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Background Text message-delivered interventions have potential to prevent weight regain and maintain diet and physical activity behaviours through extending contact with participants following initial weight loss, lifestyle interventions. Using the RE-AIM Framework, this study evaluated the adoption, reach, implementation, effectiveness, and maintenance of an extended contact text-message intervention following the Healthy Living after Cancer (HLaC) program. HLaC was a 6-month, telephone-delivered intervention targeting healthy diet, physical activity and weight loss for adult cancer survivors, offered by Cancer Councils (CCs) in Australia. Methods HLaC completers ( n  = 182) were offered extended contact via text messages for 6-months (HLaC+Txt). Text message content/frequency was individually tailored to participant’s preferences, ascertained through two telephone-tailoring interviews with CC staff. Adoption (HLaC+Txt uptake among eligible CCs), reach (uptake by HLaC completers) and implementation (intervention cost/length; text dose) were assessed. The effectiveness of extended contact relative to historic controls was quantified by pre-to-post HLaC+Txt changes in self-reported: weight, moderate-vigorous physical activity (MVPA), fruit and vegetable intake, fat and fibre behaviour. Maintenance, following 6-months of noncontact for the intervention cohort, was assessed for these same variables. Semi-structured interviews with CC staff and participants contextualised outcomes. Results HLaC+Txt was adopted by all four CCs who had delivered HLaC. In total, 115 participants commenced HLaC+Txt, with reach ranging across CCs from 47 to 80% of eligible participants. The mean number of weeks participants received the text message intervention ranged across CCs from 18.5–22.2 weeks. Participants received (median, 25th,75th percentile) 83 (48, 119) texts, ranging across CCs from 40 to 112. The total cost of HLaC+Txt delivery was on average $AUD85.00/participant. No meaningful ( p  < 0.05) differences in self-reported outcomes were seen between HLaC+Txt and control cohorts. After 6-months no contact the intervention cohort had maintained weight, fruit intake, fat and fibre index scores relative to end of HLaC+Txt outcomes. Participants/CC staff perceived an important intervention component was maintaining accountability. Conclusions While feasible to implement, HLaC+Txt was not effective in the short term. However, intervention effects during the non-contact period suggest the program supports longer term maintenance of weight and diet behaviour. Intervention delivery in this real-world context highlighted key considerations for future implementation. Trial registration Australian and New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12615000882527 (registered on 24/08/2015).

Background Obesity, physical inactivity and poor diet quality have been associated with increased risk of breast cancer-specific and all-cause mortality as well as treatment-related side-effects in breast cancer survivors. Weight loss intervention trials in breast cancer survivors have shown that weight loss is safe and achievable; however, few studies have examined the benefits of such interventions on a broad range of outcomes and few have examined factors important to translation (e.g. feasible delivery method for scaling up, assessment of sustained changes, cost-effectiveness). The Living Well after Breast Cancer randomized controlled trial aims to evaluate a 12-month telephone-delivered weight loss intervention (versus usual care) on weight change and a range of secondary outcomes including cost-effectiveness. Methods/design Women (18–75 years; body mass index 25–45 kg/m 2 ) diagnosed with stage I-III breast cancer in the previous 2 years are recruited from public and private hospitals and through the state-based cancer registry (target n  = 156). Following baseline assessment, participants are randomized 1:1 to either a 12-month telephone-delivered weight loss intervention (targeting diet and physical activity) or usual care. Data are collected at baseline, 6-months (mid-intervention), 12-months (end-of-intervention) and 18-months (maintenance). The primary outcome is change in weight at 12-months. Secondary outcomes are changes in body composition, bone mineral density, cardio-metabolic and cancer-related biomarkers, metabolic health and chronic disease risk, physical function, patient-reported outcomes (quality of life, fatigue, menopausal symptoms, body image, fear of cancer recurrence) and behaviors (dietary intake, physical activity, sitting time). Data collected at 18-months will be used to assess whether outcomes achieved at end-of-intervention are sustained six months after intervention completion. Cost-effectiveness will be assessed, as will mediators and moderators of intervention effects. Discussion This trial will provide evidence needed to inform the wide-scale provision of weight loss, physical activity and dietary interventions as part of routine survivorship care for breast cancer survivors. Trial registration Australian and New Zealand Clinical Trial Registry (ANZCTR) - ACTRN12612000997853 (Registered 18 September 2012).

Extending contact with participants after the end of an initial weight loss intervention has been shown to lead to maintained weight loss and related behavioral change. Mobile phone text messaging (short message service, SMS) offers a low-cost and efficacious method to deliver extended contact. In this rapidly developing area, formative work is required to understand user perspectives of text message technology. An extended contact intervention delivered by text messages following an initial telephone-delivered weight loss intervention in breast cancer survivors provided this opportunity. The aim of this study was to qualitatively explore women's perceptions of participation in an extended contact intervention using text messaging to support long-term weight loss, physical activity, and dietary behavioral change. Following the end of an initial 6-month randomized controlled trial of a telephone-delivered weight loss intervention (versus usual care), participants received a 6-month extended contact intervention via tailored text messages. Participant perceptions of the different types of text messages, the content, tailoring, timing, and frequency of the text messages, and the length of the intervention were assessed through semistructured interviews conducted after the extended contact intervention. The interviews were transcribed verbatim and analyzed with key themes identified. Participants (n=27) were a mean age of 56.0 years (SD 7.8) and mean body mass index of 30.4 kg/m2 (SD 4.2) and were at a mean of 16.1 months (SD 3.1) postdiagnosis at study baseline. Participants perceived the text messages to be useful behavioral prompts and felt the messages kept them accountable to their behavioral change goals. The individual tailoring of the text message content and schedules was a key to the acceptability of the messages; however, some women preferred the support and real-time discussion via telephone calls (during the initial intervention) compared with the text messages (during the extended contact intervention). Text message support was perceived as acceptable for the majority of women as a way of extending intervention contact for weight loss and behavioral maintenance. Text messages supported the maintenance of healthy behaviors established in the intervention phase and kept the women accountable to their goals. A combination of telephone calls and text message support was suggested as a more acceptable option for some of the women for an extended contact intervention.

DNA replication occurs through an intricately regulated series of molecular events and is fundamental for genome stability 1 , 2 . At present, it is unknown how the locations of replication origins are determined in the human genome. Here we dissect the role of topologically associating domains (TADs) 3 – 6 , subTADs 7 and loops 8 in the positioning of replication initiation zones (IZs). We stratify TADs and subTADs by the presence of corner-dots indicative of loops and the orientation of CTCF motifs. We find that high-efficiency, early replicating IZs localize to boundaries between adjacent corner-dot TADs anchored by high-density arrays of divergently and convergently oriented CTCF motifs. By contrast, low-efficiency IZs localize to weaker dotless boundaries. Following ablation of cohesin-mediated loop extrusion during G1, high-efficiency IZs become diffuse and delocalized at boundaries with complex CTCF motif orientations. Moreover, G1 knockdown of the cohesin unloading factor WAPL results in gained long-range loops and narrowed localization of IZs at the same boundaries. Finally, targeted deletion or insertion of specific boundaries causes local replication timing shifts consistent with IZ loss or gain, respectively. Our data support a model in which cohesin-mediated loop extrusion and stalling at a subset of genetically encoded TAD and subTAD boundaries is an essential determinant of the locations of replication origins in human S phase. A study shows that the three-dimensional conformation of the human genome influences the positioning of DNA replication initiation zones, highlighting cohesin-mediated loop anchors as essential determinants of their precise location.

Nuclear actin-based movements have been shown to orchestrate clustering of DNA double-strand breaks (DSBs) into homology-directed repair domains. Here we describe multiscale three-dimensional genome reorganization following DNA damage and analyze the contribution of the nuclear WASP-ARP2/3-actin pathway toward chromatin topology alterations and pathologic repair. Hi-C analysis reveals genome-wide, DNA damage-induced chromatin compartment flips facilitated by ARP2/3 that enrich for open, A compartments. Damage promotes interactions between DSBs, which in turn facilitate aberrant, actin-dependent intra- and inter-chromosomal rearrangements. Our work establishes that clustering of resected DSBs into repair domains by nuclear actin assembly is coordinated with multiscale alterations in genome architecture that enable homology-directed repair while also increasing nonhomologous end-joining-dependent translocation frequency. Here the authors report a genomic view of 3D chromatin reorganization following DNA damage. Movement of damaged DNA into nuclear domains, which is brought about by nuclear actin, favors error-free damage repair at the expense of rare chromosome rearrangements with oncogenic potential.

We conducted a retrospective genomic surveillance study of St. Louis encephalitis virus (SLEV) in Texas, USA, to determine the genotypes circulating in the region. By using a custom tiled-amplicon assay with Oxford Nanopore sequencing, we generated 63 genomes from SLEV-positive mosquito pools and viral isolates collected during 2009-2024. Phylogenomic analysis revealed temporal overlap of genotype II and III circulation, but with distinct geographic segregation. Genotype II was confined to Gulf Coast counties with sustained local transmission, whereas genotype III was only in north and west Texas, but with persistent circulation and repeated introductions. We identified the earliest known US genotype III sequences, although their phylogenetic placement leaves the entry point of genotype III into the United States unresolved. Our findings emphasize the need for clinical vigilance in West Texas, where SLEV and West Nile virus co-circulate, and suggest the Gulf Coast may be buffered against foreign genotype introduction.

Importance Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. Objective To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. Design, Setting, and Participants This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. Exposure Respiratory syncytial virus. Main Outcomes and Measures Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. Results The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. Conclusions and Relevance In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.

The Global Flourishing Study is a longitudinal panel study of over 200,000 participants in 22 geographically and culturally diverse countries, spanning all six populated continents, with nationally representative sampling and intended annual survey data collection for 5 years to assess numerous aspects of flourishing and its possible determinants. The study is intended to expand our knowledge of the distribution and determinants of flourishing around the world. Relations between a composite flourishing index and numerous demographic characteristics are reported. Participants were also surveyed about their childhood experiences, which were analyzed to determine their associations with subsequent adult flourishing. Analyses are presented both across and within countries, and discussion is given as to how the demographic and childhood relationships vary by country and which patterns appear to be universal versus culturally specific. Brief comment is also given on the results of a whole series of papers in the Global Flourishing Study Special Collection, employing similar analyses, but with more-specific aspects of well-being. The Global Flourishing Study expands our knowledge of the distribution and determinants of well-being and provides foundational knowledge for the promotion of societal flourishing. The Global Flourishing Study provides a comprehensive view of the distribution and determinants of well-being by assessing domains such as health, happiness, meaning, character, relationships and financial security. Initial findings reveal significant variations in flourishing across countries and demographic groups, with factors such as age, marital status and religious service attendance showing strong associations with well-being.

ObjectivesAssess the feasibility of a mobile health (mHealth)-supported home-delivered physical activity (PA) intervention (MOTIVATE-T2D) in people with recently diagnosed type 2 diabetes (T2D).DesignFeasibility multicentre, parallel group, randomised controlled trial (RCT).SettingParticipants were recruited from England and Canada using a decentralised design.ParticipantsAdults (40–75 years) recently diagnosed with T2D (5–24 months).InterventionsParticipants were randomised 1:1 to intervention (MOTIVATE-T2D) or active control groups. Participants codesigned 6month- home-delivered, personalised, progressive PA programmes supported by virtual behavioural counselling. MOTIVATE-T2D used biofeedback from wearable technologies to support the programme. The active control group received the same intervention without wearables.OutcomesThe primary outcomes were recruitment rate, retention and adherence to purposeful exercise. Clinical data on effectiveness were collected as exploratory outcomes at baseline, 6 and 12 months, with HbA1c and systolic blood pressure (BP) proposed as primary outcomes for a future full RCT.Resultsn=135 eligible participants expressed an interest in the trial, resulting in 125 participants randomised (age 55±9 years, 48% female, 81% white), a recruitment rate of 93%. Retention at 12 months was 82%. MOTIVATE-T2D participants were more likely to start (OR 10.4, CI 3.4 to 32.1) and maintain purposeful exercise at 6 (OR 7.1, CI 3.2 to 15.7) and 12 months (OR 2.9, CI 1.2 to 7.4). Exploratory clinical outcomes showed a potential effect in favour of MOTIVATE-T2D, including proposed primary outcomes HbA1c and systolic BP (between-group mean differences: HbA1c: 6 months: −5% change from baseline, CI −10 to 2: 12 months: −2% change from baseline, CI −8 to −4; systolic BP: 6 months: −1 mm Hg, CI −5 to 3: 12 months: −4 mm Hg, CI −8 to 1).ConclusionsOur findings support the feasibility of delivering the MOTIVATE-T2D mHealth-supported PA intervention for people with recently diagnosed T2D and progression to a full RCT to examine its clinical and cost-effectiveness.Trial registration numberISRCTN: 14335124; ClinicalTrials.gov: NCT0465353.

Repeated exposure to the opioid agonist, oxycodone, can lead to addiction. Here, we sought to identify potential neurobiological consequences of withdrawal from escalated and non-escalated oxycodone self-administration in rats. To reach these goals, we used short-access (ShA) (3 h) and long-access (LgA) (9 h) exposure to oxycodone self-administration followed by protracted forced abstinence. After 31 days of withdrawal, we quantified mRNA and protein levels of opioid receptors in the rat dorsal striatum and hippocampus. Rats in the LgA, but not the ShA, group exhibited escalation of oxycodone SA, with distinction of two behavioral phenotypes of relatively lower (LgA-L) and higher (LgA-H) oxycodone takers. Both LgA, but not ShA, phenotypes showed time-dependent increases in oxycodone seeking during the 31 days of forced abstinence. Rats from both LgA-L and LgA-H groups also exhibited decreased levels of striatal mu opioid receptor protein levels in comparison to saline and ShA rats. In contrast, mu opioid receptor mRNA expression was increased in the dorsal striatum of LgA-H rats. Moreover, hippocampal mu and kappa receptor protein levels were both increased in the LgA-H phenotype. Nevertheless, hippocampal mu receptor mRNA levels were decreased in the two LgA groups whereas kappa receptor mRNA expression was decreased in ShA and LgA oxycodone groups. Decreases in striatal mu opioid receptor protein expression in the LgA rats may serve as substrates for relapse to drug seeking because these changes occur in rats that showed incubation of oxycodone seeking.