floss (BF, n = 54); (5) Brush/Floss/Rinse (EO non-alcohol containing mouthrinse) (BFZ, n = 54). Unflavored waxed dental floss (REACH unflavored waxed dental floss), and fluoridated toothpaste (Colgate Cavity Protection) were used. Examinations included oral hard and soft tissue, plaque, gingivitis, gingival bleeding, probing depth and bleeding on probing. RESULTS: After 12 weeks, both BA and BZ and the BFZ group were superior in reducing interproximal plaque (30.8%, 18.2%, 16.0%, respectively), gingivitis (39.0%, 36.9%, 36.1%, respectively), and bleeding (67.8%, 73.6%, 79.8%, respectively) compared to B. The BF group did not provide significant reductions in interproximal plaque but did reduce interproximal gingivitis (5.1%, p = 0.041) at Week 4 and bleeding at Weeks 4 and 12 (34.6%, 31.4%, p < 0.001 respectively) compared to B. The BFZ group did not significantly reduce interproximal plaque, gingivitis or bleeding compared to BZ. CONCLUSIONS: This study demonstrated that the addition of EO non-alcohol containing mouthrinse to the manual toothbrushing and flossing regimen further reduces plaque, gingivitis and bleeding showing that addition of EO mouthrinses (alcohol or non-alcohol containing) to the oral hygiene regimen provides sustained reductions in plaque to help maintain gingival health after a dental prophylaxis. Dental professional recommendation of the addition of an EO non-alcohol containing mouthrinse to daily oral hygiene routines of brushing or brushing and flossing should be considered to aid supragingival plaque control and improve gingivitis prevention. STUDY REGISTRY NUMBER: NCT05600231.

Quantitative analysis of the effects of brushing, flossing, and mouthrinsing on supragingival and subgingival plaque microbiota: 12-week clinical trial.

BACKGROUND: Translational microbiome research using next-generation DNA sequencing is challenging due to the semi-qualitative nature of relative abundance data. A novel method for quantitative analysis was applied in this 12-week clinical trial to understand the mechanical vs. chemotherapeutic actions of brushing, flossing, and mouthrinsing against the supragingival dental plaque microbiome. Enumeration of viable bacteria using vPCR was also applied on supragingival plaque for validation and on subgingival plaque to evaluate interventional effects below the gingival margin. METHODS: Subjects with gingivitis were enrolled in a single center, examiner-blind, virtually supervised, parallel group controlled clinical trial. Subjects with gingivitis were randomized into brushing only (B); brushing and flossing (BF); brushing and rinsing with Listerine® Cool Mint® Antiseptic (BA); brushing and rinsing with Listerine® Cool Mint® Zero (BZ); or brushing, flossing, and rinsing with Listerine® Cool Mint® Zero (BFZ). All subjects brushed twice daily for 1 min with a sodium monofluorophosphate toothpaste and a soft-bristled toothbrush. Subjects who flossed used unflavored waxed dental floss once daily. Subjects assigned to mouthrinses rinsed twice daily. Plaque specimens were collected at the baseline visit and after 4 and 12 weeks of intervention. Bacterial cell number quantification was achieved by adding reference amounts of DNA controls to plaque samples prior to DNA extraction, followed by shallow shotgun metagenome sequencing. RESULTS: 286 subjects completed the trial. The metagenomic data for supragingival plaque showed significant reductions in Shannon-Weaver diversity, species richness, and total and categorical bacterial abundances (commensal, gingivitis, and malodor) after 4 and 12 weeks for the BA, BZ, and BFZ groups compared to the B group, while no significant differences were observed between the B and BF groups. Supragingival plaque vPCR further validated these results, and subgingival plaque vPCR demonstrated significant efficacy for the BFZ intervention only. CONCLUSIONS: This publication reports on a successful application of a quantitative method of microbiome analysis in a clinical trial demonstrating the sustained and superior efficacy of essential oil mouthrinses at controlling dental plaque compared to mechanical methods. The quantitative microbiological data in this trial also reinforce the safety and mechanism of action of EO mouthrinses against plaque microbial ecology and highlights the importance of elevating EO mouthrinsing as an integral part of an oral hygiene regimen. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov on 31/10/2022. The registration number is NCT05600231.

Quantitative analysis of the effects of essential oil mouthrinses on clinical plaque microbiome: a parallel-group, randomized trial.

BACKGROUND: The rich diversity of microorganisms in the oral cavity plays an important role in the maintenance of oral health and development of detrimental oral health conditions. Beyond commonly used qualitative microbiome metrics, such as relative proportions or diversity, both the species-level identification and quantification of bacteria are key to understanding clinical disease associations. This study reports the first-time application of an absolute quantitative microbiome analysis using spiked DNA standards and shotgun metagenome sequencing to assess the efficacy and safety of product intervention on dental plaque microbiome. METHODS: In this parallel-group, randomized clinical trial, essential oil mouthrinses, including LISTERINE® Cool Mint Antiseptic (LCM), an alcohol-containing prototype mouthrinse (ACPM), and an alcohol-free prototype mouthrinse (AFPM), were compared against a hydroalcohol control rinse on clinical parameters and the oral microbiome of subjects with moderate gingivitis. To enable a sensitive and clinically meaningful measure of bacterial abundances, species were categorized according to their associations with oral conditions based on published literature and quantified using known amounts of spiked DNA standards. RESULTS: Multivariate analysis showed that both LCM and ACPM shifted the dysbiotic microbiome composition of subjects with gingivitis to a healthier state after 4 weeks of twice-daily use, resembling the composition of subjects with clinically healthy oral conditions recruited for observational reference comparison at baseline. The essential oil-containing mouthrinses evaluated in this study showed statistically significant reductions in clinical gingivitis and plaque measurements when compared to the hydroalcohol control rinse after 6 weeks of use. CONCLUSIONS: By establishing a novel quantitative method for microbiome analysis, this study sheds light on the mechanisms of LCM mouthrinse efficacy on oral microbial ecology, demonstrating that repeated usage non-selectively resets a gingivitis-like oral microbiome toward that of a healthy oral cavity. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov on 10/06/2021. The registration number is NCT04921371.

In vitro antimicrobial effects of chlorhexidine diacetate versus chlorhexidine free base dressings.

OBJECTIVE: The aim of this study was to investigate the in vitro antimicrobial performance of a chlorhexidine diacetate dressing and a chlorhexidine free base dressing to determine if the free base form of chlorhexidine has the potential to be an effective alternative to the chlorhexidine salts used in conventional, chlorhexidine-based antimicrobial dressings. METHOD: Dressing samples were inoculated with clinically relevant pathogenic microorganisms including Gram-positive and Gram-negative bacteria, yeasts and fungus, and subsequently evaluated for in vitro log10 reduction at 1-, 3-, and 7-day time points. Chlorhexidine mole content was also calculated as a function of dressing surface area for both sample types to allow for formulation-independent comparison between the dressings. RESULTS: The chlorhexidine free base dressing demonstrated >0.5 log10 superior mean antimicrobial efficacy at 67% of the experimental time points and equivalent mean antimicrobial efficacy (≤0.5 log10 different) at the remaining time points when compared with the chlorhexidine diacetate dressing. The chlorhexidine free base dressing was also found to contain 36% less chlorhexidine mole content than the chlorhexidine diacetate dressing. CONCLUSION: Our results suggest that a dressing formulated with chlorhexidine free base can deliver in vitro antimicrobial performance at both a magnitude and rate that meets or exceeds that of a chlorhexidine diacetate-based dressing, while also allowing for a reduction in total chlorhexidine content per dressing. These findings could be of particular interest to researchers developing new antimicrobial technologies as well as to infection preventionists when evaluating antimicrobial products for use on clinical patients at elevated risk of infection.

Comparison of two pixelated insoles using in-shoe pressure sensors to determine percent offloading: case studies.

OBJECTIVE: The gold standard for offloading neuropathic forefoot and midfoot wounds is the total contact cast (TCC). However, in practice TCC is rarely used and is contraindicated in patients with fluctuating oedema, poor perfusion, lack of adequate tissue oxygenation and morbid obesity. It can also be too restrictive for patients, inevitably resulting in treatment rejection and delayed healing. This paper examines the role of shoe-based offloading devices as an alternative in reducing plantar pressure and optimising the healing of neuropathic ulcers. METHOD: Healthy subjects were recruited and fitted for two types of pixelated insoles: PegAssist (PA) insole system (Darco International, US) and FORS-15 (FORS) offloading insole (Saluber, Italy). An area of discreet, elevated high pressure was created by adding a 1/4-inch-thick felt pad to the plantar skin under the first metatarsal head. Subjects walked barefoot in surgical shoes with standard insoles (Condition 1), barefoot in pixelated insoles (Condition 2), barefoot with pixels removed (Condition 3). Dynamic plantar pressures were measured using F-Scan and the results were analysed to determine plantar pressure changes in each condition. RESULTS: Using PA, the percentage reduction of plantar pressure (kPa) under the first metatarsal between Condition 1 and Condition 2 was 10.54±15.81% (p=0.022), between Condition 2 and Condition 3 was 40.13±11.11% (p<0.001), and between Condition 1 and Condition 3 was 46.67±12.95 % (p<0.001). Using FORS, the percentage reduction between Condition 1 and Condition 2 was 24.25±23.33% (p=0.0029), between Condition 2 and Condition 3 was 23.61±19.45% (p<0.001), and between Condition 1 and Condition 3 was 43.39±18.70% (p<0.001). A notable difference in the findings between the two insoles was the presence of a significant edge effect associated with PA, indicating that the offloading was not entirely successful. No edge effect was detected with FORS. CONCLUSION: Our current analysis shows that pixelated insoles exhibit potential for supplemental offloading in surgical shoes. These devices could provide an alternative way for physicians to offload plantar wounds and expedite closure for patients that cannot tolerate a TCC or other restrictive devices.

α-Helix or ß-Turn? An Investigation into N-Terminally Constrained Analogues of Glucagon-like Peptide 1 (GLP-1) and Exendin-4.

Peptide agonists acting on the glucagon-like peptide 1 receptor (GLP-1R) promote glucose-dependent insulin release and therefore represent important therapeutic agents for type 2 diabetes (T2D). Previous data indicated that an N-terminal type II ß-turn motif might be an important feature for agonists acting on the GLP-1R. In contrast, recent publications reporting the structure of the full-length GLP-1R have shown the N-terminus of receptor-bound agonists in an α-helical conformation. To reconcile these conflicting results, we prepared N-terminally constrained analogues of glucagon-like peptide 1 (GLP-1) and exendin-4 and evaluated their receptor affinity and functionality in vitro; we then examined their crystal structures in complex with the extracellular domain of the GLP-1R and used molecular modeling and molecular dynamics simulations for further investigations. We report that the peptides' N-termini in all determined crystal structures adopted a type II ß-turn conformation, but in vitro potency varied several thousand-fold across the series. Potency correlated better with α-helicity in our computational model, although we have found that the energy barrier between the two mentioned conformations is low in our most potent analogues and the flexibility of the N-terminus is highlighted by the dynamics simulations.

The effects of essential oil mouthrinses with or without alcohol on plaque and gingivitis: a randomized controlled clinical study.

BACKGROUND: The efficacy of several variants of essential oil mouthrinses has been studied extensively. This is the first study to compare the anti-plaque and anti-gingivitis efficacy of two marketed essential oil mouthrinses: one is an alcohol containing mouthrinse and the other one is an alcohol-free mouthrinse. METHODS: This examiner-blind, parallel-group study randomized subjects to three groups: 1) Mechanical Oral Hygiene (MOH) only; 2) MOH plus Alcohol-Containing essential oil Mouthrinse (ACM); 3) MOH plus Alcohol-Free essential oil Mouthrinse (AFM). Primary endpoint was whole-mouth mean Modified Gingival Index (MGI) at six months. Secondary endpoints included whole-mouth mean MGI at one and three months, and whole-mouth mean Plaque Index (PI) and whole-mouth mean Bleeding Index (BI) at one, three and six months. Safety assessments were conducted at all time points. RESULTS: A total of 370 subjects were enrolled; 348 subjects completed the study. After six months, subjects using essential oil mouthrinses with or without alcohol showed significant reduction (p < 0.001) in gingivitis (28.2% and 26.7%, respectively) and significant reduction (p < 0.001) in plaque (37.8% and 37.0%, respectively), compared to those performing MOH only. Significant reductions in MGI, PI, and BI (p < 0.001) were observed at one and three months and also at six months for mean BI. No statistically significant differences were observed for all measured indices between ACM and AFM groups at any time point. Both mouthrinses were well tolerated. CONCLUSIONS: No significant differences were observed in the efficacy of ACM and AFM to reduce plaque and gingivitis, when used in addition to MOH, over six months. TRIAL REGISTRATION: The trial was registered on clinicaltrials.gov on November 30, 2016. The registration number is NCT02980497 .

N-glycosylation proteome enrichment analysis in kidney reveals differences between diabetic mouse models.

BACKGROUND: Diabetic nephropathy (DN) is a late complication in both type 1 diabetes mellitus (T1DM) and T2DM. Already at an early stage of DN morphological changes occur at the cell surface and in the extracellular matrix where the majority of the proteins carry N-linked glycosylations. These glycosylated proteins are highly important in cell adhesion and cell-matrix processes but not much is known about how they change in DN or whether the distinct etiology of T1DM and T2DM could have an effect on their abundances. METHOD: We enriched for the N-glycosylated kidney proteome in db/db mice dosed with insulin or vehicle, in streptozotocin-induced (STZ) diabetic mice and healthy control mice dosed with vehicle. Glycopeptides were analyzed with label-free shotgun mass spectrometry and differential protein abundances identified in both mouse models were compared using multivariate analyses. RESULTS: The majority of the N-glycosylated proteins were similarly regulated in both mouse models. However, distinct differences between the two mouse models were for example seen for integrin-ß1, a protein expressed mainly in the glomeruli which abundance was increased in the STZ diabetic mice while decreased in the db/db mice and for the sodium/glucose cotransporter-1, mainly expressed in the proximal tubules which abundance was increased in the db/db mice but decreased in the STZ diabetic mice. Insulin had an effect on the level of both glomerular and tubular proteins in the db/db mice. It decreased the abundance of G-protein coupled receptor-116 and of tyrosine-protein phosphatase non-receptor type substrate-1 away from the level in the healthy control mice. CONCLUSIONS: Our finding of differences in the N-glycosylation protein profiles in the db/db and STZ mouse models suggest that the etiology of DN could give rise to variations in the cell adhesion and cell-matrix composition in T1DM and T2DM. Thus, N-glycosylated protein differences could be a clue to dissimilarities in T1DM and T2DM at later stages of DN. Furthermore, we observed insulin specific regulation of N-glycosylated proteins both in the direction of and away from the abundances in healthy control mice.

US Veterans' Court Programs: An Inventory and Analysis of National Survey Data.

This study used data from a phone survey inventory of US veterans' courts to provide descriptive information on the current status of their various elements. To identify which items were most predictive of a court's percentage of subjects terminated from their program, a linear regression was performed. The following were associated with higher rates of termination from the veterans' court (VC) program: (a) programs that offered phase progression based on measurable goals, (b) programs that conduct frequent drug and alcohol testing, and (c) programs for which sanctions are more severe for failing immediate goals (sobriety) versus long-term ones (completion of training). The following were associated with lower rates of termination from the VC program: (a) programs in which later phases permit less stringent testing, (b) programs utilizing behavioral contracts, (c) programs utilizing brief incarcerations. This inventory provides nationwide empirical data that may be used in the development of veterans' courts.

Safe, long-term management of bioburden that helps promote healing Evidence review of DACC technology.

Unlike common antimicrobial dressings, the Cutimed Sorbact range does not kill pathogens, but instead binds them to its surface, so they can be safely removed at dressing change. As a result, it can be used long term with minimal risk of side effects. This supplement describes the evidence base on the efficacy of DACC technology.

In vitro and clinical experience of Cutimed Sorbact: the evidence base.

In the previous chapter, Keith Cutting and James McGuire explored the link between infection and wound chronicity and explained how Cutimed Sorbact can be used to promote healing in chronic wounds. The following sections summarise the existing evidence for the Cutimed Sorbact range of dressings.

Offending outcomes of a mental health youth diversion pilot scheme in England.

BACKGROUND: A youth justice diversion scheme designed to enhance health provision for young people with mental health and developmental problems as soon as they enter the youth justice system has been piloted in six areas of England. AIM: As part of a wider evaluation of the first youth justice diversion scheme outside the USA, our aim here was to examine re-offending. We sought to test the hypothesis that a specialised service for young people with mental health difficulties would be associated with reductions in re-offending. In addition, we examined factors associated with the re-offending that occurred. METHODS: Two hundred and eight young offenders with access to the diversion scheme and 200 without were compared in four geographical area pairings to allow for socio-demographic contextual differences. Officially recorded re-offending was ascertained for 15-30 months after study entry. We also tested characteristics associated with re-offending among everyone entering the diversion scheme (n = 870). RESULTS: There was no statistically significant difference in re-offending rates between the diversion and comparison samples, but those with access to diversion had significantly longer periods of desistance from offending than those who did not. In multivariate analysis, the only significant characteristic associated with re-offending was history of previous offending. CONCLUSIONS: Prevention of re-offending is only one of the potentially beneficial outcomes of diversion of young people who are vulnerable because of mental health problems, but it is an important one. The advantage of longer survival without prevention of re-offending suggests that future research should explore critical timings for these young people. The equivocal nature of the findings suggests that a randomised controlled trial would be justified.

Moving upstream: why rehabilitative justice in military discharge proceedings serves a public health interest.

The cultural divide between US military and civilian institutions amplifies the consequences of military discharge status on public health and criminal justice systems in a manner that is invisible to a larger society. Prompt removal of problematic wounded warriors through retributive justice is more expedient than lengthy mental health treatment. Administrative and punitive discharges usually preclude Department of Veterans Affairs eligibility, posing a heavy public health burden. Moving upstream--through military rehabilitative justice addressing military offenders' mental health needs before discharge--will reduce the downstream consequences of civilian maladjustment and intergenerational transmission of mental illness. The public health community can play an illuminating role by gathering data about community effect and by advocating for policy change at Department of Veterans Affairs and community levels.

Characterization of membrane-shed microvesicles from cytokine-stimulated ß-cells using proteomics strategies.

Microparticles and exosomes are two of the most well characterized membrane-derived microvesicles released either directly from the plasma membrane or released through the fusion of intracellular multivesicular bodies with the plasma membrane, respectively. They are thought to be involved in many significant biological processes such as cell to cell communication, rescue from apoptosis, and immunological responses. Here we report for the first time a quantitative study of proteins from ß-cell-derived microvesicles generated after cytokine induced apoptosis using stable isotope labeled amino acids in cell culture combined with mass spectrometry. We identified and quantified a large number of ß-cell-specific proteins and proteins previously described in microvesicles from other cell types in addition to new proteins located to these vesicles. In addition, we quantified specific sites of protein phosphorylation and N-linked sialylation in proteins associated with microvesicles from ß-cells. Using pathway analysis software, we were able to map the most distinctive changes between microvesicles generated during growth and after cytokine stimulation to several cell death and cell signaling molecules including tumor necrosis factor receptor superfamily member 1A, tumor necrosis factor, α-induced protein 3, tumor necrosis factor-interacting kinase receptor-interacting serine-threonine kinase 1, and intercellular adhesion molecule 1.

A comparison of two total contact cast constructs with variable body mass.

OBJECTIVE: There is a growing body of evidence implicating obesity as having a negative effect on the development and treatment of diabetic foot disease. The aim of this study was to increase the body of knowledge on the effects of obesity on foot function, specifically as it relates to peak plantar pressures in the total contact cast (TCC). Our investigational objectives were to compare the effect of two different TCC designs on mean peak plantar pressures, and to evaluate the efficacy of two TCC constructs with increasing body mass. METHOD: The primary outcome measure was mean peak plantar pressure in the heel, midfoot, forefoot and first metatarsal as measured with an in-shoe pressure measurement system. The variables were patient weight (from 'normal' body mass index (BMI) to 'overweight', 'obese' and 'morbidly obese') and the TCC construct (with both a standard and alternate cast design). The standard TCC is considered the gold standard for off-loading of the diabetic foot. The alternate TCC was designed to use the essential offloading component of the traditional TCC, namely the total contact leg section, with use of an open cell polyurethane foam to transfer load from the foot to the lower leg, thereby offloading the foot by suspending it within a padded fiberglass walking cast. RESULTS: We did not observe statistically significant differences in mean peak plantar pressures in any plantar foot anatomic area or with any body mass between the two TCC designs. CONCLUSION: Based on the results, we concluded that the alternate TCC design provides another viable TCC construct option for practitioners working with the neuropathic foot. This investigation also provides specific data on changes that occur in peak plantar pressures with use of the total contact cast and variable BMIs. DECLARATION OF INTEREST: none.

The use of PriMatrix, a fetal bovine acellular dermal matrix, in healing chronic diabetic foot ulcers: a prospective multicenter study.

OBJECTIVE: The objective of this multicenter study was to prospectively evaluate the healing outcomes of chronic diabetic foot ulcers (DFUs) treated with PriMatrix (TEI Biosciences, Boston, Massachusetts), a fetal bovine acellular dermal matrix. METHODS: Inclusion criteria required the subjects to have a chronic DFU that ranged in area from 1 to 20 cm² and failed to heal more than 30% during a 2-week screening period when treated with moist wound therapy. For qualifying subjects, PriMatrix was secured into a clean, sharply debrided wound; dressings were applied to maintain a moist wound environment, and the DFU was pressure off-loaded. Wound area measurements were taken weekly for up to 12 weeks, and PriMatrix was reapplied at the discretion of the treating physician. RESULTS: A total of 55 subjects were enrolled at 9 US centers with 46 subjects progressing to study completion. Ulcers had been in existence for an average of 286 days, and initial mean ulcer area was 4.34 cm². Of the subjects completing the study, 76% healed by 12 weeks with a mean time to healing of 53.1 ± 21.9 days. The mean number of applications for these healed wounds was 2.0 ± 1.4, with 59.1% healing with a single application of PriMatrix and 22.9% healing with 2 applications. For subjects not healed by 12 weeks, the average wound area reduction was 71.4%. CONCLUSION: The results of this multicenter prospective study demonstrate that the use of PriMatrix integrated with standard-of-care therapy is a successful treatment regimen to heal DFUs.

Effect of variable body mass on plantar foot pressure and off-loading device efficacy.

An increasing body of evidence has implicated obesity as having a negative effect on the development, treatment, and outcome of lower extremity pathologic entities, including diabetic foot disease. The objective of the present study was to increase the body of knowledge with respect to the effects of obesity on foot function. Specifically, we attempted to (1) describe the relationship between an increasing body mass index (BMI) on plantar foot pressures during gait, and (2) evaluate the efficacy of commonly prescribed off-loading devices with an increasing BMI. A repeated measures design was used to compare the peak plantar foot pressures under multiple test conditions, with the volunteers acting as their own controls. The primary outcome measure was the mean peak plantar pressure in the heel, midfoot, forefoot, and first metatarsal, and the 2 variables were modification of patient weight (from "normal" BMI to "overweight," "obese," and "morbidly obese") and footwear (from an athletic sneaker to a surgical shoe, controlled ankle motion walker, and total contact cast). Statistically significant increases in the peak plantar pressures were observed with increasing volunteer BMI weight class, regardless of the off-loading device used. The present investigation has provided unique and specific data with respect to the changes that occur in the peak plantar pressures with variable BMIs across different anatomic levels and with commonly used off-loading devices. From our results, we have concluded that although the plantar pressures increase with increasing weight, it appears that at least some reduction in pressure can be achieved with an off-loading device, most effectively with the total contact cast, regardless of the patient's BMI.

Homelessness in a national sample of incarcerated veterans in state and federal prisons.

The Veterans Health Administration (VHA) has been increasing efforts to reach out to assist incarcerated veterans. While previous studies have shown strong associations between incarceration and homelessness, few studies have examined distinctive characteristics of incarcerated homeless and non-homeless veterans. National administrative data on 30,348 incarcerated veterans served by the Health Care for Re-entry Veterans (HCRV) program were analyzed. Incarcerated veterans were classified into four groups based on their history of past homelessness: not homeless, transiently homeless, episodically homeless, and chronically homeless. Multinomial logistic regression was used to compare groups on sociodemographic characteristics, criminal justice status, clinical status, and their interest in using VHA services. Of the sample, 70 % were classified as not homeless, 8 % as transiently homeless, 11 % as episodically homeless, and 11 % as chronically homeless. Thus, 30 % of the sample had a homeless history, which is five times the 6 % rate of past homelessness among adult men in the general population. Compared to non-homeless incarcerated veterans, all three homeless groups reported significantly more mental health problems, more substance abuse, more times arrested in their lifetime, more likely to be incarcerated for a non-violent offense, and were more interested in receiving VHA services after release from prison. Together, these findings suggest re-entry programs, like HCRV, can address relevant mental health-related service needs, especially among formerly homeless veterans and veterans in need of services are receptive to the offer of assistance.

Small molecule structure correctors abolish detrimental effects of apolipoprotein E4 in cultured neurons.

Apolipoprotein E4 (apoE4), the major genetic risk factor for late onset Alzheimer disease, assumes a pathological conformation, intramolecular domain interaction. ApoE4 domain interaction mediates the detrimental effects of apoE4, including decreased mitochondrial cytochrome c oxidase subunit 1 levels, reduced mitochondrial motility, and reduced neurite outgrowth in vitro. Mutant apoE4 (apoE4-R61T) lacks domain interaction, behaves like apoE3, and does not cause detrimental effects. To identify small molecules that inhibit domain interaction (i.e. structure correctors) and reverse the apoE4 detrimental effects, we established a high throughput cell-based FRET primary assay that determines apoE4 domain interaction and secondary cell- and function-based assays. Screening a ChemBridge library with the FRET assay identified CB9032258 (a phthalazinone derivative), which inhibits domain interaction in neuronal cells. In secondary functional assays, CB9032258 restored mitochondrial cytochrome c oxidase subunit 1 levels and rescued impairments of mitochondrial motility and neurite outgrowth in apoE4-expressing neuronal cells. These benefits were apoE4-specific and dose-dependent. Modifying CB9032258 yielded well defined structure-activity relationships and more active compounds with enhanced potencies in the FRET assay (IC(50) of 23 and 116 nm, respectively). These compounds efficiently restored functional activities of apoE4-expressing cells in secondary assays. An EPR binding assay showed that the apoE4 structure correction resulted from direct interaction of a phthalazinone. With these data, a six-feature pharmacophore model was constructed for future drug design. Our results serve as a proof of concept that pharmacological intervention with apoE4 structure correctors negates apoE4 detrimental effects in neuronal cells and could be further developed as an Alzheimer disease therapeutic.