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1.
Obes Rev ; : e13808, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39032149

ABSTRACT

This systematic review with the Delphi study aimed to identify effective and resource-efficient (optimal) strategies for recruiting schools into health promotion interventions in the United States. A literature search was conducted in PubMed, Cochrane Library, and CINAHL (EBSCO). A total of 116 interventions reported in 160 articles were included. Most school-based interventions did not report data regarding school recruitment duration (81%), target school size (63%), and school recruitment strategies (78%). Further, no details were provided regarding the reasons for declining to participate despite being eligible. For the Delphi, responses from 23 researchers in school-based clinical trials were collected. A qualitative descriptive approach was used for coding responses and collapsed into higher-order categories based on school recruitment strategies. Delphi participants reported that (1) creating new or leveraging pre-existing partnerships, (2) intervention champion, (3) minimal school disruptions, (4) working with open mind/flexibility, and (5) transparent communication are the most optimal school recruitment strategies. Staff time and travel were the most frequently reported costs for implementing those strategies. The overall trend in school-based obesity prevention intervention studies illustrates the importance of a better understanding school recruitment. Improved reporting can allow researchers to budget their time and resources better and provide greater confidence in reaching their target school size.

2.
J Clin Invest ; 134(12)2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38950322

ABSTRACT

Cytoplasmic and nuclear iron-sulfur (Fe-S) enzymes that are essential for genome maintenance and replication depend on the cytoplasmic Fe-S assembly (CIA) machinery for cluster acquisition. The core of the CIA machinery consists of a complex of CIAO1, MMS19 and FAM96B. The physiological consequences of loss of function in the components of the CIA pathway have thus far remained uncharacterized. Our study revealed that patients with biallelic loss of function in CIAO1 developed proximal and axial muscle weakness, fluctuating creatine kinase elevation, and respiratory insufficiency. In addition, they presented with CNS symptoms including learning difficulties and neurobehavioral comorbidities, along with iron deposition in deep brain nuclei, mild normocytic to macrocytic anemia, and gastrointestinal symptoms. Mutational analysis revealed reduced stability of the variants compared with WT CIAO1. Functional assays demonstrated failure of the variants identified in patients to recruit Fe-S recipient proteins, resulting in compromised activities of DNA helicases, polymerases, and repair enzymes that rely on the CIA complex to acquire their Fe-S cofactors. Lentivirus-mediated restoration of CIAO1 expression reversed all patient-derived cellular abnormalities. Our study identifies CIAO1 as a human disease gene and provides insights into the broader implications of the cytosolic Fe-S assembly pathway in human health and disease.


Subject(s)
Iron-Sulfur Proteins , Humans , Iron-Sulfur Proteins/genetics , Iron-Sulfur Proteins/metabolism , Male , Female , Neuromuscular Diseases/genetics , Neuromuscular Diseases/enzymology , Neuromuscular Diseases/metabolism , Neuromuscular Diseases/pathology , Child , Cell Nucleus/metabolism , Cell Nucleus/enzymology , Cell Nucleus/genetics , Cytoplasm/metabolism , Cytoplasm/enzymology , Metallochaperones
3.
Acad Pediatr ; 24(5S): 19-24, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38991797

ABSTRACT

The ability to exercise autonomy in achieving reproductive health goals necessitates access to contraceptive and reproductive health information and medical care. Finding trusted, comprehensive, consistent and affordable reproductive care is particularly challenging for immigrants living in the United States, especially for those without legal immigration status and for those who prefer a language other than English. In immigrant communities, sexual and reproductive health (SRH) knowledge, contraceptive choice, and family planning are influenced by many factors including tension between traditional and adopted cultural norms, limited English proficiency, restricted health care access, and structural racism. The family-centered model and longitudinal nature of relationships in pediatric primary care pose a unique opportunity to support immigrant families across the lifespan in obtaining SRH information and achieving reproductive health goals. Here, we present the unique vulnerabilities faced by immigrants seeking SRH services in the United States including both the upstream and downstream health effects of immigration status on family health. We then describe four time points across the lifespan where pediatricians can support SRH, including examples of existing SRH programming designed or adapted for immigrant families. Finally, we discuss opportunities to advance research, policy, education, and clinical care related to SRH equity for immigrant families.


Subject(s)
Emigrants and Immigrants , Reproductive Health , Sexual Health , Humans , United States , Female , Health Services Accessibility , Male , Reproductive Health Services , Pediatricians , Adolescent , Child , Adult
4.
bioRxiv ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-39005470

ABSTRACT

Cartilaginous fishes (chimaeras and elasmobranchs -sharks, skates and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic and morphological data in the small-spotted catshark Scyliorhinus canicula to shed light on the evolution of sensory organs. We first characterise general aspects of the catshark genome, confirming the high conservation of genome organisation across cartilaginous fishes, and investigate population genomic signatures. Taking advantage of a dense sampling of transcriptomic data, we also identify gene signatures for all major organs, including chondrichthyan specializations, and evaluate expression diversifications between paralogs within major gene families involved in sensory functions. Finally, we combine these data with 3D synchrotron imaging and in situ gene expression analyses to explore chondrichthyan-specific traits and more general evolutionary trends of sensory systems. This approach brings to light, among others, novel markers of the ampullae of Lorenzini electro-sensory cells, a duplication hotspot for crystallin genes conserved in jawed vertebrates, and a new metazoan clade of the Transient-receptor potential (TRP) family. These resources and results, obtained in an experimentally tractable chondrichthyan model, open new avenues to integrate multiomics analyses for the study of elasmobranchs and jawed vertebrates.

5.
J Pain Res ; 17: 2079-2097, 2024.
Article in English | MEDLINE | ID: mdl-38894862

ABSTRACT

Purpose: An early-stage, multi-centre, prospective, randomised control trial with five-year follow-up was approved by Health Research Authority to compare the efficacy of a minimally invasive, laterally implanted interspinous fixation device (IFD) to open direct surgical decompression in treating lumbar spinal stenosis (LSS). Two-year results are presented. Patients and Methods: Forty-eight participants were randomly assigned to IFD or decompression. Primary study endpoints included changes from baseline at 8-weeks, 6, 12 and 24-months follow-ups for leg pain (visual analogue scale, VAS), back pain (VAS), disability (Oswestry Disability Index, ODI), LSS physical function (Zurich Claudication Questionnaire), distance walked in five minutes and number of repetitions of sitting-to-standing in one minute. Secondary study endpoints included patient and clinician global impression of change, adverse events, reoperations, operating parameters, and fusion rate. Results: Both treatment groups demonstrated statistically significant improvements in mean leg pain, back pain, ODI disability, LSS physical function, walking distance and sitting-to-standing repetitions compared to baseline over 24 months. Mean reduction of ODI from baseline levels was between 35% and 56% for IFD (p<0.002), and 49% to 55% for decompression (p<0.001) for all follow-up time points. Mean reduction of IFD group leg pain was between 57% and 78% for all time points (p<0.001), with 72% to 94% of participants having at least 30% reduction of leg pain from 8-weeks through 24-months. Walking distance for the IFD group increased from 66% to 94% and sitting-to-standing repetitions increased from 44% to 64% for all follow-up time points. Blood loss was 88% less in the IFD group (p=0.024) and operating time parameters strongly favoured IFD compared to decompression (p<0.001). An 89% fusion rate was assessed in a subset of IFD participants. There were no intraoperative device issues or re-operations in the IFD group, and only one healed and non-symptomatic spinous process fracture observed within 24 months. Conclusion: Despite a low number of participants in the IFD group, the study demonstrated successful two-year safety and clinical outcomes for the IFD with significant operation-related advantages compared to surgical decompression.

6.
J Acad Nutr Diet ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38825045

ABSTRACT

BACKGROUND: Diet quality has been found to be related to cognitive health in school-aged children. However, this relationship remains understudied among Hispanic preschool-aged children, who are vulnerable to poor dietary habits and low cognitive development due to socioeconomic, cultural, and structural disparities. OBJECTIVE: This longitudinal study evaluated whether the diet quality of preschool-aged children would be associated with executive functions (EFs) in later childhood. DESIGN: This is a secondary analysis of a longitudinal study of Hispanic preschool-aged children (age 4 and 5 years) at baseline (Time 1) and 18 months (Time 2). PARTICIPANTS AND SETTING: This study included 185 mother-child dyads with complete data at Time 1, recruited through Head Start centers in Houston, TX, beginning in 2011. MAIN OUTCOME MEASURES: Mothers reported on their child's dietary intake via 3 24-hour recalls, which was used to calculate Healthy Eating Index (HEI)-2010 component and total scores. Laboratory tasks assessed cold EFs (tapping and Flexible Item Selection Tasks) and hot EFs (delay of gratification and gift-wrapping tasks). Whereas higher scores on tapping, Flexible Item Selection Task, and delay of gratification tasks represent a high EF, higher scores in gift-wrapping task represent a low EF. STATISTICAL ANALYSES PERFORMED: Hierarchical linear regression analyses assessed the relationship between diet quality, as measured by HEI-2010 total and component scores, at Time 1 (independent variables) and EF outcomes (dependent variables) at Time 2, controlling for child sex, age, body mass index z score, and EF at Time 1. RESULTS: HEI-2010 component score for fatty acids (b = -.13; P = .04) and seafood and plant proteins (b = .09; P = .05), were respectively related to later cold and hot EFs of Hispanic preschool-aged children. Other HEI components or the overall score did not predict EFs. CONCLUSIONS: This study shows that specific HEI components support cold and hot EFs development among Hispanic preschool-aged children, but total HEI-2010 score does not. Experimental research is needed to assess the influence of dietary interventions on cognitive development of Hispanic preschool-aged children.

7.
NPJ Vaccines ; 9(1): 106, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877036

ABSTRACT

The safety, reactogenicity, and immunogenicity of 3 doses of ExPEC10V (VAC52416), a vaccine candidate to prevent invasive Escherichia coli disease, were assessed in a phase 1/2a study (NCT03819049). In Cohort 1, ExPEC10V was well tolerated; the high dose was selected as optimal and further characterized in Cohort 2. Cohort 2 comprised a maximum 28-day screening, vaccination (Day 1), double-blind 181-day follow-up, and open-label long-term follow-up until Year 1. Healthy participants (≥60 years) with a history of urinary tract infection (UTI) within 5 years were randomized to receive ExPEC10V or placebo. The primary endpoint evaluated the safety and reactogenicity of ExPEC10V (solicited local and systemic AEs [until Day 15]; unsolicited AEs [until Day 30], SAEs [until Day 181], and immunogenicity [Day 30]) via multiplex electrochemiluminescent (ECL) and multiplex opsonophagocytic assay (MOPA). 416 participants (ExPEC10V, n = 278; placebo, n = 138) were included (mean age [SD], 68.8 [6.52] years; female, 79.6%; White, 96.1%). The incidence of solicited AEs was higher with ExPEC10V (local, 50.0% [n = 139]; systemic, 50.0% [n = 139]) than placebo (15.9% [n = 22]; 38.4% [n = 53]); rates of unsolicited AEs were comparable (ExPEC10V, 28.4% [n = 79]; placebo, 26.1% [n = 36]). No vaccine-related SAEs or deaths were reported. ExPEC10V elicited a robust antibody-mediated immunogenic response across all serotypes with ECL (Day 30 geometric mean fold increase, 2.33-8.18) and demonstrated functional opsonophagocytic killing activity across all measured serotypes (Day 30 geometric mean fold increase, 1.81-9.68). ExPEC10V exhibited an acceptable safety profile and a robust vaccine-induced functional immunogenic response in participants with a history of UTI. Clinical trial registration details: https://clinicaltrials.gov/study/NCT03819049 .

8.
Qual Life Res ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38842645

ABSTRACT

PURPOSE: To examine [a] the association of caregiver health-related quality of life (HRQOL) and service member/veteran (SMV) neurobehavioral outcomes with caregiver resilience; [b] longitudinal change in resilience at the group and individual level; and [c] the magnitude of change at the individual level. METHODS: Caregivers (N = 232) of SMVs with traumatic brain injury completed a resilience measure, and 18 caregiver HRQOL and SMV neurobehavioral outcome measures at a baseline evaluation and follow-up evaluation three years later. Caregivers were divided into two resilience groups at baseline and follow-up: [1] Low Resilience (≤ 45 T, baseline n = 99, follow-up n = 93) and [2] High Resilience (> 45 T, baseline n = 133, follow-up n = 139). RESULTS: At baseline and follow-up, significant effects were found between Low and High Resilience groups for the majority of outcome measures. There were no significant differences in resilience from baseline to follow-up at the group-mean level. At the individual level, caregivers were classified into four longitudinal resilience groups: [1] Persistently Low Resilience (Baseline + Follow-up = Low Resilience, n = 60), [2] Reduced Resilience (Baseline = High Resilience + Follow-up = Low Resilience, n = 33), [3] Improved Resilience (Baseline = Low Resilience + Follow-up = High Resilience, n = 39), and [4] Persistently High Resilience (Baseline + Follow-up = High Resilience, n = 100). From baseline to follow-up, approximately a third of the Reduced and Improved Resilience groups reported a meaningful change in resilience (≥ 10 T). Nearly all of the Persistently High and Persistently Low Resilience groups did not report meaningful change in resilience (< 10 T). CONCLUSION: Resilience was not a fixed state for all caregivers. Early intervention may stall the negative caregiving stress-health trajectory and improve caregiver resilience.

10.
Psychol Trauma ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38913717

ABSTRACT

OBJECTIVE: To examine elevated symptoms on health-related quality of life (HRQOL) measures over 2 years in caregivers of service members with traumatic brain injury (TBI). To compare outcomes to caregivers of veterans. METHOD: Caregivers (N = 315) were classified into two groups: (a) service member caregiver group (n = 55) and (b) veteran caregiver group (n = 260). Caregivers completed 17 HRQOL measures at a baseline evaluation and follow-up evaluation 24 months later. RESULTS: In the service member caregiver group, the highest frequency of clinically elevated T-scores (≥ 60 T) at baseline and follow-up were found on physical and psychological HRQOL measures (16.4%-30.9%). A higher proportion of the veteran caregiver group had clinically elevated scores on nine measures at baseline and seven measures at follow-up. Examining the number of clinically elevated scores simultaneously across all 17 measures, the service member caregiver group had multiple elevated scores (e.g., 4 or more: baseline = 25.5%, follow-up = 27.3%). A higher proportion of the veteran caregiver group had multiple clinically elevated scores for 13 comparisons at baseline (h = .35-.82), but reduced to eight comparisons at follow-up (h = .36-.63). In the service member caregiver group, the proportion of caregivers with clinically elevated scores at baseline and follow-up was equally dispersed across persistent and newly developed symptoms, but higher for persistent symptoms compared to developed symptoms in the veteran caregiver group. CONCLUSIONS: Many caregivers of service members reported clinically elevated scores across HRQOL domains and the prevalence increased over 2 years. More services for caregivers in the Department of Defense may be helpful in reducing the trajectory of newly developed symptoms long term. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

11.
Sci Rep ; 14(1): 13685, 2024 06 13.
Article in English | MEDLINE | ID: mdl-38871776

ABSTRACT

Low-grade chronic inflammation is associated with many age-related conditions. Non-invasive methods to monitor low-grade chronic inflammation may improve the management of older people at risk of poorer outcomes. This longitudinal cohort study has determined baseline inflammation using neopterin volatility in monthly urine samples of 45 independent older adults (aged 65-75 years). Measurement of neopterin, an inflammatory metabolite, enabled stratification of individuals into risk categories based on how often in a 12-month period their neopterin level was raised. Hearing was measured (pure-tone audiometry) at baseline, 1 year and 3 years of the study. Results show that those in the highest risk category (neopterin raised greater than 50% of the time) saw greater deterioration, particularly in high-frequency, hearing. A one-way Welch's ANOVA showed a significant difference between the risk categories for change in high-frequency hearing (W (3, 19.6) = 9.164, p = 0.0005). Despite the study size and duration individuals in the highest risk category were more than twice as likely to have an additional age-related morbidity than those in the lowest risk category. We conclude that volatility of neopterin in urine may enable stratification of those at greatest risk of progression of hearing loss.


Subject(s)
Neopterin , Humans , Neopterin/urine , Aged , Male , Female , Longitudinal Studies , Hearing Loss/urine , Audiometry, Pure-Tone , Biomarkers/urine , Auditory Threshold , Inflammation/urine
12.
PLoS Pathog ; 20(6): e1012177, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38843296

ABSTRACT

BACKGROUND: Epstein-Barr virus (EBV) is a likely prerequisite for multiple sclerosis (MS) but the underlying mechanisms are unknown. We investigated antibody and T cell responses to EBV in persons with MS (pwMS), healthy EBV-seropositive controls (HC) and post-infectious mononucleosis (POST-IM) individuals up to 6 months after disease resolution. The ability of EBV-specific T cell responses to target antigens from the central nervous system (CNS) was also investigated. METHODS: Untreated persons with relapsing-remitting MS, POST-IM individuals and HC were, as far as possible, matched for gender, age and HLA-DRB1*15:01. EBV load was determined by qPCR, and IgG responses to key EBV antigens were determined by ELISA, immunofluorescence and Western blot, and tetanus toxoid antibody responses by multiplex bead array. EBV-specific T cell responses were determined ex vivo by intracellular cytokine staining (ICS) and cross-reactivity of in vitro-expanded responses probed against 9 novel Modified Vaccinia Ankara (MVA) viruses expressing candidate CNS autoantigens. RESULTS: EBV load in peripheral blood mononuclear cells (PBMC) was unchanged in pwMS compared to HC. Serologically, while tetanus toxoid responses were unchanged between groups, IgG responses to EBNA1 and virus capsid antigen (VCA) were significantly elevated (EBNA1 p = 0.0079, VCA p = 0.0298) but, importantly, IgG responses to EBNA2 and the EBNA3 family antigens were also more frequently detected in pwMS (EBNA2 p = 0.042 and EBNA3 p = 0.005). In ex vivo assays, T cell responses to autologous EBV-transformed B cells and to EBNA1 were largely unchanged numerically, but significantly increased IL-2 production was observed in response to certain stimuli in pwMS. EBV-specific polyclonal T cell lines from both MS and HC showed high levels of autoantigen recognition by ICS, and several neuronal proteins emerged as common targets including MOG, MBP, PLP and MOBP. DISCUSSION: Elevated serum EBV-specific antibody responses in the MS group were found to extend beyond EBNA1, suggesting a larger dysregulation of EBV-specific antibody responses than previously recognised. Differences in T cell responses to EBV were more difficult to discern, however stimulating EBV-expanded polyclonal T cell lines with 9 candidate CNS autoantigens revealed a high level of autoreactivity and indicate a far-reaching ability of the virus-induced T cell compartment to damage the CNS.


Subject(s)
Antibodies, Viral , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Humans , Herpesvirus 4, Human/immunology , Female , Male , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/virology , Adult , Antibodies, Viral/immunology , Middle Aged , Cross Reactions/immunology , Multiple Sclerosis/immunology , Multiple Sclerosis/virology , T-Lymphocytes/immunology , Multiple Sclerosis, Relapsing-Remitting/immunology , Multiple Sclerosis, Relapsing-Remitting/virology , Antigens, Viral/immunology , Viral Load , Infectious Mononucleosis/immunology , Infectious Mononucleosis/virology , Epstein-Barr Virus Nuclear Antigens/immunology , Immunoglobulin G/immunology
13.
Haematologica ; 2024 May 30.
Article in English | MEDLINE | ID: mdl-38813748

ABSTRACT

T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of paediatric and 50% of adult T-ALL patients have refractory disease or relapse and die from the disease. To improve patient outcome new therapeutics are needed. With the aim to identify new therapeutic targets, we combined the analysis of T-ALL gene expression and metabolism to identify the metabolic adaptations that T-ALL cells exhibit. We found that glutamine uptake is essential for T-ALL proliferation. Isotope tracing experiments showed that glutamine fuels aspartate synthesis through the TCA cycle and that glutamine and glutamine-derived aspartate together supply three nitrogen atoms in purines and all but one atom in pyrimidine rings. We show that the glutamate-aspartate transporter EAAT1 (SLC1A3), which is normally expressed in the central nervous system, is crucial for glutamine conversion to aspartate and nucleotides and that T-ALL cell proliferation depends on EAAT1 function. Through this work, we identify EAAT1 as a novel therapeutic target for T-ALL treatment.

14.
Sex Reprod Healthc ; 40: 100978, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38703456

ABSTRACT

AIM: To understand the maternity experiences of women from minority ethnic groups who had given birth in an NHS trust in the North-West of England, and experiences of midwives caring for them. BACKGROUND: Women from minority ethnic groups have poorer maternity outcomes compared with other women. Research about maternity experiences of women from minority ethnic groups is limited but suggests that they have poorer experiences. METHOD: Constructivist grounded theory was used as the framework for the study. Thirteen women and sixteen midwives were interviewed to elicit views and maternity experiences of women from minority ethnic groups. Interviews were transcribed, analysed, and focused codes developed into theoretical codes resulting in an emergent grounded theory. FINDINGS: Four sub-categories emerged: 'I was feeling protected', 'it is just literally empowering them, 'it will affect them more', and 'if people speak out it will help other people'. These sub-categories generated a substantive theory: 'striving towards equity and women centred care'. DISCUSSION: Culturally sensitive, relational care made women feel safe and trust their care providers. Information provision led to reassurance and enabled women to make choices about their care. Midwives' workload compromised care provision and disproportionally affected women from minority ethnic groups, especially those who do not speak English. Women from minority groups are less likely to complain and be represented in feedback. CONCLUSION: Culturally sensitive care is meeting the individual needs of many women; however, non- English speakers are disproportionally and negatively affected by midwives' workload, attitudes, or service challenges, reducing their reassurance and choice.


Subject(s)
Ethnicity , Grounded Theory , Maternal Health Services , Midwifery , Humans , Female , England , Pregnancy , Adult , Minority Groups/psychology , Qualitative Research , Ethnic and Racial Minorities , Culturally Competent Care , Patient Satisfaction/ethnology , Attitude of Health Personnel , Trust
15.
J Marital Fam Ther ; 50(3): 523-544, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38773715

ABSTRACT

Widespread political polarization throughout the United States is a threat to the time-honored democratic tradition of utilizing civil discussion and respectful debate to express divergent views and strive for common ground. The political differences that divide us now are so deep and rife with toxic emotion that they threaten to undermine our social well-being at both the micro and macro levels. While family therapists are trained to work with relational tensions and to help family members to constructively negotiate their differences, the severity of the hostility and resentment tied to divergent political orientations has made this work increasingly difficult to achieve. This article explores how family therapy training programs can help trainees deepen their capacity for constructive political dialoguing that includes learning how to effectively manage their reactivity to those whose values and views may be dramatically different from their own so that they can support clients in doing the same.


Subject(s)
Family Therapy , Humans , Family Therapy/education , United States , Politics , Adult
16.
J Affect Disord ; 358: 408-415, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38705525

ABSTRACT

BACKGROUND: The purpose of this cross-sectional study was to examine the influence of subthreshold posttraumatic stress disorder (PTSD) and full PTSD on quality of life following mild traumatic brain injury (mTBI). METHODS: Participants were 734 service members and veterans (SMV) classified into two injury groups: uncomplicated mild TBI (MTBI; n = 596) and injured controls (IC, n = 139). Participants completed a battery of neurobehavioral measures, 12-or-more months post-injury, that included the PTSD Checklist Civilian version, Neurobehavioral Symptom Inventory, and select scales from the TBI-QOL and MPAI. The MTBI group was divided into three PTSD subgroups: No-PTSD (n = 266), Subthreshold PTSD (n = 139), and Full-PTSD (n = 190). RESULTS: There was a linear relationship between PTSD severity and neurobehavioral functioning/quality of life in the MTBI sample. As PTSD severity increased, significantly worse scores were found on 11 of the 12 measures (i.e. , MTBI: Full-PTSD > Sub-PTSD > No-PTSD). When considering the number of clinically elevated scores, a linear relationship between PTSD severity and neurobehavioral functioning/quality of life was again observed in the MTBI sample (e.g., 3-or-more elevated scores: Full-PTSD = 92.1 %, Sub-PTSD = 61.9 %, No-PTSD = 19.9 %). LIMITATIONS: Limitations included the use of a self-report measure to determine diagnostic status that may under/overcount or mischaracterize individuals. CONCLUSION: PTSD symptoms, whether at the level of diagnosable PTSD, or falling short of that because of the intensity or characterization of symptoms, have a significant negative impact on one's quality of life following MTBI. Clinicians' treatment targets should focus on the symptoms that are most troubling for an individual and the individual's perception of quality of life, regardless of the diagnosis itself.


Subject(s)
Military Personnel , Quality of Life , Stress Disorders, Post-Traumatic , Veterans , Humans , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/psychology , Veterans/psychology , Veterans/statistics & numerical data , Male , Quality of Life/psychology , Adult , Female , Cross-Sectional Studies , Military Personnel/psychology , Military Personnel/statistics & numerical data , United States , Middle Aged , Severity of Illness Index , Brain Concussion/psychology , Brain Concussion/diagnosis , Brain Injuries, Traumatic/psychology , Neuropsychological Tests/statistics & numerical data , Clinical Relevance
17.
BMJ Open ; 14(5): e082350, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806433

ABSTRACT

INTRODUCTION: Radiologist shortages threaten the sustainability of breast cancer screening programmes. Artificial intelligence (AI) products that can interpret mammograms could mitigate this risk. While previous studies have suggested this technology has accuracy comparable to radiologists most have been limited by using 'enriched' datasets and/or not considering the interaction between the algorithm and human readers. This study will address these limitations by comparing the accuracy of a workflow using AI alongside radiologists on a large consecutive cohort of examinations from a breast cancer screening programme. The study will combine the strengths of a large retrospective design with the benefit of prospective data collection. It will test this technology without risk to screening programme participants nor the need to wait for follow-up data. With a sample of 2 years of consecutive screening examinations, it is likely the largest test of this technology to date. The study will help determine whether this technology can safely be introduced into the BreastScreen New South Wales (NSW) population-based screening programme to address radiology workforce risks without compromising cancer detection rates or increasing false-positive recalls. METHODS AND ANALYSIS: A retrospective, consecutive cohort of digital mammography screens from 658 207 examinations from BreastScreen NSW will be reinterpreted by the Lunit Insight MMG AI product. The cohort includes 4383 screen-detected and 1171 interval cancers. The results will be compared with radiologist single reading and the AI results will also be used to replace the second reader in a double-reading model. New adjudication reading will be performed where the AI disagrees with the first reader. Recall rates and cancer detection rates of combined AI-radiologist reading will be compared with the rates obtained at the time of screening. ETHICS AND DISSEMINATION: This study has ethical approval from the NSW Health Population Health Services Research Ethics Committee (2022/ETH02397). Findings will be published in peer-reviewed journals and presented at conferences. The findings of this evaluation will be provided to programme managers, governance bodies and other stakeholders in Australian breast cancer screening programmes.


Subject(s)
Artificial Intelligence , Breast Neoplasms , Early Detection of Cancer , Mammography , Humans , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/diagnosis , Female , Mammography/methods , New South Wales , Early Detection of Cancer/methods , Retrospective Studies , Mass Screening/methods , Middle Aged , Research Design
18.
Int J Mol Sci ; 25(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38732071

ABSTRACT

Iron regulatory proteins (IRP1 and IRP2) are the master regulators of mammalian iron homeostasis. They bind to the iron-responsive elements (IREs) of the transcripts of iron-related genes to regulate their expression, thereby maintaining cellular iron availability. The primary method to measure the IRE-binding activity of IRPs is the electrophoresis mobility shift assay (EMSA). This method is particularly useful for evaluating IRP1 activity, since IRP1 is a bifunctional enzyme and its protein levels remain similar during conversion between the IRE-binding protein and cytosolic aconitase forms. Here, we exploited a method of using a biotinylated-IRE probe to separate IRE-binding IRPs followed by immunoblotting to analyze the IRE-binding activity. This method allows for the successful measurement of IRP activity in cultured cells and mouse tissues under various iron conditions. By separating IRE-binding IRPs from the rest of the lysates, this method increases the specificity of IRP antibodies and verifies whether a band represents an IRP, thereby revealing some previously unrecognized information about IRPs. With this method, we showed that the S711-phosphorylated IRP1 was found only in the IRE-binding form in PMA-treated Hep3B cells. Second, we found a truncated IRE-binding IRP2 isoform that is generated by proteolytic cleavage on sites in the 73aa insert region of the IRP2 protein. Third, we found that higher levels of SDS, compared to 1-2% SDS in regular loading buffer, could dramatically increase the band intensity of IRPs in immunoblots, especially in HL-60 cells. Fourth, we found that the addition of SDS or LDS to cell lysates activated protein degradation at 37 °C or room temperature, especially in HL-60 cell lysates. As this method is more practical, sensitive, and cost-effective, we believe that its application will enhance future research on iron regulation and metabolism.


Subject(s)
Iron Regulatory Protein 1 , Iron , Humans , Animals , Iron/metabolism , Iron Regulatory Protein 1/metabolism , Iron Regulatory Protein 1/genetics , Mice , Iron Regulatory Protein 2/metabolism , Iron Regulatory Protein 2/genetics , Biotinylation , Response Elements , Phosphorylation , Iron-Regulatory Proteins/metabolism , Iron-Regulatory Proteins/genetics , Protein Binding , Cell Line, Tumor
19.
Rehabil Psychol ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780581

ABSTRACT

OBJECTIVE: The purpose of this study was to (a) identify the prevalence and barriers of self-reported service needs in a military sample with and without traumatic brain injury (TBI), (b) evaluate the influence of the number of service needs on overall neurobehavioral functioning, and (c) examine the longitudinal trajectories of service needs over time. METHOD: Participants were 941 U.S. service members and veterans (SMVs) prospectively enrolled into four groups: uncomplicated mild TBI (MTBI; n = 455); complicated mild, moderate, severe, and penetrating TBI combined (STBI; n = 164); injured controls (IC, n = 138); and noninjured controls (NIC, n = 184). Participants completed a battery of neurobehavioral measures, as well as a self-reported service need interview, 12 or more month's postinjury. In addition, a longitudinal cohort (n = 553) was included using a subset of participants who had completed two or more evaluations. RESULTS: When examining the total number of self-reported service needs, there was a greater proportion of the MTBI and STBI groups that had a higher number of service needs compared to the NIC and IC groups (p < .001). In the MTBI and STBI groups, as the number of service needs increased, worse scores were found on all neurobehavioral measures. In the longitudinal cohort, the STBI group reported the highest number of service needs that persisted or developed over time (six needs), followed by the MTBI (three needs), IC (one need), and NIC (zero need) groups. CONCLUSIONS: These findings call for the need to enhance the provision of information given to service members and veterans following TBI regarding available services. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

20.
Biochim Biophys Acta Mol Cell Res ; 1871(5): 119723, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38599324

ABSTRACT

Viruses have evolved complex mechanisms to exploit host factors for replication and assembly. In response, host cells have developed strategies to block viruses, engaging in a continuous co-evolutionary battle. This dynamic interaction often revolves around the competition for essential resources necessary for both host cell and virus replication. Notably, iron, required for the biosynthesis of several cofactors, including iron­sulfur (FeS) clusters, represents a critical element in the ongoing competition for resources between infectious agents and host. Although several recent studies have identified FeS cofactors at the core of virus replication machineries, our understanding of their specific roles and the cellular processes responsible for their incorporation into viral proteins remains limited. This review aims to consolidate our current knowledge of viral components that have been characterized as FeS proteins and elucidate how viruses harness these versatile cofactors to their benefit. Its objective is also to propose that viruses may depend on incorporation of FeS cofactors more extensively than is currently known. This has the potential to revolutionize our understanding of viral replication, thereby carrying significant implications for the development of strategies to target infections.


Subject(s)
Iron-Sulfur Proteins , Viral Proteins , Virus Replication , Iron-Sulfur Proteins/metabolism , Iron-Sulfur Proteins/genetics , Humans , Viral Proteins/metabolism , Viral Proteins/genetics , Viruses/metabolism , Viruses/genetics , Virus Diseases/metabolism , Virus Diseases/virology , Iron/metabolism , Animals , Host-Pathogen Interactions
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