Benchmarking for healthy food stores: protocol for a randomised controlled trial with remote Aboriginal and Torres Strait Islander communities in Australia to enhance adoption of health-enabling store policy and practice.

BACKGROUND: Aboriginal and Torres Strait Islander communities in remote Australia have initiated bold policies for health-enabling stores. Benchmarking, a data-driven and facilitated 'audit and feedback' with action planning process, provides a potential strategy to strengthen and scale health-enabling best-practice adoption by remote community store directors/owners. We aim to co-design a benchmarking model with five partner organisations and test its effectiveness with Aboriginal and Torres Strait Islander community stores in remote Australia. METHODS: Study design is a pragmatic randomised controlled trial with consenting eligible stores (located in very remote Northern Territory (NT) of Australia, primary grocery store for an Aboriginal community, and serviced by a Nutrition Practitioner with a study partner organisation). The Benchmarking model is informed by research evidence, purpose-built best-practice audit and feedback tools, and co-designed with partner organisation and community representatives. The intervention comprises two full benchmarking cycles (one per year, 2022/23 and 2023/24) of assessment, feedback, action planning and action implementation. Assessment of stores includes i adoption status of 21 evidence-and industry-informed health-enabling policies for remote stores, ii implementation of health-enabling best-practice using a purpose-built Store Scout App, iii price of a standardised healthy diet using the Aboriginal and Torres Strait Islander Healthy Diets ASAP protocol; and, iv healthiness of food purchasing using sales data indicators. Partner organisations feedback reports and co-design action plans with stores. Control stores receive assessments and continue with usual retail practice. All stores provide weekly electronic sales data to assess the primary outcome, change in free sugars (g) to energy (MJ) from all food and drinks purchased, baseline (July-December 2021) vs July-December 2023. DISCUSSION: We hypothesise that the benchmarking intervention can improve the adoption of health-enabling store policy and practice and reduce sales of unhealthy foods and drinks in remote community stores of Australia. This innovative research with remote Aboriginal and Torres Strait Islander communities can inform effective implementation strategies for healthy food retail more broadly. TRIAL REGISTRATION: ACTRN12622000596707, Protocol version 1.

Development of UPLC-UV-ELSD Method for Fatty Acid Profiling in Polysorbate 80 and Confirmation of the Presence of Conjugated Fatty Acids by Mass Spectrometry, UV Absorbance and Proton Nuclear Magnetic Resonance Spectroscopy.

Polysorbate 80 (PS80), a chemical substance composed of sorbitol, ethylene glycol, and fatty acids, is commonly used in pharmaceutical drug products to stabilize formulations. However, recent studies have demonstrated that PS80 may hydrolyze over time and the released free fatty acids (FFAs) may lead to particle formation. Naming conventions of fatty acids in current pharmacopeia and in products' certificates of analysis (CoA) of PS80 do not typically distinguish between isomeric species of fatty acids in PS80. Thus, methods to fully characterize the fatty acid species present in PS80 raw materials are needed to enhance quality control strategies of pharmaceuticals using PS80. Here, extended effort is taken to characterize fatty acids in hydrolyzed PS80 raw materials and elucidate the identities of isomeric fatty acid species. In this work, a method was developed and optimized for separation and detection of fatty acids in alkaline hydrolyzed PS80 raw materials using ultra performance liquid chromatography (UPLC) with ultra-violet (UV) detection and evaporative light scattering detection (ELSD). Fatty acids not specified in the current pharmacopeias were detected in PS80 raw material by the developed LC-UV-ELSD method including conjugated forms of linoleic and linolenic fatty acid species. Their identities were orthogonally confirmed by retention time agreement with analytical standards, accurate mass by high resolution mass spectrometry, UV absorbance, and proton nuclear magnetic resonance spectroscopy. The detected conjugated fatty acids are theoretically more hydrophobic and less soluble than their unconjugated counterparts and may increase the propensity of PS80 to form particles upon hydrolysis. This work highlights the need for better quality control of PS80 raw material, as it may eventually play a critical role in product quality of therapeutic proteins.

Injury Pattern in Ligamentous Lisfranc Injuries in Competitive Athletes.

BACKGROUND:: We report data on the largest cohort to date of patients who sustained a ligamentous Lisfranc injury during sport. To date, the prevalence of concurrent intercuneiform ligament injuries in the competitive athlete with subtle Lisfranc instability has not been reported. METHODS:: Eighty-two patients (64 males, 18 females) sustained an unstable Lisfranc injury (49 left, 33 right) and met inclusion criteria. Injuries were classified as traditional dislocation (TRAD, first to second TMT ligament tear), medial column dislocation (MCD, second TMT, and medial-middle cuneiform ligament tear), or proximal extension dislocation (PE, first, second, and medial-middle cuneiform ligament tear) and the injury pattern confirmed at surgery. All athletes underwent open reduction with internal fixation (ORIF) of each unstable midfoot segment. Fisher exact tests and 2-tailed t tests were used to analyze statistical significance according to injury pattern, sport, gender difference, hindfoot angle alignment, and injured side ( P < .05). RESULTS:: Average age of athletes was 21.0 ± 5.3 years old (range 12-40), and return to sports was 7.5 ± 2.1 months. Injury distribution was as follows: TRAD (n = 40), MCD (n = 17), and PE (n = 23). MCD trended toward a longer return to sport (8.4 ± 3.3 months, P = .074). Football was the most common sport at time of injury (n = 48). Wakeboard athletes (n = 5) were older (31.4 ± 3.2, P = .0002), and MCD tears were more prevalent among them ( P = .061). Basketball (n = 13) players were significantly younger (19.1 ± 2.5 years, P = .028) and returned to sports quicker (5.2 ± 0.7, P = .0002). Return to sport data indicated a typical population for athletes with Lisfranc injury in these sports. CONCLUSION:: Proximal extension disruption (intercuneiform ligament tear) occurred in 50% of these low-energy Lisfranc athletic injuries. MCD and PE may be more prevalent than previously understood. This is the first study to document the extent, pattern, and prevalence of associated intercuneiform ligament tears in the competitive athlete with a low-energy subtle, unstable Lisfranc injury. LEVEL OF EVIDENCE:: Level IV, retrospective case series.

Pancreatic Cancer-Associated Depression: A Case Report and Review of the Literature.

The prevalence of major depressive disorder (MDD) in pancreatic cancer (PC) has been reported up to 7 times higher than the general population. Despite repeated studies that show worse quality of life, survival outcomes, and treatment compliance in cancer patients with depression, baseline antidepressant use ranges from 15% to 27%. A meta-analysis of 6 prospective trials specific to PC estimates that 43% of patients with PC experience depression after diagnosis. This is especially alarming in patients with PC, who may experience a prodrome of symptoms including depression and loss of drive. In fact, this prodrome of symptoms may very well be due to an overexpression of indoleamine 2,3-dioxgenase, an enzyme in the kynurenine pathway that leads to serotonin depletion and the buildup of cytotoxic metabolites in the brain. In this literature review, we outline all previous studies pertinent to PC and depression, as well as the molecular underpinnings that may contribute to states of depression, and report on previous randomized control trials in cancer populations that investigate the use of antidepressants to treat depressive symptoms and improve quality of life both prophylactically and after the onset of major depressive disorder. In addition, we detail a case report outlining the precipitous decline in health in 1 patient with PC and depression.

Development of the good food planning tool: A food system approach to food security in indigenous Australian remote communities.

Few frameworks exist to assist food system planning, especially for Indigenous Australian remote communities. We developed a Good Food Planning Tool to support stakeholders to collectively plan and take action for local food system improvement. Development occurred over a four-year period through an evolving four phase participatory process that included literature review, several meetings with representatives of various organisations and communities and application of the Tool with multi-sector groups in each of four Indigenous Australian remote communities. A diverse range of 148 stakeholders, 78 of whom were Indigenous, had input to its development. Five food system domains: (i) Leadership and partnerships; (ii) Traditional food and local food production; (iii) Food businesses; (iv) Buildings, public places and transport; (v) Community and services and 28 activity areas form the framework of the Tool. The Good Food Planning Tool provides a useful framework to facilitate collective appraisal of the food system and to identify opportunities for food system improvement in Indigenous Australian remote communities, with potential for adaptation for wider application.

Isolating and using sections of bovine mesenteric artery and vein as a bioassay to test for vasoactivity in the small intestine.

Mammalian gastrointestinal systems are constantly exposed to compounds (desirable and undesirable) that can have an effect on blood flow to and from that system. Changes in blood flow to the small intestine can result in effects on the absorptive functions of the organ. Particular interest in toxins liberated from feedstuffs through fermentative and digestive processes has developed in ruminants as an area where productive efficiencies could be improved. The video associated with this article describes an in vitro bioassay developed to screen compounds for vasoactivity in isolated cross-sections of bovine mesenteric artery and vein using a multimyograph. Once the blood vessels are mounted and equilibrated in the myograph, the bioassay itself can be used: as a screening tool to evaluate the contractile response or vasoactivity of compounds of interest; determine the presence of receptor types by pharmacologically targeting receptors with specific agonists; determine the role of a receptor with the presence of one or more antagonists; or determine potential interactions of compounds of interest with antagonists. Through all of this, data are collected real-time, tissue collected from a single animal can be exposed to a large number of different experimental treatments (an in vitro advantage), and represents vasculature on either side of the capillary bed to provide an accurate picture of what could be happening in the afferent and efferent blood supply supporting the small intestine.

Optimal management of ankle syndesmosis injuries.

Syndesmosis injuries occur when there is a disruption of the distal attachment of the tibia and fibula. These injuries occur commonly (up to 18% of ankle sprains), and the incidence increases in the setting of athletic activity. Recognition of these injuries is key to preventing long-term morbidity. Diagnosis and treatment of these injuries requires a thorough understanding of the normal anatomy and the role it plays in the stability of the ankle. A complete history and physical examination is of paramount importance. Patients usually experience an external rotation mechanism of injury. Key physical exam features include detailed documentation about areas of focal tenderness (syndesmosis and deltoid) and provocative maneuvers such as the external rotation stress test. Imaging workup in all cases should consist of radiographs with the physiologic stress of weight bearing. If these images are inconclusive, then further imaging with external rotation stress testing or magnetic resonance imaging are warranted. Nonoperative treatment is appropriate for stable injuries. Unstable injuries should be treated operatively. This consists of stabilizing the syndesmosis with either trans-syndesmotic screw or tightrope fixation. In the setting of a concomitant Weber B or C fracture, the fibula is anatomically reduced and stabilized with a standard plate and screw construct. Proximal fibular fractures, as seen in the Maisonneuve fracture pattern, are not repaired operatively. Recent interest is moving toward repair of the deltoid ligament, which may provide increased stability, especially in rehabilitation protocols that involve early weight bearing. Rehabilitation is focused on allowing patients to return to their pre-injury activities as quickly and safely as possible. Protocols initially focus on controlling swelling and recovery from surgery. The protocols then progress to restoration of motion, early protected weight bearing, restoration of strength, and eventually a functional progression back to desired activities.

Acute achilles tendon repair: strength outcomes after an acute bout of exercise in recreational athletes.

BACKGROUND: This is the first study to evaluate the effect of an acute bout of exercise on strength evaluation after Achilles tendon (AT) rupture and repair. METHODS: Forty patients sustained an acute AT injury and met inclusion criteria for this study. At a minimum of 12 months after operative repair, patients were measured for (1) calf circumference, (2) bilateral isokinetic strength on a Cybex dynamometer before and after 30 minutes of walking at 70% maximal exertion, and (3) subjective evaluation by AAOS lower limb core and foot and ankle modules. Follow-up occurred at a mean of 32.4 ± 20.7 (range, 12-80) months after surgery, and patients were on average 44.4 ± 8.6 (range, 20-62) years old. One-tailed Student's paired t tests analyzed significance for strength and fatigue between the involved and uninvolved ankle (P < .05). RESULTS: The calf circumference of the involved ankle was significantly smaller than the uninvolved ankle by 1.9 cm, or 4.7%. Plantarflexion deficits of the involved ankle ranged from 12% to 18% for peak torque (P < .0001) and from 17% to 25% for work per repetition (P < .0001), but both ankles fatigued at equal proportions as measured after exercise. Dorsiflexion strength of the involved ankle increased 6% to 11% for peak torque (P = .070) and 1% to 25% for peak work (P = .386). Reported AAOS lower limb core and foot and ankle scores averaged 99.8 and 96.0, respectively. CONCLUSION: After an AT rupture with repair, patients had less plantarflexion strength, and equal dorsiflexion strength in the operative leg compared to the uninvolved, normal leg. However, subjective results indicated near normal pain and function despite mild plantarflexion strength deficits. Dorsiflexion strength was normal after repair and remained normal even after an acute bout of exercise. Plantarflexion strength ratios postexercise remained similar to pre-exercise after acute exercise bouts. Athletes reported a "flat tire" feeling while running, which suggests a probable gait adjustment as cause for long-term plantarflexion strength deficits. LEVEL OF EVIDENCE: Level III, cohort study.

Evaluation of Joint Space Width and Narrowing After Isolated Partial Medial Meniscectomy for Degenerative Medial Meniscus Tears.

BACKGROUND: Few studies have evaluated the effect of existing articular cartilage damage and sex on joint space measurements after isolated degenerative medial meniscus tears. PURPOSE: To determine what factors affected joint space width and narrowing in patients after removal of isolated degenerative medial meniscus tears. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 62 patients (15 women and 47 men) with all ligaments intact, no previous surgery to either knee, and an isolated degenerative medial meniscus tear removed in 1 knee were examined. The mean age at examination was 58.2 years at a mean follow-up of 9.4 years (range, 4-20 years). Subjective results were obtained with the International Knee Documentation Committee (IKDC) knee survey. Radiographs were taken using 45° weightbearing posteroanterior views. Midpoint and perceived minimum joint space width of the medial and lateral compartments of both knees were measured to the nearest 0.1 mm by 2 observers at different times, and they were blinded as to the previous measurements (Pearson intra- and interclass correlations, >0.93). Joint space narrowing was found by calculating the difference in joint space width between knees. Percentage of normal joint space loss was calculated by dividing joint space narrowing by the joint space width in the contralateral knee. Other factors considered were patient sex and Outerbridge grading of articular cartilage. RESULTS: Women had a mean 1.5 mm less normal joint space width than men in the involved and noninvolved knees (P < .01). Mean joint space narrowing was 0.7 mm for both measurements. The mean ± standard deviation narrowing was 0.4 ± 1.2 mm for patients with grade 0-2 damage and 1.1 ± 1.3 for patients with grade 3-4 damage (P = .04). Five women (33%) and 3 men (6%) had narrowing of >50% of the normal joint space as measured in the noninjured knee (P = .016). The mean IKDC total score was 66.1 points for women, which was statistically significantly lower than the mean of 82.7 points for men (P < .01). CONCLUSION: Patients undergoing partial medial meniscectomy have greater joint space narrowing and lower subjective scores after surgery if they also have existing Outerbridge grade 3-4 damage. Women have less normal joint space than men, and more women than men experience >50% joint space narrowing after surgery.

Correlation of a single assessment numeric evaluation (SANE) rating with modified Cincinnati knee rating system and IKDC subjective total scores for patients after ACL reconstruction or knee arthroscopy.

BACKGROUND: Limited studies exist regarding how well a single assessment numeric evaluation (SANE) rating correlates with validated knee surveys. PURPOSE: To determine whether a SANE rating correlates positively with the International Knee Documentation Committee (IKDC) and the modified Cincinnati Knee Rating System (CKRS) total scores after knee surgery. STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 2. METHODS: Patients undergoing either anterior cruciate ligament (ACL) reconstruction or knee arthroscopy were prospectively given subjective evaluations yearly after surgery between January 2000 and June 2011. Subjective evaluations were obtained using modified CKRS and IKDC subjective knee surveys and a SANE rating. Interclass correlation coefficient was used to determine the correlation of the SANE rating to the survey total scores. Bland-Altman method was used to access precision and limits of agreement between scores. In addition, the data were analyzed according to sex and age categories (<18, 18-24, 25-40, >40 years). RESULTS: A total of 11,939 surveys were collected from 3209 patients (mean, 3.7 surveys/person; range, 1-22) after ACL reconstruction with a mean survey age of 35.2 ± 11.9 years (range, 13-72). A total of 4615 surveys were collected from 1813 patients (mean, 2.6 surveys/person; range, 1-17) after knee arthroscopy with a mean survey age of 47.4 ± 14.6 years (range, 11-88). For patients who underwent ACL reconstruction, the SANE rating had a moderate positive correlation of 0.66 to the total survey scores. For patients who underwent knee arthroscopies, the SANE rating had a strong positive correlation of 0.74 to total scores. There was minimal difference in correlations based on age group or sex. Bland-Altman analysis showed that the limits of agreement between the SANE score and the 2 surveys were met for at least 94% of patients in both patient groups. CONCLUSION: The SANE ratings exhibited moderate to strong positive correlations with the modified CKRS and IKDC subjective surveys after ACL reconstruction and knee arthroscopy for patients of all ages and both sexes.

Initial experience in the treatment of inherited mitochondrial disease with EPI-743.

Inherited mitochondrial respiratory chain disorders are progressive, life-threatening conditions for which there are limited supportive treatment options and no approved drugs. Because of this unmet medical need, as well as the implication of mitochondrial dysfunction as a contributor to more common age-related and neurodegenerative disorders, mitochondrial diseases represent an important therapeutic target. Thirteen children and one adult with genetically-confirmed mitochondrial disease (polymerase γ deficiency, n=4; Leigh syndrome, n=4; MELAS, n=3; mtDNA deletion syndrome, n=2; Friedreich ataxia, n=1) at risk for progressing to end-of-life care within 90 days were treated with EPI-743, a novel para-benzoquinone therapeutic, in a subject controlled, open-label study. Serial measures of safety and efficacy were obtained that included biochemical, neurological, quality-of-life, and brain redox assessments using technetium-99m-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) radionuclide imaging. Twelve patients treated with EPI-743 have survived; one polymerase γ deficiency patient died after developing pneumonia and one patient with Surf-1 deficiency died after completion of the protocol. Of the 12 survivors, 11 demonstrated clinical improvement, with 3 showing partial relapse, and 10 of the survivors also had an improvement in quality-of-life scores at the end of the 13-week emergency treatment protocol. HMPAO SPECT scans correlated with clinical response; increased regional and whole brain HMPAO uptake was noted in the clinical responders and the one subject who did not respond clinically had decreased regional and whole brain HMPAO uptake. EPI-743 has modified disease progression in >90% of patients in this open-label study as assessed by clinical, quality-of-life, and non-invasive brain imaging parameters. Data obtained herein suggest that EPI-743 may represent a new drug for the treatment of inherited mitochondrial respiratory chain disorders. Prospective controlled trials will be undertaken to substantiate these initial promising observations. Furthermore, HMPAO SPECT imaging may be a valuable tool for the detection of central nervous system redox defects and for monitoring response to treatments directed at modulating abnormal redox.

Towards a modern definition of vitamin E-evidence for a quinone hypothesis.

We report on the synthesis, biological and pharmacological activity of the tocoquinone natural product, α-tocopherol quinone (ATQ); an oxidative metabolite of α-tocopherol. ATQ is a potent cellular protectant against oxidative stress, whose biological activity is dependent upon its ability to undergo reversible two-electron redox cycling. ATQ is orally bioavailable, with a favorable pharmacokinetic profile and has demonstrated a beneficial clinical response in patients with Friedreich's ataxia. ATQ is a member of a broader class of vitamin E derived quinone metabolites which may be ascribable in whole or in part to the activity of vitamin E.

α-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging.

We report that α-tocotrienol quinone (ATQ3) is a metabolite of α-tocotrienol, and that ATQ3 is a potent cellular protectant against oxidative stress and aging. ATQ3 is orally bioavailable, crosses the blood-brain barrier, and has demonstrated clinical response in inherited mitochondrial disease in open label studies. ATQ3 activity is dependent upon reversible 2e-redox-cycling. ATQ3 may represent a broader class of unappreciated dietary-derived phytomolecular redox motifs that digitally encode biochemical data using redox state as a means to sense and transfer information essential for cellular function.

Impact of income management on store sales in the Northern Territory.

OBJECTIVE: To examine the impact of a government income management program on store sales. DESIGN AND SETTING: An interrupted time series analysis of sales data in 10 stores in 10 remote Northern Territory communities during 1 October 2006 to 30 September 2009, which included an 18-month period before income management; a 4-6-month period after the introduction of income management; a 3-month period that coincided with a government stimulus payment; and the remaining income-management period. MAIN OUTCOME MEASURES: Trends in (i) total store sales; (ii) total food and beverage sales; (iii) fruit and vegetables sales; (iv) soft drink sales; and v) tobacco sales. RESULTS: Modest monthly increases indicative of inflation were found for all outcome measures before the introduction of income management, except for soft drink sales, which remained constant. No change from the increasing rate of monthly sales before income management was seen in the first 4-6 months of income management or for the income-management period thereafter for total store sales, food and beverage sales, fruit and vegetable sales and tobacco sales. The rate of soft drink sales declined significantly with the introduction of income management and then increased significantly thereafter. The 3-month government stimulus payment period (during the period of income management) was associated with a significant increase in the rate of sales for all outcome measures. CONCLUSION: Income management independent of the government stimulus payment appears to have had no beneficial effect on tobacco and cigarette sales, soft drink or fruit and vegetable sales.

Microarray analysis of endophyte-infected and endophyte-free tall fescue.

Many grasses have mutualistic symbioses with fungi of the family Clavicipitaceae. Tall fescue can harbor the obligate endophyte, Neotyphodium coenophialum that is asexually propagated and transmitted via host seeds. Total RNA was isolated from pseudostems of known endophyte-infected (E+) and endophyte-free (E-) plants and tested in triplicate on the Affymetrix Wheat Genome Array GeneChip and Barley1 Genome Array GeneChip. Overall 14-15% and 17-18% of the probe sets were called present on the wheat and barley chips, respectively. In order to identify genes that were specifically differentially expressed between the E+ and E- tall fescue, a combination of both barley and wheat target sequences that were differentially expressed (greater than twofold) that were similar on both chips on both barley and wheat arrays yielded 32 probe set (genes) that were differentially expressed. Tall fescue ESTs were identified for a number of the probe sets that were differentially expressed on the barley and wheat arrays. PCR primers were designed to fescue ESTs and tested to verify the expression profile observed in the microarray experiments. Some primers confirmed the expected results, although in other cases no differences were observed between the E+ and E- plants, or the results were contrary to what was expected. Our results suggest that while some differentially expressed genes were identified by this method, the cross-species hybridization appears to have significant limitations for the transcriptome analysis of tall fescue.

Impact of gender and parent of origin on the phenotypic expression of hereditary nonpolyposis colorectal cancer in a large Newfoundland kindred with a common MSH2 mutation.

PURPOSE: This study was designed to provide precise estimates of death and cancer risks, by gender and parent of origin, in hereditary nonpolyposis colorectal cancer independent of mutation, geographic variation, and ascertainment bias. METHODS: A group of 12 families with a founder MSH2 mutation (nucleotide 943+3, A --> T) causing hereditary nonpolyposis colorectal cancer was identified in Newfoundland. Genetic testing was offered to those at 50 percent risk of inheriting the mutation. Medical records were reviewed to identify cancer types, age at onset of cancer, and age at death. Ascertainment bias was limited by analyzing only sibships with good ascertainment of genetic status (> or =50 percent of sibships had known genetic status). RESULTS: Of 302 family members with hereditary nonpolyposis colorectal cancer or at 50 percent risk, 151 (50 percent) were considered to be mutation carriers, 96 (32 percent) were mutation negative, and 55 (18 percent) were of unknown mutation status. By age 50 years, 72 percent of males and 72 percent of females who were hereditary nonpolyposis colorectal cancer mutation carriers had developed cancer. The age-related risks of colorectal cancer or of death of cancer were significantly higher in males than in females (relative risk = 2.8, P = 0.0001 and relative risk = 2.1, P = 0.01, respectively). The mutation was transmitted by the mother more frequently than the father. Females who inherited the mutation from their father had an increased risk of developing colorectal cancer (relative risk = 2.5, P = 0.05) and of dying of cancer (relative risk = 2.7, P = 0.04) compared with females who inherited the mutation from their mother. CONCLUSIONS: Investigation of large kindreds from the same geographic area who share the same MSH2 mutation and in whom family members have been identified with little ascertainment bias suggests that the risks for colorectal cancer and death of cancer are higher for male mutation carriers than for females and that females who inherit the mutation from their father are at higher risk of colorectal cancer than females who inherit the mutation from their mother.