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Hawraa Ali-Jerman,1 Zainab Al-Quraishi,1 Ashish Muglikar,1 Yvonne Perrie,1 Rothwelle J Tate,1 Margaret Mullin,2 Gayle McNeill,1 Graeme Mackenzie,1 Christine Dufès1 1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK; 2Cell Analysis Facility, Medical and Veterinary & Life Sciences Shared Research Facilities, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UKCorrespondence: Christine Dufès, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK, Tel +44 1415483796, Fax +44 1415522562, Email C.Dufes@strath.ac.ukBackground: Gene therapy is a promising therapeutic approach for treating various disorders by introducing modified nucleic acids to correct cellular dysfunctions or introduce new functions. Despite significant advancements in the field, the effective delivery of nucleic acids remains a challenge, due to biological barriers and the immune system’s ability to target and destroy these molecules. Due to their branched structure and ability to condense negatively charged nucleic acids, cationic dendrimers have shown potential in overcoming these challenges. Despite this, standardized scalable production methods are still lacking. This study investigates the use of microfluidics to formulate generation 3-diaminobutyric polypropylenimine (DAB) dendriplexes and compares their characteristics and in vitro gene delivery efficacy to those prepared using conventional manual mixing.Methods: DAB dendriplexes were produced by both microfluidic and manual approaches and characterized. Their cellular uptake and gene expression were evaluated on C6 glioma cancer cells in vitro.Results: Dendriplexes formed using microfluidics at the optimal flow rate and ratio demonstrated enhanced DNA condensation over time, achieving up to 97% condensation at 24 hours. Both preparation methods produced positively charged dendriplexes, indicating stable formulations. However, dendriplexes prepared through hand mixing resulted in smaller particle sizes, significantly higher cellular uptake and gene expression efficacy compared to those prepared by microfluidics. Nonetheless, microfluidic preparation offers the advantage of standardized and scalable production, which is essential for future applications.Conclusion: This study highlights the potential of microfluidic technology to improve precision and scalability in gene delivery, paving the way for future advancements in gene therapy. Our findings suggest that, with further optimization, microfluidic systems could provide superior control over dendriplex formation, expanding their potential use in gene therapy applications. Keywords: polypropylenimine dendrimer, dendriplex, glioma, microfluidics, cellular uptake, transfection

Introduction: This study aimed to systematically identify the environmental factors that impacted people with disability during the COVID-19 pandemic. Methods: A scoping literature review was conducted using LitCOVID (January 1–July 31, 2020). Sixty-six articles met the inclusion criteria that (1) discussed disability and/or health conditions related to functioning and (2) considered environmental factors. A qualitative content analysis was conducted using codes from the WHO International Classification of Functioning, Disability and Health. Results: A total of 212 International Classification of Functioning, Disability and Health codes were used in the coding process. The most frequent codes referred to health services policies and public health guidelines. These policies, although generally considered facilitators for minimizing infection, were frequently identified as barriers to the health, participation, and human rights of people with disability. The lack of disability-specific population data was identified as a key barrier to planning and decision making. Conclusions: The social determinants of health for people with disability were not adequately considered in the acute phase of infection prevention at the population level. Integrating the International Classification of Functioning, Disability and Health in emergency management provides a tool to evaluate functioning and address barriers for those in need.

Copper (Cu) is typically adequate at 0.5 μM (0.03 ppm) in hydroponics and at 2 μM (0.125 ppm) in soilless media, but elevated levels can be used to inhibit pathogenic fungal growth. We studied the effect of elevated Cu on the growth of lettuce and tomato in peat-based media and deep-flow hydroponics. Lettuce growth in hydroponics was not hindered until a concentration greater than 4 μM (0.25 ppm) Cu was used, which is eight times greater than the adequate level. Tomato was more tolerant of elevated Cu, with no growth suppression up to 8 μM (0.5 ppm) in hydroponics. Organic matter tightly binds Cu, and bioavailability is thus determined by organic components in soilless media. We confirmed an adsorption capacity of 19 mg Cu per g of peat, which explains why there was no inhibition of lettuce or tomato growth up to 1000 μM (64 ppm) Cu in peat-based media. When chelated with ethylenediaminetetraacetic acid, Cu binding to organic matter was reduced and growth was decreased in lettuce but not tomato. Both species tolerated a 100-fold greater concentration of Cu in peat-based media than in deep-flow hydroponics. Elevated Cu in solution increased concentrations 20 times greater in root tissue than in leaves. These solution and tissue concentrations are greater than identified toxicity thresholds of pathogenic fungal and fungal-like organisms, and could thus be used to suppress root-borne fungal and fungal-like diseases.

Silicon (Si) is a beneficial element that is usually ample in mineral soil solution, but it is minimally bioavailable from soilless substrates. Several Si additives are commercially available, but the rate of dissolution of Si is not well-characterized. The ideal additive would steadily release bioavailable Si over the crop lifecycle. We report the long-term (120 days) dissolution of Si from soilless substrates and substrate additives. Studies involving gently agitated containers with deionized water indicated that perlite, sphagnum peat, vermiculite, and coconut coir released less than 0.03 mmol Si per liter of substrate per day. Rice hulls and wollastonite (CaSiO3) had 7- to 130-times faster rates of dissolution in this system; therefore, they were further studied in peat-based media. Dissolution of Si from the addition of 1 g wollastonite per liter of peat peaked at day 10 at 2.1 mmol Si per liter of media per leaching event (15% by volume); then, it gradually decreased over 120 days. The peak dissolution of Si amended with 12% rice hulls was similar, but it gradually increased over time. The concentrations of nine heavy metals in plant tissue were compared with untreated control plants to determine wollastonite and steel slag. The concentration of some elements statistically increased, but all concentrations were well below the legal concentration limits of these elements for human consumption in the United States. These results indicate that both wollastonite and rice hulls steadily release Si for up to 4 months; therefore, they are good sources of Si for container-grown crops in soilless media.

Jitkasem Meewan,1 Sukrut Somani,1 Jamal Almowalad,1 Partha Laskar,1 Margaret Mullin,2 Graeme MacKenzie,1 Swapnil Khadke,1 Yvonne Perrie,1 Christine Dufès1 1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK; 2Glasgow Imaging Facility, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UKCorrespondence: Christine Dufès, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, G4 0RE, UK, Tel +44 1415483796, Fax +44 1415522562, Email C.Dufes@strath.ac.ukBackground: The manufacture of nanoparticles using manual methods is hampered by its challenging scale-up and poor reproducibility. To overcome this issue, the production of zein nanoparticles entrapping a lipophilic drug model, coumarin-6, by using a microfluidic system was assessed in this study. The influence of PEG density and chain length on zein nanoparticle characteristics, as well as their uptake efficacy in melanoma cancer cells, was also evaluated.Methods: Zein nanoparticles were prepared by both manual and microfluidic approaches to allow comparison between the two processes. PEGylated zein nanoparticles with various PEG densities and chain lengths were produced by nanoprecipitation and characterized. Their cellular uptake was evaluated on B16F10 melanoma cancer cells in vitro.Results: Zein nanoparticles have successfully been produced by both manual and microfluidic approaches. Parameters such as total flow rate and flow rate ratio of the aqueous and organic phases in microfluidic process, as well as the method preparation and aqueous to organic phase volume ratio during nanoprecipitation, have been shown to strongly influence the characteristics of the resulting nanoparticles. Continuous microfluidics led to the production of nanoparticles with low yield and drug entrapment, unlike nanoprecipitation, which resulted in zein nanoparticles with an appropriate size and an optimal drug entrapment efficiency of 64%. The surface modification of the nanoparticles produced by nanoprecipitation, with lower PEG density and shorter PEG chain length made mPEG5K-zein (0.5:1) the most favorable formulation in our study, resulting in enhanced stability and higher coumarin-6 uptake by melanoma cancer cells.Conclusion: mPEG5K-zein (0.5:1) nanoparticles prepared by nanoprecipitation were the most promising formulation in our study, exhibiting increased stability and enhancing coumarin-6 uptake by melanoma cancer cells.Graphical Abstract: Keywords: zein nanoparticles, microfluidics, nanoprecipitation, poly(ethylene glycol), cellular uptake

Polarizable force fields crucially enhance the modeling of macromolecules in polar media. Here, we present new parameters to model six common monosaccharides with the polarizable AMOEBA force field. These parameters yield a thinner, but denser, hydration layer than that previously reported. This denser hydration layer results in eliminating non-physical aggregation of glucose in water—an issue that has plagued molecular dynamics simulations of carbohydrates for decades. [ABSTRACT FROM AUTHOR]

Research has found that many individuals who believe they have experienced discrimination do not report the incident to a relevant authority figure. Much of this research has focused on gender- and race-based discrimination, with relatively little research examining religion-based discrimination. Using data from a representative sample of U.S. adults, this research note examines the rate of reporting religious discrimination to authorities and the reasons given for non-reporting. Our analysis finds that only 13 percent of individuals perceiving religious discrimination report the experience to a relevant authority figure. The most common reason for non-reporting is a belief that nothing could be done, although the reasons given for non-reporting depend in part on the specific context or type of discrimination experienced. Moreover, relative to Christians, Muslims are significantly more likely to attribute their non-reporting to a belief that nothing could be done and a fear of personal risks. [ABSTRACT FROM AUTHOR]

Aim: The aim is to examine whether using a portable spring‐infusor device to deliver antibiotics compared with a standard infusion pump (SIP) translated to (i) improve health outcomes, (ii) reduce the length of stay (LoS), and (iii) reduce cost for treatment of exacerbations of cystic fibrosis (CF). Methods: An observational cohort study was conducted between December 2020 and June 2022 with participants aged 8–19 years admitted for exacerbation of CF. An activity monitor was fitted to participants to measure physical activities for the final 5 days of hospital admission. LoS was measured (days). Group allocation was according to participant preference. Costs were compared between the two groups for LoS, pump cost, and preparation and administration of antibiotics. Results:Twenty‐seven of 30 eligible participants were approached, and 22 consented. Data were captured for 16 participants (spring‐infusor n = 9): 10 female; mean (SD) age 14.5 (2.1) years. Average step count was negatively associated with age (rho = 0.50), and greater overall in participants using spring‐infusors (mean 5324 (SD 2873) steps) versus SIPs (4806 (3116) steps) ‐ mean (95% CI) increase in the spring‐infusor group of 3246 (54‐6438) for participants of the same age. LoS was longer on average in the SIP group, (mean (SD) LoS: 16.1 (4.3) versus 12.4 (1.7)). The estimated cost saving for a child using a spring‐infusor was AUS$12,000. Conclusion:Results from the study suggest that children hospitalised for exacerbations of CF are more active if they receive antibiotics via a spring‐infusor device compared with a SIP, and have reduced hospital stay that results in cost saving to the hospital. What is already known? Spring‐infusors are small, portable, and mechanical devices to deliver intravenous antibiotics to patients. Spring‐infusors are preferred by patients with CF at Perth Children's Hospital Physical activity in children with CF is recommended, including during hospital admissions to promote wellbeing, quality of life, and health outcomes. What this paper adds? Children hospitalised for exacerbations of CF may be more active if they receive antibiotics via a portable spring‐infusor device compared with a SIP. Children using spring‐infusors had reduced hospital stays that results in cost saving to the hospital. Children hospitalised for exacerbations of CF step on average, fewer than 5000 steps per day, which is well below recommendations. [ABSTRACT FROM AUTHOR]

Background: Nigerian pregnant and lactating women continue to experience high rates of malnutrition and Nigerian women experience long-term discrimination in the allocation and control of productive resources. Nigeria has policies and a governance architecture in place to advance nutrition, but these commitments lack recognition of how gender equity and nutrition are interwoven. Objective: To address this gap, this study sought to identify and analyze the influence of gender dynamics and gender norms on nutrition and health-related practices in Nigeria. Methods: This study used a combination of qualitative participatory activities and participant observation and questions to elicit information about the root causes of maternal, infant, and young child nutrition (MIYCN) and health concerns and typical nutrition and health practices in communities located across each of Nigeria’s 6 geopolitical zones. This analysis was informed by social norms theory and sought evidence of gender norms, as well as related social sanctions and norms exceptions. Results: Analysis of discussions with 503 participating men and women identified 3 overarching gender meta-norms that dictate women’s mobility, gendered delineation of household tasks, and gendered decision-making and, therefore, in turn influence women’s and men’s engagement in recommended MIYCN behaviors such as involvement in production and purchasing of nutritious foods and seeking healthcare and nutrition counseling. Participants also described strong traditional gender ideologies and sanctions that uphold these restrictive norms. Encouragingly, participants described some exceptions to norms, which could indicate changing gender norms. Conclusions: Nigeria currently has one of the highest rates of acute food and nutrition insecurity in Africa and contends with persistent gender inequalities. Interventions are needed that more explicitly tackle the links between gender inequality and nutrition. This analysis revealed gender meta-norms, and related sanctions and exceptions that affect multiple MIYCN behaviors and offer potential entry points for community engagement, programming, and policy around these issues.

Summary: The highly repetitive and transcriptionally active ribosomal DNA (rDNA) genes are exceedingly susceptible to genotoxic stress. Induction of DNA double-strand breaks (DSBs) in rDNA repeats is associated with ataxia-telangiectasia-mutated (ATM)-dependent rDNA silencing and nucleolar reorganization where rDNA is segregated into nucleolar caps. However, the regulatory events underlying this response remain elusive. Here, we identify protein UFMylation as essential for rDNA-damage response in human cells. We further show the only ubiquitin-fold modifier 1 (UFM1)-E3 ligase UFL1 and its binding partner DDRGK1 localize to nucleolar caps upon rDNA damage and that UFL1 loss impairs ATM activation and rDNA transcriptional silencing, leading to reduced rDNA segregation. Moreover, analysis of nuclear and nucleolar UFMylation targets in response to DSB induction further identifies key DNA-repair factors including ATM, in addition to chromatin and actin network regulators. Taken together, our data provide evidence of an essential role for UFMylation in orchestrating rDNA DSB repair.

Schwannomas are tumors that commonly affect the nerve sheath, typically involving peripheral and cranial nerves. These tumors are rarely found within the pelvis and retroperitoneum. To date, there have been no documented cases of concurrent chromophobe renal cell carcinoma and pelvic schwannoma. We present the case of a 57-year-old female with a right renal mass significant for chromophobe renal cell carcinoma and a left pelvic mass found to be a schwannoma. This case highlights the importance of adding schwannoma to the differential when considering a pelvic mass in the setting of renal cell carcinoma.

Menstruation is a worldwide biological phenomenon that can have differing impacts based on what women were taught by their family members and friends. The purpose of this investigation was to understand menstruation experiences and communication, from menarche through menopause, among a sample of cross-generational women living in Florence, Italy. In-depth interviews (n=28) were conducted in English in May and June 2022 to investigate different aspects affecting menstruation throughout a woman’s lifetime. Most participants reported having received limited preparation for menarche, menstruation, and menopause. Education typically came from the participants’ mothers rather than school, which can be attributed to the culture and religion ingrained within Italian society. and menstrual health is still seen as a taboo by older generations. However, discussing these topics with friends and family is becoming more common among younger generations. Results indicated Italian women’s experiences surrounding menarche, menstruation, and menopause, including preparation, education, and openness and discussion. Findings revealed the changing perceptions and generational differences within Italian culture regarding women’s menstruation. This will allow educators, healthcare providers, and families to better understand what education is currently being provided and where more is needed.

Sugar kelp (Saccharina latissma) has many nutritional benefits and has been identified as a rich source of fibre, vitamins, and antioxidants. However, it is not regularly consumed in the Western world, and the sensory perception of foods containing sugar kelp must be investigated to increase acceptance in North America. This study evaluated consumers’ (n = 99) sensory perception of couscous with increasing amounts of sugar kelp (0% (control), 4%, 6%, 8%, and 10% wt/wt). Furthermore, consumers’ purchase intent, liking, and emotional response to couscous with added sugar kelp was evaluated with and without nutritional information. Sugar kelp at 6% incorporation did not impact the consumers’ liking scores (“Like Slightly” on the hedonic scale), but at 8% the consumers’ liking significantly decreased (“Neither Like nor Dislike”). The 8% and 10% levels of sugar kelp addition led to astringency, bitter, hard, brackish, fishy, and chewy attributes being perceived by the consumers. The consumers identified they preferred samples that had soft, savoury, salty, and bland flavours and disliked samples that were brackish and gritty. The nutritional information did not increase overall liking scores, purchase intent, or emotional response. However, the inclusion of sugar kelp in the couscous did lead to an increased selection of positive emotions like happy, joyful, pleasant, and enthusiastic. Overall, the consumers were interested in foods containing seaweed and believed they were nutritious. The results indicated that sugar kelp could be added to couscous up to 6% wt/wt without impacting overall liking.

Objectives: The aims of the study were to (1) describe types of pain in cancer patients, (2) examine the predictors and consequences of pain, (3) investigate the association between type of pain and survival, and (4) examine potential biological mediators of pain and survival. Methods: This was a secondary analysis of baseline data from patients diagnosed with cancer. Patients answered questionnaires that assessed sociodemographic characteristics, pain, depression, sleep, and fatigue. Blood was collected and cytokine assays were performed. Analysis of variance, Kaplan–Meier, and Cox regression survival analyses were used to test the aims. Results: Of the 779 patients diagnosed with cancer, the mean age was 63.5 years, 57.8% male, and 90.6% White. Of those who reported pain (total 70.3%), 46.5% stated their pain was cancer-related while 53.5% stated their pain was non-cancer-related. While both cancer and non-cancer-related pain was associated with depressive symptoms, fatigue, and sleep duration, those with cancer-related pain had significantly higher rates of depressive symptoms (F(1,516) = 21.217, p < 0.001) and fatigue (F(1,516) = 30.973, p < 0.001) but not poorer sleep (F(1,497) = 0.597, p = 0.440). After adjusting for sociodemographic, disease-related characteristics, depression, sleep duration, and morphine milligram equivalent, patient reports of cancer-related pain were significantly associated with poorer survival (HR = 0.646, 95% CI = 0.459–0.910, p = 0.012) compared to those with non-cancer-related pain, which was not associated with survival (HR = 1.022, 95% CI = 0.737–1.418, p = 0.896). Cytokines did not significantly mediate the link between pain and survival. Conclusion: While nearly half of the pain reported was cancer-related, both types of pain resulted in greater symptom burden, but only cancer-related pain was associated with survival.

Plant-based alternatives are a growing market segment, but they have been found to be associated with different flavours, textures, and aftertastes than conventional dairy products. The aim of this study was to evaluate consumer perception of plant-based beverages’ (PBBs) and plant-based cheeses’ (PBCs) aftertaste. Two sensory trials were conducted: one investigating PBBs (n = 104) and the other PBCs (n = 109). In both trials, five different samples (PBBs or PBCs) were evaluated using nine-point hedonic scales, intensity scales and a word association task. The participants were asked to provide the first four words or phrases that described the aftertaste of each sample during the word association task. The results found that as the aftertaste intensity increased, the participant's overall liking of the food product decreased. Consumers preferred plant-based alternatives to have an aftertaste that mimics conventional dairy products. Consumers also identified mouthcoating and textural properties when describing the aftertaste of PBBs and PBCs. Lastly, a strong and lingering aftertaste was disliked by the consumers, while PBBs and PBCs with a quick and mild aftertaste were preferred.

The article explores Kentucky Nurse Practitioners' attitudes and knowledge regarding opioid overdose and naloxone distribution. Topics include naloxone's role in overdose prevention, Nurse Practitioners concerns about prescribing, and recommendations for clearer prescribing protocols to enhance access and mitigate opioid-related fatalities.

The influence of sex and reciprocal cross type were evaluated in Brahman-sired (B × A) and Angussired (A × B) F1 cattle following modified-live viral vaccination regarding virus neutralization titers (VNT) and cell-mediated immune (CMI) responses following in vitro exposure to Bovine Viral Diarrhea Virus (BVDV) Type 1 (BVDV1) and Type 2 (BVDV2) genotypes. VNT against BVDV were based on virus neutralization assay, and CMI responses were measured using the PrimeFlow mRNA assay for determination of the frequency of BVDV and interferon-gamma (IFN-γ) positive cells. Mixed model procedures utilized individual calf ID as a random effect with fixed effects of F1 cross type, calf sex, evaluation date, and potential 2-way interactions; models for frequency of BVDV and IFN-γ positive cells, stimulation conditions (BVDV1, BVDV2, mitogen, none) and potential two-way and three-way interactions of fixed effects. Relationships of immune responses with calf birth weight and weaning weight and steer carcass traits were also investigated. This study found several CMI traits differed due to the type of cross and calf sex; however, no differences in VNT were attributed to these effects. Cells from B × A animals consistently ranked approximately 20% greater for BVDV positive cells (BVDV+) than those from A × B animals pre-MLV vaccination; however, post-MLV vaccination, cells from A × B animals ranked 20% greater (P < 0.05) for CD2+, CD4+, and CD8+ cells. Post-MLV steers consistently had 30 to 35% greater (P < 0.05) frequencies of BVDV+ cells following viral exposure; steers had greater frequencies (P < 0.05) of CD4+ and CD335+ cells expressing IFN-γ and ranked greater for CD2+ and CD8+ cells when compared with heifers in both crosses. Only vaccination timing affected BVDV VNT. No significant correlations involving VNT and CMI responses were observed among A × B animals when stimulated with BVDV1, but among B × A animals, positive correlations were observed with IFN-γ in CD4+ (r = 0.406, P = 0.049) and CD335+ (r = 0.472, P = 0.020). When stimulated with BVDV2, positive correlations of 0.33 to 0.39 (P < 0.05) were observed between BVDV and IFN-γ frequency within cell type; these were not significant when stimulated with BVDV1, except for CD335+ cells (r = 0.41, P = 0.003). No correlations for VNT and CMI responses were observed when stimulated with BVDV2. No major correlations between immune responses and weight or carcass traits were observed, and immune response category for BVDV or IFN-γ frequency did not influence birth weight or weaning weight. Differences in CMI responses involving reciprocal cross types and sex observed in this project may relate to widely reported reciprocal cross differences in birth weight in Bos indicus - Bos taurus crossbred cattle and warrant additional study. [ABSTRACT FROM AUTHOR]

Objective To determine current UK medical students’ career intentions after graduation and on completing the Foundation Programme (FP), and to ascertain the motivations behind these intentions.Design Cross-sectional, mixed-methods survey of UK medical students, using a non-random sampling method.Setting All 44 UK medical schools recognised by the General Medical Council.Participants All UK medical students were eligible to participate. The study sample consisted of 10 486 participants, approximately 25.50% of the medical student population.Outcome measures Career intentions of medical students postgraduation and post-FP, motivations behind these career intentions, characterising the medical student population and correlating demographic factors and propensity to leave the National Health Service (NHS).Results The majority of participating students (8806/10 486, 83.98%) planned to complete both years of the FP after graduation, with under half of these students (4294/8806, 48.76%) intending to pursue specialty training thereafter. A subanalysis of career intentions after the FP by year of study revealed a significant decrease in students’ intentions to enter specialty training as they advanced through medical school. Approximately a third of surveyed students (3392/10 486, 32.35%) intended to emigrate to practise medicine, with 42.57% (n=1444) of those students not planning to return. In total, 2.89% of students intended to leave medicine altogether (n=303). Remuneration, work-life balance and working conditions were identified as important factors in decision-making regarding emigration and leaving the profession. Subgroup analyses based on gender, type of schooling, fee type and educational background were performed. Only 17.26% of surveyed students were satisfied or very satisfied with the overall prospect of working in the NHS.Conclusions The Ascertaining the career Intentions of UK Medical Students study highlights UK students’ views and career intentions, revealing a concerning proportion of those surveyed considering alternative careers or emigration. Addressing factors such as remuneration, work-life balance and working conditions may increase retention of doctors and improve workforce planning efforts.

Background: Children with severe neurologic impairment (SNI) regularly require major surgery to manage their underlying conditions. Anecdotal evidence suggests that children with SNI experience unexpected and persistent postoperative functional changes long after the postoperative recovery period; however, evidence from the perspective of caregivers is limited. The purpose of the study was to explore the functional postoperative recovery process for children with SNI. Methods: Eligible participants were English-speaking caregivers of children with SNI between 6 months and 17 years who were nonverbal, Gross Motor Function Classification Scale level IV/V, and who had surgery/procedure requiring general anesthetic at a tertiary children’s hospital between 2012 and 2022. Demographic and basic health information were collected via surveys and corroborated by a review of the child’s electronic health record. Semi-structured interviews were conducted and a thematic content analysis was used to formulate results. Results: Data from 12 primary caregiver interviews revealed four main themes: (1) functional changes and complications in the child; (2) feeling unprepared; (3) perioperative support; and (4) changes to caregiver roles. Conclusions: Postoperative functional decline in children with SNI was prevalent in our sample. Providing pre-operative information to families to describe this phenomenon should be a regular part of family-informed care.

ABSTRACT The intracellular parasite Toxoplasma gondii induces host AKT activation to prevent autophagy-mediated clearance; however, the molecular underpinnings are not fully understood. Autophagy can be negatively regulated through AKT-sensitive phosphorylation and nuclear export of the transcription factor Forkhead box O3a (FOXO3a). Using a combination of pharmacological and genetic approaches, herein we investigated whether T. gondii hinders host autophagy through AKT-dependent inactivation of FOXO3a. We found that infection by type I and II strains of T. gondii promotes gradual and sustained AKT-dependent phosphorylation of FOXO3a at residues S253 and T32 in human foreskin fibroblasts (HFF) and murine 3T3 fibroblasts. Mechanistically, AKT-sensitive phosphorylation of FOXO3a by T. gondii required live infection and the activity of PI3K but was independent of the plasma membrane receptor EGFR and the kinase PKCα. Phosphorylation of FOXO3a at AKT-sensitive residues was paralleled by its nuclear exclusion in T. gondii-infected HFF. Importantly, the parasite was unable to drive cytoplasmic localization of FOXO3a upon pharmacological blockade of AKT or overexpression of an AKT-insensitive mutant form of FOXO3a. Transcription of a subset of bona fide autophagy-related targets of FOXO3a was reduced during T. gondii infection in an AKT-dependent fashion. However, parasite-directed repression of autophagy-related genes was AKT-resistant in cells deficient in FOXO3a. Consistent with this, T. gondii failed to inhibit the recruitment of acidic organelles and LC3, an autophagy marker, to the parasitophorous vacuole upon chemically or genetically induced nuclear retention of FOXO3a. In all, we provide evidence that T. gondii suppresses FOXO3a-regulated transcriptional programs to prevent autophagy-mediated killing. IMPORTANCE The parasite Toxoplasma gondii is the etiological agent of toxoplasmosis, an opportunistic infection commonly transmitted by ingestion of contaminated food or water. To date, no effective vaccines in humans have been developed and no promising drugs are available to treat chronic infection or prevent congenital infection. T. gondii targets numerous host cell processes to establish a favorable replicative niche. Of note, T. gondii activates the host AKT signaling pathway to prevent autophagy-mediated killing. Herein, we report that T. gondii inhibits FOXO3a, a transcription factor that regulates the expression of autophagy-related genes, through AKT-dependent phosphorylation. The parasite’s ability to block the recruitment of the autophagy machinery to the parasitophorous vacuole is impeded upon pharmacological inhibition of AKT or overexpression of an AKT-insensitive form of FOXO3a. Thus, our study provides greater granularity in the role of FOXO3a during infection and reinforces the potential of targeting autophagy as a therapeutic strategy against T. gondii.

BackgroundAcute flaccid myelitis (AFM) occurs rarely in children and adolescents when damage to spinal motor neurons rapidly causes flaccid paralysis of limb, trunk, and neck muscles and potentially respiratory failure. When neck muscles are weakened or paralyzed, a child loses head control, severely compromising engagement with their environment. Compensation for lack of head control is achieved with external support devices attached to a wheelchair, but there is no indication in the AFM literature of therapeutic efforts to restore head control. In this case series, we explore the possibility of the recovery of head control when children with AFM received activity-based restorative therapies (ABRTs) guided by principles targeting motor control.Case descriptionThree children, two male and one female, aged 6, 9, and 7, with a history of AFM-onset at 5, 7, and 4 years respectively, enrolled in an activity-based restorative therapies outpatient program targeting activation of the neuromuscular system below the lesion. Each of them lacked head control, was either ventilator-dependent or had a tracheostomy, and was a power wheelchair user via hand/foot control.MethodsActivity-based restorative therapies were provided 5 days/week: 1.5 h of activity-based locomotor training and 1.5 h of activity-based neuromuscular electrical stimulation.ResultsAn approach to addressing head/neck control developed iteratively across disciplines, from complete compensation with passive external head support to emerging head control during diverse tasks, e.g., sitting, reaching, driving a power chair, sit-to-stand, standing, stepping on a treadmill, and walking. Key principles identified and employed were (a) passive facilitation, (b) external head support, (c) posterior head support, (d) graded manual facilitation, and (e) independent head control.DiscussionThe recovery of head control in children with paralysis due to AFM may be accelerated when executing a step-wise progression to effectively target and challenge head control in parallel with activity-based restorative therapies. In treating three children with a chronic lack of head control, a therapeutic strategy was iteratively developed guided by scientific principles, e.g., segmental assessment of control, to promote recovery of head control. While this strategy is encouraging, gaps in sensitive and responsive measurement instruments and treatment technologies persist in guiding assistance, challenging, and promoting independent head control.

BackgroundSpinal cord injury (SCI) in infancy halts typical development secondary to paralysis/paresis and the limited ability to engage with the environment. Traditional therapies further restrict a child via bracing, equipment, and medications. In contrast, activity-based restorative therapies (ABRT) promote activation of the neuromuscular system below the level of injury and affords a more typical sensorimotor experience.Case DescriptionA premature male infant exhibiting hypotonia, poor head control, and extremity weakness was diagnosed at age 5 months with a remote incomplete upper cervical SCI based on magnetic resonance imaging (MRI), presumed to have occurred perinatally. From 4 to 15 months of age, he received physical, occupational and speech therapies. Enrolled in an ABRT program at 15 months, he was unable to sit, pull-to-stand, stand, or walk and had upper extremity impairments. Results of the Bayley-III Scales of Infant and Toddler Development revealed gross and fine motor scores consistent with a 4-month-old.MethodsActivity-based restorative therapies was provided 5 day/week: 1.5 h of activity-based locomotor training and 1 h of activity-based occupational therapy.ResultsActivity-based restorative therapies are reported for 177 sessions and are on-going. Improvements are noted in trunk control, standing, walking, grasp, in-hand manipulation, and associated kinematics. Bayley-III fine motor score improved to that of a 16-month-old and gross motor score to that of a 7-month-old.DiscussionWhile the two treatment periods (i.e., 4–15 months old and 15–24 months) were each ∼9 months, the child’s accelerated progress toward typical development during the latter, ABRT period is noteworthy. In comparison to the period of traditional therapies in which paralysis was compounded by a restrictive environment and compensation, ABRT provided a potentially rich sensorimotor experience with an emphasis on active weight-bearing and proper kinematics to activate the neuromuscular system below the lesion in an age-appropriate, task-specific context of activities. Improved physical capacity enabled exploration more typically associated with development at this age expanding the positive impact to other developmental domains.

Consumers are interested in plant-based alternatives (PBAs) to dairy and meat products, and as such, the food industry is responding by developing a variety of different plant-based food items. For these products to be successful, their textural properties must be acceptable to consumers. These textural properties need to be thoroughly investigated using different sensory methodologies to ensure consumer satisfaction. This review paper aims to summarize the various textural properties of PBAs, as well as to discuss the sensory methodologies that can be used in future studies of PBAs. PBAs to meat have been formulated using a variety of production technologies, but these products still have textural properties that differ from animal-based products. Most dairy and meat alternatives attempt to mimic their conventional counterparts, yet sensory trials rarely compare the PBAs to their meat or dairy counterparts. While most studies rely on consumers to investigate the acceptability of their products’ textural properties, future studies should include dynamic sensory methodologies, and attribute diagnostics questions to help product developers characterize the key sensory properties of their products. Studies should also indicate whether the product is meant to mimic a conventional product and should define the target consumer segment (ex. flexitarian, vegan) for the product. The importance of textural properties to PBAs is repeatedly mentioned in the literature and thus should be thoroughly investigated using robust sensory methodologies.

Chemical irritants, like piperine, have the potential to increase human perception of tastes and odours, including saltiness. This cross-modal interaction could help the food industry develop new salt-reduced food products that maintain their salty taste. The objective of this study was: firstly, to determine the detection threshold of piperine (n = 72), secondly to evaluate piperine’s influence on saltiness perception in model solutions (n = 78), and lastly to identify piperine’s effect on sensory perception of low sodium soup using temporal check-all-that-apply (TCATA; n = 75). The group mean of the individual threshold was 0.55 ± 0.15 ppm. Piperine increased the saltiness perception of the model solutions, but it also increased the bitterness and decreased the sweetness of the solutions. The piperine significantly increased the saltiness intensity of the soups (evaluated using a generalized labelled magnitude), but during the TCATA task, the salty attribute was selected less for the soup with piperine than the control (based on the average proportion of selection). The TCATA indicated that the peppery attribute dominated the participants’ perception of the soup with piperine. More studies are needed to assess piperine’s cross-modal interactions.

The prevalence of plant-based alternatives (PBAs) to meat in the marketplace has been increasing in recent years due to consumer demand. One of these plant-based products has aimed to mimic chicken products, specifically chicken nuggets. However, few sensory studies have been conducted on these products. The objective of this study is to evaluate the sensory properties, acceptability, and consumer perception of these PBAs. Participants (n = 105) were asked to evaluate five PBAs and a control (chicken nugget) using hedonic scales and a check-all-that-apply question. They also answered an open-ended comment question about PBAs. The participants separated the control from the PBAs in terms of their hedonic scores and sensory properties. They separated the PBAs based on their textural properties and if they had off-flavors. Participants disliked PBAs that were associated with an aftertaste, as well as beany, fibrous, and chewy attributes. The participants believed the PBAs currently on the market did not successfully mimic a chicken nugget and that improvement is needed, but they did believe PBAs are environmentally friendly.

Grimontia hollisae, an uncommon cause of sepsis, was identified in a 9-month-old infant in Africa without confirmed seafood consumption. Prompt diagnosis through blood culture and targeted antibiotic therapy ensured recovery, emphasizing the need for increased awareness, enhanced diagnostic tools, and active monitoring of emerging pathogens in tropical and resource-limited regions. We present a case report involving a 9-month-old infant who exhibited symptoms of acute gastroenteritis. The blood culture revealed G. hollisae . We treated the infant on empirical first-line antibiotics of IV ceftriaxone, IV gentamicin, zinc tablets, and syrup paracetamol for 5 days after which the child was discharged on oral metronidazole following resolution of symptoms. This case highlights the importance of G. hollisae in causing sepsis in infants in tropical settings. It also emphasizes the need for blood culture investigation and administering the appropriate antibiotics in the diagnosis of children presenting with suspected sepsis., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Introduction: Presbyopia, difficulty in seeing close-ups, affects a billion people globally. Mobile financial services (MFS) have been mandated since January 2021 for Bangladesh government social safety net payments, including old age allowance (OAA) and widow allowance (WA). We report the protocol for the Transforming Households with Refraction and Innovative Financial Technology randomised trial assessing the impact on the use of online banking of providing presbyopic safety net beneficiaries with reading glasses, and brief smartphone and mobile banking app training., Methods and Analyses: Eligible participants (n=484) are OAA (men aged 65-70 years; women aged 62-70) or WA recipients (women aged 48-60) with presbyopia as their only vision problem, passing a smartphone-based test of numeracy, cognition and dexterity, and not currently owning a smartphone or independently using MFS. All participants receive smartphones loaded with a mobile banking app and a transaction-tracking app and are randomised 1:1 to receive immediate free near-vision glasses and half-day training for smartphone and banking app use (intervention), or glasses and training 12 months later (control). The primary outcome is the mean quarterly number of mobile bank transactions over the 12-month follow-up period, comparing study groups, with and without adjustment. Secondary outcomes include food security, healthcare access and social connectedness., Ethics and Dissemination: The protocol was approved by ethics committees at Queen's University Belfast (reference #MHLS22&#95;69) and BRAC James P Grant School of Public Health (reference #IRB-21 August'22-028). The trial is conducted in accordance with the Declaration of Helsinki and national regulations in Bangladesh, and results will be published in open-access, peer-reviewed journals., Trial Registration Number: NCT05510687; ClinicalTrials.gov., Competing Interests: Competing interests: GM discloses a potential conflict of interest arising from his dual roles: Director of Research at Clearly Initiatives, a co-funding entity for the trial, and contributor to the study's design and conceptualisation. In these capacities, GM actively participated in shaping the research framework, defining objectives and contributing to the methodology of the study. AS discloses a potential conflict of interest as an advisor of the MOMODa Foundation, the implementation agency of the THRIFT trial in Bangladesh and a contributor to the study's design and conceptualisation. SAS, IBA, PP, LL, SR, NgC, PS, LNS, HMMR, RCK, VFC, MB, SP, AA, AN, MS, ALM, EH, SA, EG, MC, AR and NC declare having no conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ Group.)

Objectives: The prior event rate ratio (PERR) is a recently developed approach for controlling confounding by measured and unmeasured covariates in real-world evidence research and observational studies. Despite its rising popularity in studies of safety and effectiveness of biopharmaceutical products, there is no guidance on how to empirically evaluate its model assumptions. We propose two methods to evaluate two of the assumptions required by the PERR, specifically, the assumptions that occurrence of outcome events does not alter the likelihood of receiving treatment, and that earlier event rate does not affect later event rate., Study Design and Setting: We propose using self-controlled case series (SCCS) and dynamic random intercept modeling (DRIM), respectively, to evaluate the two aforementioned assumptions. A nonmathematical introduction of the methods and their application to evaluate the assumptions are provided. We illustrate the evaluation with secondary analysis of deidentified data on pneumococcal vaccination and clinical pneumonia in The Gambia, West Africa., Results: SCCS analysis of data on 12,901 vaccinated Gambian infants did not reject the assumption of clinical pneumonia episodes had no influence on the likelihood of pneumococcal vaccination. DRIM analysis of 14,325 infants with a total of 1719 episodes of clinical pneumonia did not reject the assumption of earlier episodes of clinical pneumonia had no influence on later incidence of the disease., Conclusion: The SCCS and DRIM methods can facilitate appropriate use of the PERR approach to control confounding., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Enterobacter cloacae is the leading cause of morbidity and mortality in the genus Enterobacter . It mostly causes nosocomial infections, especially in children, the elderly and those with underlying diseases. However, cases of community-acquired bacteraemia caused by E. cloacae have been reported. The increasing inclination of E. cloacae to cause multidrug-resistant infections has made it particularly challenging to treat. A 25-month-old male child presented to a rural hospital in The Gambia with a one-week history of persistent high-grade fever, dyspnoea, and anorexia. Two days before presentation, he began to have generalized tonic-clonic seizures. On examination, he was found to be febrile, dyspnoeic, pale, and tachycardic. He had a modified Glasgow Coma Scale score of 9/15. Investigations revealed an elevated C-reactive protein, low haemoglobin, and elevated white blood cell count. Cerebrospinal fluid culture did not yield any growth. E. cloacae was isolated from a blood culture taken on the day of admission. The pathogen was resistant to all available antibiotics. He was transfused with whole blood and initially treated empirically with amoxicillin-clavulanic acid and gentamicin. The former was changed to cefuroxime because the child had not improved. The child died nine days after admission. Although E. cloacae is primarily known for causing nosocomial infections, fatal community-acquired infections also occur. This case report demonstrates the difficulty in treating multidrug-resistant E. cloacae in a low-resource setting and its propensity to cause fatal infections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Key Clinical Message: Ochrobactrum anthropi ( O . anthropi ), a rare opportunistic pathogen, caused sepsis in a malnourished 15-month-old African child. Early detection and appropriate antibiotics led to full recovery, highlighting the importance of robust surveillance for emerging pathogens in vulnerable populations., Abstract: While rarely causing infections, O . anthropi , a non-fermenting, obligately aerobic, flagellated gram-negative bacillus, demonstrates oxidase positivity and indole negativity. Traditionally, Ochrobactrum spp is considered a low threat due to its environmental abundance and mild virulence. It is, however, a multidrug-resistant bacteria known for causing opportunistic infections in humans. O . anthropi is typically associated with catheter-related bloodstream infections. The first documented case was in 1998; most cases have been reported in developed countries. We present a case of O . anthropi sepsis in a malnourished child in sub-Saharan Africa. We report a case involving a 15-month-old African female who presented with symptoms and signs of protein-energy malnutrition and sepsis. The blood culture revealed O . anthropi . We treated the child with the empirical first-line antibiotics per the national guidelines, intravenous ampicillin and gentamicin for a week, and the child fully recovered. This report describes a rare case of O . anthropi sepsis with malnutrition in an African female child. O . anthropi is an emerging pathogen causing opportunistic infections in both immunocompetent and immunocompromised patients. We report that early bacterial detection, appropriate antibiotic susceptibility and antimicrobial management based on local antibiogram data may be essential for excellent patient outcomes. Additionally, we recommend more robust surveillance to detect such rare emerging pathogens., Competing Interests: The authors declare that they have no competing interests in this section., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Apathy is a common and disabling complication of Parkinson's disease characterized by reduced goal-directed behaviour. Several studies have reported dysfunction within prefrontal cortical regions and projections from brainstem nuclei whose neuromodulators include dopamine, serotonin and noradrenaline. Work in animal and human neuroscience have confirmed contributions of these neuromodulators on aspects of motivated decision-making. Specifically, these neuromodulators have overlapping contributions to encoding the value of decisions, and influence whether to explore alternative courses of action or persist in an existing strategy to achieve a rewarding goal. Building upon this work, we hypothesized that apathy in Parkinson's disease should be associated with an impairment in value-based learning. Using a four-armed restless bandit reinforcement learning task, we studied decision-making in 75 volunteers; 53 patients with Parkinson's disease, with and without clinical apathy, and 22 age-matched healthy control subjects. Patients with apathy exhibited impaired ability to choose the highest value bandit. Task performance predicted an individual patient's apathy severity measured using the Lille Apathy Rating Scale (R = -0.46, P < 0.001). Computational modelling of the patient's choices confirmed the apathy group made decisions that were indifferent to the learnt value of the options, consistent with previous reports of reward insensitivity. Further analysis demonstrated a shift away from exploiting the highest value option and a reduction in perseveration, which also correlated with apathy scores (R = -0.5, P < 0.001). We went on to acquire functional MRI in 59 volunteers; a group of 19 patients with and 20 without apathy and 20 age-matched controls performing the Restless Bandit Task. Analysis of the functional MRI signal at the point of reward feedback confirmed diminished signal within ventromedial prefrontal cortex in Parkinson's disease, which was more marked in apathy, but not predictive of their individual apathy severity. Using a model-based categorization of choice type, decisions to explore lower value bandits in the apathy group activated prefrontal cortex to a similar degree to the age-matched controls. In contrast, Parkinson's patients without apathy demonstrated significantly increased activation across a distributed thalamo-cortical network. Enhanced activity in the thalamus predicted individual apathy severity across both patient groups and exhibited functional connectivity with dorsal anterior cingulate cortex and anterior insula. Given that task performance in patients without apathy was no different to the age-matched control subjects, we interpret the recruitment of this network as a possible compensatory mechanism, which compensates against symptomatic manifestation of apathy in Parkinson's disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Without complete data on under-5 mortality, tracking progress towards achieving Sustainable Development Goal 3.2 will be challenging. Such data are also needed to ensure proper planning and prioritisation of scarce resources in low-income and middle-income countries. However, most low-income and middle-income countries have weak Civil Registration and Vital Statistics (CRVS) systems, leaving a critical gap in understanding under-5 mortality dynamics. This paper outlines a community-based approach to enhance under-5 mortality surveillance in low-income countries, using The Gambia as a case study. The methodology involves Health and Demographic Surveillance Systems (HDSSs) in Basse and Fuladu West, employing unique identification numbers, periodical household visits and collaboration with communities, village reporters and project field workers to ensure comprehensive data collection. Verbal autopsies (VAs) are conducted by trained field workers, and causes of death are determined using the physician-certified VA method. Between 1 September 2019 and 1 September 2023, 1333 deaths were detected, for which causes of death were determined for 97.1% (1294 of 1333). The most common causes of death detected were acute respiratory infections including pneumonia, sepsis, diarrhoeal diseases and birth asphyxia. Challenges include the cost of maintaining the HDSSs, poor road infrastructure, Electronic Data Capture transition challenges, and the need for national integration of HDSS data into the CRVS system. The success of this model highlights its potential for scalable and adaptable under-5 mortality surveillance in resource-limited settings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Lung cancer is a major cause of death in Western countries, but survival had never been studied in Northern Ireland (NI) on a population basis prior to this study., Aims: The primary aims were to describe the survival of patients with primary lung cancer, evaluate the effect of treatment, identify patient characteristics influencing survival and treatment and describe current trends in survival., Methods: A population-based study identified all incident cases of primary lung cancer in NI during 1991-2 and followed them for 21 months. Their clinical notes were traced and relevant details abstracted. Survival status was monitored via the Registrar General's Office, and ascertainment is thought to be near-complete. Appropriate statistical methods were used to analyse the survival data., Results: Some 855 incident cases were studied. Their 1-year survival was 24.5% with a median survival time of 4.7 months. Surgical patients had the best 1-year survival, 76.8%; however, adjustment suggested that about half of the benefit could be attributed to case-mix factors. Factors influencing treatment allocation were also identified, and a screening test showed the discordance between 'model' and 'medic': 210 patients were misclassified. Finally, the current trend in 1-year survival observed in the Republic of Ireland was best in the British Isles., Conclusions: Overall, survival remains poor. The better survival of surgical patients is due, in part, to their superior case-mix profiles. Survival with other therapies is less good suggesting that the criteria for treatment might be relaxed with advantage using a treatment model to aid decision-making., (© 2023. The Author(s).)

Background: Stenotrophomonas maltophilia is a gram-negative bacteria known for causing opportunistic and nosocomial infections in humans. S. maltophilia is an emerging pathogen of concern due to it's increasing prevalence, diverse disease spectrum, intrinsic multi-drug resistance and high mortality rates in immunocompromised individuals. S. maltophilia is a rare cause of neonatal sepsis associated with significant morbidity and mortality. The bacterium's multi-drug resistance poses a considerable challenge for treatment, with various mechanisms contributing to its resistance., Case Presentation: We report a case involving a 40-h-old male African neonate who exhibited symptoms of neonatal sepsis. The blood culture revealed Stenotrophomonas maltophilia, which was sensitive to ciprofloxacin and gentamicin but resistant to other antibiotics. Lumbar puncture for CSF could not be done because the father declined. We treated the newborn with the empirical first-line antibiotics as per the national guideline intravenous ampicillin and gentamicin for six days, and the child recovered fully with a repeated negative blood culture., Conclusions: This report describes a neonatal sepsis case caused by S. maltophilia, a multi-drug resistant bacteria and a rare cause of neonatal sepsis. We report that early detection of the bacterial and antimicrobial management based on local antibiogram data may be essential for successful patient's management., (© 2024. The Author(s).)

Objective: The measures implemented to control the spread of Coronavirus disease 2019 (COVID-19) could affect children's mental and vision health. Youth particularly from minority and socioeconomically disadvantaged backgrounds were more likely to be impacted by these measures. This study aimed to examine the mental health of children with vision impairment and associated factors in North-western China during the COVID-19 pandemic., Methods: A cross-sectional study was conducted among 2,036 secondary school children living in Ningxia Hui Autonomous Region. Participants completed a survey on sociodemographic and lifestyle information and answered the Chinese version of the 21-item Depression Anxiety Stress Scales (DASS-21) questionnaire. Presenting visual acuity was measured by a trained enumerator. Multivariate logistic regression analysis was used to identify potential risk factors for mental health problems., Results: Responses from 1,992 (97.8%) children were included in the analysis after excluding those with incomplete mental health outcome data. The prevalence of depression, anxiety and stress symptoms within the dataset were 28.9, 46.4, and 22.3%, respectively. The distribution of children with different stress levels differed significantly between those with and without vision impairment ( p  = 0.03). Multivariable logistic regression analyses revealed that depression symptoms decreased with higher parental education (OR, 0.76, 95% confidence intervals (CI):0.63-0.96), longer sleep duration (OR, 0.90, 95% CI: 0.81-0.97) and longer study time (OR, 0.82, 95% CI: 0.74-0.91), whereas they increased with higher recreational screen time (OR, 1.19, 95% CI: 1.08-1.32). Anxiety symptoms decreased with higher parental education (OR, 0.80, 95% CI: 0.66-0.96) and increased with higher recreational screen time (OR, 1.15, 95% CI: 1.04-1.27) and being a left-behind child (OR, 1.26, 95% CI: 1.04-1.54). In addition, stress symptoms decreased with longer sleep duration (OR, 0.92, 95%CI: 0.85-0.99) and increased with higher number of siblings (OR, 1.10, 95% CI: 1.01-1.19), higher recreational screen time (OR, 1.15, 95% CI: 1.04-1.28) and older age (OR,1.12, 95% CI: 1.004-1.24)., Conclusion: A considerable proportion of our sample experienced mental health problems during the pandemic. Healthcare planners in China should consider interventions such as reducing recreational screen time, ensuring sufficient sleep, and timely detection of mental health symptoms among socioeconomically disadvantaged groups., Competing Interests: MS has received research support from Stanford’s Maternal Child Health Research Institute and Stanford’s Department of Psychiatry and Behavioral Sciences, National Institute of Mental Health, National Institute of Aging, Patient Centered Outcomes Research Institute, Johnson and Johnson, and the Brain and Behavior Research Foundation. She was on the advisory board for Sunovion and Skyland Trail, was a consultant for Johnson and Johnson, Alkermes, Neumora, AbbVie, Karuna Therapeutics, Inc., and Boehringer-Ingelheim. She received honoraria from the American Academy of Child and Adolescent Psychiatry, and royalties from American Psychiatric Association Publishing and Thrive Global. GM is the research director of Clearly Initiatives and contributed to the design of this study. BX received a Ph.D. scholarship from Clearly Initiatives. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Chan, Wang, Zhang, Virgili, Whitestone, Xiao, Singh, She, Mackenzie, Boswell, Mavi, Rozelle and Congdon.)

Gene therapy holds great promise for treating prostate cancer unresponsive to conventional therapies. However, the lack of delivery systems that can transport therapeutic DNA and drugs while targeting tumors without harming healthy tissues presents a significant challenge. This study aimed to explore the potential of novel hybrid lipid nanoparticles, composed of biocompatible zein and conjugated to the cancer-targeting ligand transferrin. These nanoparticles were designed to entrap the anti-cancer drug docetaxel and carry plasmid DNA, with the objective of improving the delivery of therapeutic payloads to prostate cancer cells, thereby enhancing their anti-proliferative efficacy and gene expression levels. These transferrin-bearing, zein-based hybrid lipid nanoparticles efficiently entrapped docetaxel, leading to increased uptake by PC-3 and LNCaP cancer cells and significantly enhancing anti-proliferative efficacy at docetaxel concentrations exceeding 1 µg/mL. Furthermore, they demonstrated proficient DNA condensation, exceeding 80% at polymer-DNA weight ratios of 1500:1 and 2000:1. This resulted in increased gene expression across all tested cell lines, with the highest transfection levels up to 11-fold higher than those observed with controls, in LNCaP cells. These novel transferrin-bearing, zein-based hybrid lipid nanoparticles therefore exhibit promising potential as drug and gene delivery systems for prostate cancer therapy.