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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

We performed steered molecular dynamics (SMD) and umbrella sampling simulations of Cl− ion migration through the transmembrane domain of a prototypical E. coli CLC Cl−/H+ antiporter by employing combined quantum-mechanical (QM) and molecular-mechanical (MM) calculations. The SMD simulations revealed interesting conformational changes of the protein. While no large-amplitude motions of the protein were observed during pore opening, the side chain rotation of the protonated external gating residue Glu148 was found to be critical for full access of the channel entrance by Cl−. Moving the anion into the external binding site (Sext) induced small-amplitude shifting of the protein backbone at the N-terminal end of helix F. As Cl− traveled through the pore, rigid-body swinging motions of helix R separated it from helix D. Helix R returned to its original position once Cl− exited the channel. Population analysis based on polarized wavefunction from QM/MM calculations discovered significant (up to 20%) charge loss for Cl− along the ion translocation pathway inside the pore. The delocalized charge was redistributed onto the pore residues, especially the functional groups containing π bonds (e.g., the Tyr445 side chain), while the charges of the H atoms coordinating Cl− changed almost negligibly. Potentials of mean force computed from umbrella sampling at the QM/MM and MM levels both displayed barriers at the same locations near the pore entrance and exit. However, the QM/MM PMF showed higher barriers (~10 kcal/mol) than the MM PMF (~2 kcal/mol). Binding energy calculations indicated that the interactions between Cl− and certain pore residues were overestimated by the semi-empirical PM3 Hamiltonian and underestimated by the CHARMM36 force fields, both of which were employed in the umbrella sampling simulations. In particular, CHARMM36 underestimated binding interactions for the functional groups containing π bonds, missing the stabilizations of the Cl− ion due to electron delocalization. The results suggested that it is important to explore these quantum effects for accurate descriptions of the Cl− transport.

Abstract Background Immigrants to Germany and their children are at particular risk for tuberculosis (TB). Methods 35 Patients (10 male/25 female aged 2 - 59 years (median 33 years) originating mostly from high incidence countries in Asia (19 [54.3%]) in Africa (14 [40.0%] and East Europe (2 [5.7%]), attended at the Tropical Medicine unit were analysed. Results Primary clinical presentation was most frequently lymphadenitis (13 [37.1%]). other organs involved included bones (7 [20.0%]), central nervous system (5 [14.3%]), urogenital organs (3 [8.6%]), lung (3 [8.6%]), mediastinum, (2 [5.7%]) and abdomen (2 [5.7%]). ESR was abnormal in 21/28 (75.0%), CRP in 20/35 (57.1%), and protein electrophoresis in 22/26 (84.6%) cases. The tuberculin skin test was strongly positive in all 15 cases where the test had been performed. Tuberculosis interferon gamma release assay (TB-IGRA) was positive in all 35 cases (100%). PCR for nucleic acids of Mycobacterium (M.) tuberculosis complex was positive in only 7/20 (35.0%) cases. M. tuberculosis was identified in 32/35 (91.4%), M. bovis in 2 (5.7%) cases. 1 case was diagnosed clinically. All patients were negative for HIV. Typical histopathology was seen in the 29 cases, where biopsies had been taken. Chest-X-ray did not reveal specific pulmonary lesions in the majority of cases (22/35 [62.9%]). Diagnosis of TB was mostly delayed (4 to 299 weeks, [median 8]). The most frequent primary suspicion was a malignancy (17/35 [48.6%]) while TB was initially suspected in 5 cases only. Diagnosis of TB is impeded by its multifaceted presentation especially in immigrants.

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]

Purpose: To identify meaningful educative experiences that contributed to the development of rehabilitation counselors' abilities to provide effective rehabilitation counseling services to lesbian, gay, bisexual, transgender, and queer (LGBTQ) persons living with chronic illness/disabilities (CID). Method: This was a secondary analysis of a larger qualitative data set that examined the educational experiences and practices of 12 certified rehabilitation counselors working with LGBTQ persons. Results: Using a qualitative content analysis methodology, 5 categories were identified: (a) formal didactic education, (b) affirmative supervision and consultation during practica/internship, (c) extracurricular-related training, (d) identification, and (e) family of origin. Conclusion: To help facilitate future counselors' self-perceived abilities to provide effective services to LGBTQ persons living with CID, rehabilitation counselor educators should place more emphasis on LGBTQ-related issues in their curriculum and provide practical (experiential) learning opportunities for their students.

Participants' eye movements were monitored in an experiment that manipulated the frequency of target words (high vs. low) as well as their availability for parafoveal processing during fixations on the pre-target word (valid vs. invalid preview). The influence of the word-frequency by preview validity manipulation on the distributions of first fixation duration was examined by using ex-Gaussian fitting as well as a novel survival analysis technique which provided precise estimates of the timing of the first discernible influence of word frequency on first fixation duration. Using this technique, we found a significant influence of word frequency on fixation duration in normal reading (valid preview) as early as 145 ms from the start of fixation. We also demonstrated an equally rapid non-lexical influence on first fixation duration as a function of initial landing position (location) on target words. The time-course of frequency effects, but not location effects was strongly influenced by preview validity, demonstrating the crucial role of parafoveal processing in enabling direct lexical control of reading fixation times. Implications for models of eye-movement control are discussed. (Contains 4 tables and 8 figures.)

Word properties like imageability and word frequency improve cued recall of verbal paired-associates. We asked whether these enhancements follow simply from prior effects on item-memory, or also strengthen associations between items. Participants studied word pairs varying in imageability or frequency: pairs were "pure" (high-high, low-low) or "mixed" (high-low, low-high) where "high" and "low" refer to imageability or frequency values and are probed with forward (A-?) and backward (?-B) cues. Probabilistic model fits to the data suggested that imageability primarily improved retrieval of associations, but frequency primarily improved recall of target items. All pair types exhibited a high correlation between forward and backward probe accuracy, a measure of holistic learning (Kahana, 2002), which extends the boundary conditions of holistic association-memory and challenges Paivio's (1971) suggestion that holistic learning depends critically on imagery. In sum, item properties can boost association-memory beyond simply boosting target retrievability. (Contains 3 tables and 8 figures.)

Paired associates and serial list memory are typically investigated separately. An "isolation principle" (J. B. Caplan, 2005) was proposed to explain behavior in both paradigms by using a single model, in which serial list and paired associates memory differ only in how isolated pairs of items are from interference from other studied items. In the present study, 2 experiments identify a critical dissociation between the 2 paradigms, challenging this unified account. Specifically, forward and backward probes were highly correlated for pairs and less so for short lists (triples). The authors asked whether the isolation principle could quantitatively accommodate this type of dissociation. A simulation confirmed that a single model incorporating the isolation principle can adequately explain this and other dissociations, supporting the common processes view.

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.