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Summary: Background: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes. Methods: The PHOSP-COVID study is a multicentre, long-term follow-up study of adults discharged from hospital between 1 February 2020 and 31 March 2021 in the UK following COVID-19, involving detailed assessment at 5 and 12 months after discharge. The association between diabetes status and outcomes were explored using multivariable linear and logistic regressions. Findings: People with diabetes who survived hospital admission with COVID-19 display worse physical outcomes compared to those without diabetes at 5- and 12-month follow-up. People with diabetes displayed higher fatigue (only at 5 months), frailty, lower physical performance, and health-related quality of life and poorer cognitive function. Differences in outcomes between diabetes status groups were largely consistent from 5 to 12-months. In regression models, differences at 5 and 12 months were attenuated after adjustment for BMI and presence of other long-term conditions. Interpretation: People with diabetes reported worse physical outcomes up to 12 months after hospital discharge with COVID-19 compared to those without diabetes. These data support the need to reduce inequalities in long-term physical and mental health effects of SARS-CoV-2 infection in people with diabetes. Funding: UK Research and Innovation and National Institute for Health Research. The study was approved by the Leeds West Research Ethics Committee (20/YH/0225) and is registered on the ISRCTN Registry (ISRCTN10980107).

Summary: Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group—robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)—at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.

Jazan Industrial Economic City (JIEC) is located on the Red Sea coast in the province of Jazan, southwest of Saudi Arabia anchors diverse heavy and secondary industries in the energy, water desalination, petroleum, aluminum, copper, refineries, pharmaceuticals and food manufacturing fields. These various industries generate a large quantity of industrial wastewaters containing various toxicants. The present work represents ecologically beneficial alternatives for the advancement of environmental biotechnology, which could help mitigate the adverse impacts of environmental pollution resulting from petroleum refining effluents. The mycobiome (32 fungal strains) isolated from the industrial wastewater of the refinery sector in Jazan were belonged to five fungal genera including Fusarium, Verticillium, Purpureocillium, Clavispora and Scedosporium with a distribution percentage of 31.25, 21.88, 15.63, 12.50 and 18.75 %, respectively.These isolates showed multimetals tolerance and bioremoval efficiency against a large number of heavy metals (Fe2+, Ni2+, Cr6+, Zn2+, As3+, Cu2+, Cd2+, Pb2+, Ag+ and Hg2+) along with potent bioremediation activity toward crude oil and the polycyclic aromatic hydrocarbons. Interestingly, the mycobiome resistance patterns obtained against different classes of fungal antibiotics including azole (fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole and ketoconazole), echinocandin (anidulafungin, caspofungin and micafungin) and polyene (amphotericin B) drugs proved the prevalence of antibiotic resistance among the mycobiome of refinery industry in Saudi Arabia is relatively low. The fungal isolate under isolation code JAZ-20 showed the highest bioremoval efficiency against heavy metals (90.8–100.0 %), crude oil (89.50 %), naphthalene (96.7 %), phenanthrene (92.52 %), fluoranthene (100.0 %), anthracene (90.34 %), pyrene (85.60 %) and chrysene (83.4 %). It showed the highest bioremoval capacity ranging from 85.72 % to 100.0 % against numerous pollutants found in a wide array of industrial effluents, including diclofenac, ibuprofen, carbamazepine, acetaminophen, sulfamethoxazole, bisphenol, bleomycin, vincristine, dicofol, methyl parathion, atrazine, diuron, dieldrin, chlorpyrifos, profenofos and phenanthrene. The isolate JAZ-20 was chosen for molecular typing, cytotoxicity assessment, analysis of volatile compounds and optimization investigations. Based on phenotypic, biochemical and phylogenetic analysis, strain JAZ-20 identified as Scedosporium apiospermum JAZ-20. This strain is newly discovered in industrial effluents in Saudi Arabia. Fungal strain JAZ-20 consistently produced various types of saturated and unsaturated fatty acids. the main fatty acids were C14:0 (1.95 %), iso-C14:0 (2.98 %), anteiso-C14:0 (2.13 %), iso-C15:0 (9.16 %), anteiso-C15:0 (11.75 %), C15:0 (7.42 %), C15:1 (2.37 %), anteiso-C16:0 (3.4 %), C16:0 (10.3 %), iso-C16:0 (9.5 %), C17:1 (1.36 %), anteiso-C17:1 (8.64 %), iso-C18:0 (11.0 %), C18:0 (3.63 %), anteiso-C19:0 (3.78 %), anteiso-C20:0 (2.0 %), iso-C21:0 (2.44 %), C23:0 (1.15 %), and C24:0 (2.17 %). These fatty acids serve as natural and eco-friendly antifungal agents, promoting fungal resistance and inhibiting the production of mycotoxins in the environment. Despite being an environmental isolate, its cytotoxicity was assessed against both normal and cancerous human cell lines. The IC50 values of JAZ-20 extract were 8.92, 10.41, 20.0, 16.5, and 40.0 μg/mL against WI38, MRC5, MCF10A, HEK293 and HDFs normal cells and 43.26, 33.75, and 40.0 μg/mL against liver (HepG2), breast (A549) and cervix (HeLa) cancers, respectively. Based on gas chromatography-mass spectrometry (GC-MS), analysis the extract of S. apiospermum JAZ-20 showed 47 known volatile compounds (VOCs) for varied and significant biological activities. Enhancing the bioremoval efficiency of heavy metals from actual refining wastewater involves optimizing process parameters. The parameters optimized were the contact time, the fungal biomass dosage, pH, temperature and agitation rate.

Summary: Phasing of heterozygous alleles is critical for interpretation of cis-effects of disease-relevant variation. We sequenced 477 individuals with cystic fibrosis (CF) using linked-read sequencing, which display an average phase block N50 of 4.39 Mb. We use these samples to construct a graph representation of CFTR haplotypes, demonstrating its utility for understanding complex CF alleles. These are visualized in a Web app, CFTbaRcodes, that enables interactive exploration of CFTR haplotypes present in this cohort. We perform fine-mapping and phasing of the chr7q35 trypsinogen locus associated with CF meconium ileus, an intestinal obstruction at birth associated with more severe CF outcomes and pancreatic disease. A 20-kb deletion polymorphism and a PRSS2 missense variant p.Thr8Ile (rs62473563) are shown to independently contribute to meconium ileus risk (p = 0.0028, p = 0.011, respectively) and are PRSS2 pancreas eQTLs (p = 9.5 × 10−7 and p = 1.4 × 10−4, respectively), suggesting the mechanism by which these polymorphisms contribute to CF. The phase information from linked reads provides a putative causal explanation for variation at a CF-relevant locus, which also has implications for the genetic basis of non-CF pancreatitis, to which this locus has been reported to contribute.

Introduction: Antibiotic-resistant Gram-negative bacteria are of a growing concern globally, especially those producing enzymes conferring resistance. OXA-48-like carbapenemases hydrolyze most β-lactam antibiotics, with typically low-level hydrolysis of carbapenems, but have limited effect on broad-spectrum cephalosporins. These are frequently co-expressed with extended spectrum β-lactamases, especially CTX-M-15, which typically shows high level resistance to broad-spectrum cephalosporins, yet is carbapenem susceptible. The combined resistance profile makes the need for successful detection of these specific resistance determinants imperative for effective antibiotic therapy. Objectives: The objective of this study is to detect and identify OXA-48-like and CTX-M-15 enzymes using mass spectrometry, and to subsequently develop a method for detection of both enzyme types in combination with liquid chromatography. Methods: Cells grown in either broth or on agar were harvested, lysed, and, in some cases buffer-exchanged. Lysates produced from bacterial cells were separated and analyzed via liquid chromatography with mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS/MS). Results: The intact proteins of OXA-48, OXA-181, and OXA-232 (collectively OXA-48-like herein) and CTX-M-15 were characterized and detected. Acceptance criteria based on sequence-informative fragments from each protein group were established as confirmatory markers for the presence of the protein(s). A total of 25 isolates were successfully tested for OXA-48 like (2), CTX-M-15 (3), or expression of both (7) enzymes. Thirteen isolates served as negative controls. Conclusions: Here we present a method for the direct and independent detection of both OXA-48-like carbapenemases and CTX-M-15 β-lactamases using LC-MS/MS. The added sensitivity of MS/MS allows for simultaneous detection of at least two co-eluting, co-isolated and co-fragmented proteins from a single mass spectrum.

A survey of wild macrofungi associated with temperate evergreen forests of the Bharsar region of the Pauri Garhwal district, Uttarakhand, India, yielded specimens of 12 different species representing 10 genera. During the field work, we also collected several fruiting bodies unique to their respective genera. These included (1) a fruiting body with a small cap and long slender stipe belonging to the group of species within the genus Lactarius (subgenus Russularia) characterized by a rusty red cap and white latex; (2) a tall species of Hebeloma with a veil and thin crowded gills, and (3) a species of Hygrocybe that stains black. Owing to their special characteristic features, the specimens of Lactarius and Hebeloma are likely to be species new to science, but this requires further investigation. In addition, nine other taxa are briefly described herein, with their major macroscopic features noted. This is the first report of the macrofungal wealth from this diverse forest of the Bharsar region in the Uttarakhand Himalaya, India. Keywords: Basidiomycota, Diversity, Higher fungi, Northern India, Uttarakhand

Self-binding directives (SBDs) are an ethically controversial type of advance decision making involving advance requests for involuntary treatment. This study systematically reviewed the academic literature on psychiatric SBDs to elucidate reasons for and against their use in psychiatric practice. Full-text articles were thematically analysed within the international, interdisciplinary authorship team to produce a hierarchy of reasons. We found 50 eligible articles. Reasons for SBD use were promoting service user autonomy, promoting wellbeing and reducing harm, improving relationships, justifying coercion, stakeholder support, and reducing coercion. Reasons against SBD use were diminishing service user autonomy, unmanageable implementation problems, difficulties with assessing mental capacity, challenging personal identity, legislative issues, and causing harm. A secondary finding was a clarified concept of capacity-sensitive SBDs. Future pilot implementation projects that operationalise the clarified definition of capacity-sensitive SBDs with safeguards around informed consent, capacity assessment, support for drafting, and independent review are required., Competing Interests: Declaration of interests GO is special advisor to the Royal College of Psychiatrists UK on mental health and capacity law (England and Wales). All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Self-binding directives instruct clinicians to overrule treatment refusal during future severe episodes of illness. These directives are promoted as having the potential to increase autonomy for individuals with severe episodic mental illness. Although lived experience is central to their creation, the views of service users on self-binding directives have not been investigated substantially. This study aimed to explore whether reasons for endorsement, ambivalence, or rejection given by service users with bipolar disorder can address concerns regarding self-binding directives, decision-making capacity, and human rights., Methods: This qualitative study used data from an internet-based survey distributed to the mailing list of the UK charity Bipolar UK, which contained multiple closed and open questions on advance decision making for patients with bipolar disorder. We included participants who reported that they have been diagnosed with bipolar disorder by a professional (doctor or psychiatrist). In a previous study, quantitative analysis of a closed question about self-binding directives had shown endorsement among a high proportion of participants with bipolar disorder who completed the survey. In this study, we did a thematic analysis of responses from those participants who answered a subsequent open question about reasons for their view. Research was done within a multidisciplinary team, including team members with clinical, legal, and ethical expertise, and lived experience of bipolar disorder. Ideas and methods associated with all these areas of expertise were used in the thematic analysis to gain insight into the thoughts of individuals with bipolar disorder about self-binding directives and associated issues., Findings: Between Oct 23, 2017, and Dec 5, 2017, 932 individuals with a self-reported clinical diagnosis of bipolar disorder completed the internet survey, with 565 individuals (154 men, 400 women, 11 transgender or other), predominantly white British, providing free-text answers to the open question. 463 (82%) of the 565 participants endorsed self-binding directives, of whom 411 (89%) describing a determinate shift to distorted thinking and decision making when unwell as their key justification. Responses indicating ambivalence (37 [7%) of the 565 responses) were dominated by logistical concerns about the drafting and implementation of self-binding directives, whereas those who rejected self-binding directives (65 [12%] of the 565 responses) cited logistical concerns, validity of their thinking when unwell, and potential contravention of human rights., Interpretation: This study is, to our knowledge, the first large study assessing the reasons why mental health service users might endorse or reject the use of self-binding directives. The findings provide empirical support for introducing self-binding directives into mental health services as well as advance decision-making practice and policy, and might help address enduring ethical concerns surrounding possible implementation of the directive while a person retains decision-making capacity. The opinions expressed here in responses given by multiple service users with bipolar disorder challenge a prominent view within international disability rights debates that involuntary treatment and recognition of impaired mental capacity constitute inherent human rights violations., Funding: The Wellcome Trust., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 License. Published by Elsevier Ltd.. All rights reserved.)

While planned complex suicides utilize more than one method, on occasion a planned suicide merely involves augmentation of the lethality of the chosen single method. A study was undertaken of augmented suicidal drownings from Forensic Science SA, Adelaide, Australia over a 25-year period (1993-2017). 493 cases (M:F 2.6:1) were found in which death was attributed to drowning. The age range for males was 7mths-93yrs (mean 43.7yrs) and for females 11mths-87yrs (mean 48.2yrs). A subset of 116 suicidal drownings (M:F 1.2:1) had a male age range of 17-86yrs (mean 52.3yrs) and for females 19-68yrs (mean 57.4yrs). 16 individuals in this group (3% of drownings overall) had utilised weights to assist in their submersion (M:F 1.7:1), with an age range for males of 30-84yrs (mean 63.3yrs) and for females 38-81yrs (mean 54.6yrs). The most common weights were bricks, rocks or concrete blocks (N = 7) with weights that were tied to the body most often attached to the neck (N = 7). Augmented drowning by using weights to enhance submersion was not common in this population and was predominantly a technique utilised by older males. Augmentation of a suicide method may be extremely useful support at a death scene to exclude an accident., Competing Interests: Declaration of competing interest None., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Although the diagnosis of drowning may appear straightforward the reality is that it is sometimes one of the most difficult in forensic pathology. To begin with, there is no universal agreement on what constitutes drowning with some definitions using the term in the absence of a lethal outcome. Next are the significant problems that arise in finding immersed bodies and in assessing the death scene. Prolonged post mortem intervals are associated with artefactual modifications of the body from putrefaction and post mortem animal predation. Both of these may create and disguise injuries. The absence of pathognomonic pathological features at autopsy and the presence of potentially life threatening underlying organic illnesses complicate determination of both the cause and manner of death. There may even be no autopsy findings to indicate that immersion had occurred. Finally, the unreliability of laboratory tests with significant overlap with control cases where death had no association with immersion presents further problems. Thus lethal drowning remains a complex event that requires the use of a wide variety of information sources, not just data gleaned from the dissection table., (Copyright © 2019 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB) that is most often transmitted by the inhalation of bacteria-containing aerosols. While there has been a decline in numbers of cases in certain countries, large population movements, the increasing emergence of drug-resistant strains and the association with human immunodeficiency virus (HIV) infection make it a disease that is increasingly seen in forensic practice. Mortuary staff are at risk of infection from penetrating sharp injuries, droplet inhalation, ingestion, direct inoculation, through skin breaks or through mucous membranes of the eyes, nose and mouth. While the health and safety measures outlined by agencies may vary slightly, the principles of handling infectious autopsy cases remain the same with awareness and education, immunisation and regular tuberculin testing of staff, pre-necropsy screening of decedents, use of personal protective equipment, and the implementation of safe sharps practices and measures to reduce aerosol formation., (Copyright © 2019. Published by Elsevier Ltd.)

Tattoos have been previously linked to high-risk behaviours involving drug use, sexual promiscuity, mental health disorders such as depression and subsequent suicidality, aberrant personality traits including lack of sociability and reduced inhibition, psychopathy and schizophrenia. All of these have been associated with violent and early deaths. Given the recent increase in numbers of individuals being tattooed in Western communities, a retrospective study was undertaken of 100 consecutive autopsy cases with tattoos over a 5-year period from 2013 to 2017, with age and sex-matched controls. Although those with ≥5 tattoo regions were slightly younger than those with <5, 47.4 compared to 49.7 years, this did not reach statistical significance (p = 0.35). Similarly, there were no significant differences in the cause and manner of death among the groups (p = 0.09). This study has, therefore, shown no significant association between the number of tattoos and premature mortality, or between the cause and manner of death and the presence or absence of tattoos. Previous stereotypes regarding tattooed individuals may no longer apply., (Copyright © 2019 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Objective: To evaluate content and face validity of a collaboration readiness assessment tool developed to facilitate collaborative efforts to implement policy, systems, and environment changes in Supplemental Nutrition Assistance Program-Education (SNAP-Ed)., Methods: Evaluation of the validity of the tool involved 2 steps. Step 1 was conducted with 4 subject matter experts to evaluate content validity. Step 2 used an iterative cognitive testing process with 4 rounds and 16 SNAP-Ed staff and community partners to evaluate face validity., Results: Subject matter experts found that survey items appropriately matched the content area indicated and adequately covered collective efficacy, change efficacy, and readiness. Cognitive testing with SNAP-Ed staff and partners informed modifications and resulted in adequate face validity., Conclusions and Implications: The ability to measure collaboration readiness will allow agencies and community partners that implement SNAP-Ed to target areas that facilitate collaboration efforts needed for policy, systems, and environment change and collective efficacy. Further cognitive testing of the tool with other populations is needed to ensure its applicability and usefulness. Evaluation of the reliability of the tool with a broad range of SNAP-Ed programs and community agencies is also recommended., (Copyright © 2017 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.)

Genetic understanding of motor neuron disease (MND) has evolved greatly in the past 10 years, including the recent identification of association between MND and variants in TBK1 and NEK1. Our aim was to determine the frequency of pathogenic variants in known MND genes and to assess whether variants in TBK1 and NEK1 contribute to the burden of MND in the Scottish population. SOD1, TARDBP, OPTN, TBK1, and NEK1 were sequenced in 441 cases and 400 controls. In addition to 44 cases known to carry a C9orf72 hexanucleotide repeat expansion, we identified 31 cases and 2 controls that carried a loss-of-function or pathogenic variant. Loss-of-function variants were found in TBK1 in 3 cases and no controls and, separately, in NEK1 in 3 cases and no controls. This study provides an accurate description of the genetic epidemiology of MND in Scotland and provides support for the contribution of both TBK1 and NEK1 to MND susceptibility in the Scottish population., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Picosecond-pulsed ultraviolet-laser (UV-355 nm) assisted atom probe tomography (APT) was used to analyze protective, thermally grown chromium oxides formed on stainless steel. The influence of analysis parameters on the thermal tail observed in the mass spectra and the chemical composition is investigated. A new parameter termed "laser sensitivity factor" is introduced in order to quantify the effect of laser energy on the extent of the thermal tail. This parameter is used to compare the effect of increasing laser energy on thermal tails in chromia and chromite samples. Also explored is the effect of increasing laser energy on the measured oxygen content and the effect of specimen base temperature and laser pulse frequency on the mass spectrum. Finally, we report a preliminary analysis of molecular ion dissociations in chromia., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Introduction: The purpose of this study was to investigate the antifungal activity of Endosequence Root Repair Material (ERRM; Brasseler USA, Savannah, GA) as compared with mineral trioxide aggregate (MTA) using Candida albicans., Methods: All materials were packed into sterilized intravenous tubing to obtain standardized samples and allowed to set for 3 or 24 hours and then exposed to a suspension of C. albicans for incubations of 24 or 48 hours. To analyze the mechanisms of the material's antifungal activity, additional samples of each test material were prepared in the same manner and allowed to set for 24 hours; these were then incubated in a culture medium for 24 hours. The pH of each conditioned media was measured before transferring to wells containing C. albicans. The development of biofilm was analyzed after 24 and 48 hours with 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-([phenyl amino] carbonyl)-2H-tetrazolium hydroxide reduction assay., Results: Materials in both experimental groups significantly limited biofilm formation at each interval (ie, 24 and 48 hours). After incubating for a 24-hour period in the presence of C. albicans, ERRM in both experimental groups showed a reduction in biofilm formation that was statistically significant in comparison with MTA. However, when set for 24 hours and incubated for 48 hours, gray MTA and white MTA showed a more substantial reduction in biofilm formation than comparable samples of ERRM. Cultured media conditioned with test materials showed statistically significant antifungal biofilm activity after 48 hours., Conclusions: All materials tested have comparable antifungal biofilm activity. It appeared that changing the environment, such as the pH, contributed to this activity., (Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Enterocyte apoptosis in necrotizing enterocolitis is partly due to the elaboration of toxic intermediates of nitric oxide (NO), such as peroxynitrite (PN). Because p38 mitogen-activated protein kinase (MAPK) and serine-threonine kinase (AKT) are well-characterized pro- and anti-apoptotic mediators, respectively, we hypothesized that PN could induce enterocyte apoptosis via activation of p38 and deactivation of AKT. To test this hypothesis, the rat intestinal cell line, IEC-6, was treated with PN. PN caused phosphorylation of p38, its upstream activator, MKK3/6, and downstream effector, transcription factor ATF-2. PN-induced apoptosis was inhibited by the p38 inhibitor, SB202190, and by p38 siRNA. PN decreased AKT phosphorylation; this effect was abrogated by pre-treatment with SB202190 or p38 siRNA. PN exposure also increased the activity of the protein phosphatase 2A (PP2A). These data demonstrate that PN-mediated apoptosis depends on the p38 pathway and that p38 mediates deactivation of AKT survival pathways possibly by the involvement of PP2A.

Background: Childhood obesity is a major public health problem in the United States, particularly among American Indian communities., Objective: The objective was to evaluate the effectiveness of a school-based, multicomponent intervention for reducing percentage body fat in American Indian schoolchildren., Design: This study was a randomized, controlled, school-based trial involving 1704 children in 41 schools and was conducted over 3 consecutive years, from 3rd to 5th grades, in schools serving American Indian communities in Arizona, New Mexico, and South Dakota. The intervention had 4 components: 1) change in dietary intake, 2) increase in physical activity, 3) a classroom curriculum focused on healthy eating and lifestyle, and 4) a family-involvement program. The main outcome was percentage body fat; other outcomes included dietary intake, physical activity, and knowledge, attitudes, and behaviors., Results: The intervention resulted in no significant reduction in percentage body fat. However, a significant reduction in the percentage of energy from fat was observed in the intervention schools. Total energy intake (by 24-h dietary recall) was significantly reduced in the intervention schools but energy intake (by direct observation) was not. Motion sensor data showed similar activity levels in both the intervention and control schools. Several components of knowledge, attitudes, and behaviors were also positively and significantly changed by the intervention., Conclusions: These results document the feasibility of implementing a multicomponent program for obesity prevention in elementary schools serving American Indian communities. The program produced significant positive changes in fat intake and in food- and health-related knowledge and behaviors. More intense or longer interventions may be needed to significantly reduce adiposity in this population.