Examining whether and how Black and Asian parents engage in collective racial socialization.

OBJECTIVES: Ethnic-racial socialization, or the process by which parents teach their children about race and racism, is often protective for racially minoritized children. However, these processes typically focus on belonging to one's own racialized group. The present work examines whether and when Black and Asian parents might discuss race and racism as it relates to other racially minoritized groups. METHOD: The sample includes 91 parents (54.9% Black, 45.1% Asian; 47.3% women, 49.5% men, 3.3% other, Mage = 38.6, SD = 8.31). We used a preregistered mixed methods approach to examine quantitative predictors (e.g., ideological beliefs, age of own-group ethnic-racial socialization) of discussing discrimination across group boundaries, as well as coding qualitative responses for what types of messages parents use (e.g., color-evasive vs. color-conscious). RESULTS: Asian parents were more likely to discuss anti-Black discrimination than Black parents were to discuss anti-Asian discrimination. Black and Asian parents did not differ in their likelihood of discussing anti-Latinx discrimination. Asian parents were also more likely to acknowledge racism as a major factor underlying anti-Black discrimination, but not for anti-Asian discrimination. Minimization of race was an important correlate for both whether and how Black and Asian parents engaged in collective racial socialization. CONCLUSIONS: These results better characterize when, how, and for whom parents engage in collective racial socialization and highlight how racially minoritized parents may socialize their children to see similarities across racially minoritized groups. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Transdermal Delivery of Pramipexole Using Microneedle Technology for the Potential Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a debilitating neurodegenerative disease primarily impacting neurons responsible for dopamine production within the brain. Pramipexole (PRA) is a dopamine agonist that is currently available in tablet form. However, individuals with PD commonly encounter difficulties with swallowing and gastrointestinal motility, making oral formulations less preferable. Microneedle (MN) patches represent innovative transdermal drug delivery devices capable of enhancing skin permeability through the creation of microconduits on the surface of the skin. MNs effectively reduce the barrier function of skin and facilitate the permeation of drugs. The work described here focuses on the development of polymeric MN systems designed to enhance the transdermal delivery of PRA. PRA was formulated into both dissolving MNs (DMNs) and directly compressed tablets (DCTs) to be used in conjunction with hydrogel-forming MNs (HFMNs). In vivo investigations using a Sprague-Dawley rat model examined, for the first time, if it was beneficial to prolong the application of DMNs and HFMNs beyond 24 h. Half of the patches in the MN cohorts were left in place for 24 h, whereas the other half remained in place for 5 days. Throughout the entire 5 day study, PRA plasma levels were monitored for all cohorts. This study confirmed the successful delivery of PRA from DMNs (Cmax = 511.00 ± 277.24 ng/mL, Tmax = 4 h) and HFMNs (Cmax = 328.30 ± 98.04 ng/mL, Tmax = 24 h). Notably, both types of MNs achieved sustained PRA plasma levels over a 5 day period. In contrast, following oral administration, PRA remained detectable in plasma for only 48 h, achieving a Cmax of 159.32 ± 113.43 ng/mL at 2 h. The HFMN that remained in place for 5 days demonstrated the most promising performance among all investigated formulations. Although in the early stages of development, the findings reported here offer a hopeful alternative to orally administered PRA. The sustained plasma profile observed here has the potential to reduce the frequency of PRA administration, potentially enhancing patient compliance and ultimately improving their quality of life. This work provides substantial evidence advocating the development of polymeric MN-mediated drug delivery systems to include sustained plasma levels of hydrophilic pharmaceuticals.

Unlocking the potential of forage fish to reduce the global burden of disease.

Red meat consumption is associated with an elevated risk of mortality from non-communicable diseases (NCDs). In contrast, forage fish, as highly nutritious, environmentally friendly, affordable, and the most abundant fish species in the ocean, are receiving increasing interest from a global food system perspective. However, little research has examined the impact of replacing red meat with forage fish in the global diet on diet-related NCDs. METHODS: We based our study on datasets of red meat projections in 2050 for 137 countries and forage fish catches. We replaced the red meat consumption in each country with forage fish (from marine habitats), without exceeding the potential supply of forage fish. We used a comparative risk assessment framework to investigate how such substitutions could reduce the global burden of diet-related NCDs in adults. RESULTS: The results of our study show that forage fish may replace only a fraction (approximately 8%) of the world's red meat due to its limited supply, but it may increase global daily per capita fish consumption close to the recommended level. Such a substitution could avoid 0.5-0.75 million deaths and 8-15 million disability-adjusted life years, concentrated in low- and middle-income countries. Forage fish as an alternative to red meat could double (or more) the number of deaths that could be avoided by simply reducing red meat consumption. CONCLUSIONS: Our analysis suggests that forage fish is a promising alternative to red meat. Policies targeting the allocation of forage fish to regions where they are needed, such as the Global South, could be more effective in maximising the potential of forage fish to reduce the global burden of disease.

Is boarding compromising our residents' education? A national survey of emergency medicine program directors.

Background: Boarding patients in the emergency department (ED) potentially affects resident education. Program director (PD) perceptions of the impact of boarding on their trainees have not been previously described. Methods: We surveyed a cross-sectional convenience sample of emergency medicine PDs using a mixed-methods approach to explore their perceptions of how boarding has affected their residents' training. Descriptive data were reported as percentages and differences were calculated using Pearson's chi-square test, with p < 0.05 considered significant. A framework model was used to qualitatively analyze free-text responses. Results: A total of 170 responses were collected, for a response rate of 63%. Most respondents felt that boarding had at least some effect on resident education with 29%, 35%, 18%, and 12% noting "a little," "a moderate amount," "a lot," and "a great deal," respectively, and 5% noting "no effect at all." Respondents perceived a negative impact of boarding on resident education and training, with 80% reporting a "somewhat" or "extremely negative" effect, 18% feeling neutral, and 2% noting a "somewhat positive" effect. Most noted a "somewhat" or "extremely negative" effect on resident education in managing ED throughput (70%) and high patient volumes (66%). Fifty-four percent noted a "somewhat" or "extremely negative" impact on being involved in the initial workup of undifferentiated patients. Thirty-two percent saw a "somewhat" or "extremely positive" effect on learning the management of critically ill patients. Qualitative analysis of challenges, mitigation strategies, and resident feedback emphasized the lack of exposure to managing departmental patient flow, impact on bedside teaching, and need for flexibility in resident staffing. Conclusions: Most PDs agree that boarding negatively affects resident education and identify several strategies to mitigate the impact. These findings can help inform future interventions to optimize resident learning in the complex educational landscape of high ED boarding.

Conditional protein splicing of the Mycobacterium tuberculosis RecA intein in its native host.

The recA gene, encoding Recombinase A (RecA) is one of three Mycobacterium tuberculosis (Mtb) genes encoding an in-frame int ervening pro tein sequence ( intein ) that must splice out of precursor host protein to produce functional protein. Ongoing debate about whether inteins function solely as selfish genetic elements or benefit their host cells requires understanding of interplay between inteins and their hosts. We measured environmental effects on native RecA intein splicing within Mtb using a combination of western blots and promoter reporter assays. RecA splicing was stimulated in bacteria exposed to DNA damaging agents or by treatment with copper in hypoxic, but not normoxic, conditions. Spliced RecA was processed by the Mtb proteasome, while free intein was degraded efficiently by other unknown mechanisms. Unspliced precursor protein was not observed within Mtb despite its accumulation during ectopic expression of Mtb recA within E. coli . Surprisingly, Mtb produced free N-extein in some conditions, and ectopic expression of Mtb N-extein activated LexA in E. coli. These results demonstrate that the bacterial environment greatly impacts RecA splicing in Mtb, underscoring the importance of studying intein splicing in native host environments and raising the exciting possibility of intein splicing as a novel regulatory mechanism in Mtb. Significance Statement: Gene regulation and DNA repair are critical to the success of Mycobacterium tuberculosis , a major bacterial pathogen. The present study found significant interplay between the Mtb host environment and splicing behavior of an integrative intein element within the Mtb RecA protein, which is involved in DNA repair. These findings challenge the concept of inteins as strictly selfish genetic elements by showing that activity of the RecA intein in Mtb is finely tuned to its host and raising the possibility that intein exaptation provides Mtb with additional ways to selectively modulate RecA function.

Improving Medication Management for Inpatients with a Secondary Diagnosis of Parkinson Disease.

ABSTRACT: Patients who have Parkinson disease require individualized medication regimens to optimize care. A review of the medication management of patients admitted to a tertiary care hospital with a secondary diagnosis of Parkinson disease found significant departures from the patients' home regimen. Medication regimens are often altered by health care teams unfamiliar with Parkinson disease-specific care in order to conform to standard hospital medication orders and administration times, potentially resulting in increased patient falls, delirium, and mortality.A nurse-led multidisciplinary team consisting of pharmacy, nursing, informatics, neurology, and quality personnel implemented a quality improvement (QI) project between July 2020 and July 2022 to identify patients with Parkinson disease, including those with a secondary diagnosis and those undergoing deep brain stimulation, and customize medication management in order to reduce length of stay, mortality, falls, falls with harm, and 30-day readmissions. The QI project team also evaluated patient satisfaction with medication management.Among patients with a secondary diagnosis of Parkinson disease, the proportion who had medication histories conducted by a pharmacy staff member increased from a baseline of 53% to more than 75% per month. For all patients with Parkinson disease, those whose medication history was taken by a pharmacy staff member had orders matching their home regimen 89% of the time, whereas those who did not had orders matching the home regimen only 40% of the time. Among patients with a secondary diagnosis of Parkinson disease, the length-of-stay index decreased from a baseline of 1 to 0.94 and observed-to-expected mortality decreased from 1.03 to 0.78. The proportion of patients experiencing a fall decreased from an average of 5% to 4.08% per quarter, while the proportion of patients experiencing a fall with harm decreased from an average of 1% to 0.75% per quarter. The rate of 30-day readmissions decreased from 10.81% to 4.53% per quarter. Patient satisfaction scores were 1.95 points higher for patients who had medication histories taken by pharmacy than for those who did not (5 versus 3.05).

Retrograde Solubility of Methylammonium Lead Iodide in γ-Butyrolactone Does Not Enhance the Uniformity of Continuously Coated Films.

Halide perovskite thin films can be the centerpiece of high-performance solar cells, light-emitting diodes, and other optoelectronic devices if the films are of high uniformity and relatively free of pinholes and other defects. A common strategy to form dense films from solution has been to generate a high density of nuclei by rapidly increasing supersaturation, for example, by timely application of an antisolvent or forced convection. In this work, we examine the role of retrograde solubility, wherein solubility decreases with increasing temperature, as a means of increasing the nucleation density and film coverage of slot-die-coated methylammonium lead iodide (MAPbI3) from γ-butyrolactone (GBL) solution. Coverage was investigated as a function of the substrate temperature and the presence and temperature of an air knife. Results were considered within the framework of the dimensionless modified Biot number, which quantifies the interplay between evaporation and horizontal diffusion. Moderate temperatures and a heated air knife improved film coverage and morphology by enhanced nucleation up to ∼80 °C. However, despite the dense nucleation enabled by retrograde solubility, slow evaporation as a result of the low vapor pressure of GBL, combined with Ostwald ripening at high temperatures, prevented the deposition of void-free, device-quality films. This work has provided a more detailed understanding of the interplay between perovskite processing, solvent parameters, and film morphology and ultimately indicates the obstacles to forming dense, uniform films from solvents with high boiling points even in the presence of rapid nucleation.

Cost-benefit analysis of ecosystem modeling to support fisheries management.

Mathematical and statistical models underlie many of the world's most important fisheries management decisions. Since the 19th century, difficulty calibrating and fitting such models has been used to justify the selection of simple, stationary, single-species models to aid tactical fisheries management decisions. Whereas these justifications are reasonable, it is imperative that we quantify the value of different levels of model complexity for supporting fisheries management, especially given a changing climate, where old methodologies may no longer perform as well as in the past. Here we argue that cost-benefit analysis is an ideal lens to assess the value of model complexity in fisheries management. While some studies have reported the benefits of model complexity in fisheries, modeling costs are rarely considered. In the absence of cost data in the literature, we report, as a starting point, relative costs of single-species stock assessment and marine ecosystem models from two Australian organizations. We found that costs varied by two orders of magnitude, and that ecosystem model costs increased with model complexity. Using these costs, we walk through a hypothetical example of cost-benefit analysis. The demonstration is intended to catalyze the reporting of modeling costs and benefits.

Improved pharmacokinetic and lymphatic uptake of Rose Bengal after transfersome intradermal deposition using hollow microneedles.

The lymphatic system is active in several processes that regulate human diseases, among which cancer progression stands out. Thus, various drug delivery systems have been investigated to promote lymphatic drug targeting for cancer therapy; mainly, nanosized particles in the 10-150 nm range quickly achieve lymphatic vessels after an interstitial administration. Herein, a strategy to boost the lymphotropic delivery of Rose Bengal (RB), a hydrosoluble chemotherapeutic, is proposed, and it is based on the loading into Transfersomes (RBTF) and their intradermal deposition in vivo by microneedles. RBTF of 96.27 ± 13.96 nm (PDI = 0.29 ± 0.02) were prepared by a green reverse-phase evaporation technique, and they showed an RB encapsulation efficiency of 98.54 ± 0.09%. In vitro, RBTF remained physically stable under physiological conditions and avoided the release of RB. In vivo, intravenous injection of RBTF prolonged RB half-life of 50 min in healthy rats compared to RB intravenous injection; the RB half-life in rat body was further increased after intradermal injection reaching 24 h, regardless of the formulation used. Regarding lymphatic targeting, RBTF administered intravenously provided an RB accumulation in the lymph nodes of 12.3 ± 0.14 ng/mL after 2 h, whereas no RB accumulation was observed after RB intravenous injection. Intradermally administered RBTF resulted in the highest RB amount detected in lymph nodes after 2 h from the injection (84.2 ± 25.10 ng/mL), which was even visible to the naked eye based on the pink colouration of the drug. In the case of intradermally administered RB, RB in lymph node was detected only at 24 h (13.3 ± 1.41 ng/mL). In conclusion, RBTF proved an efficient carrier for RB delivery, enhancing its pharmacokinetics and promoting lymph-targeted delivery. Thus, RBTF represents a promising nanomedicine product for potentially facing the medical need for novel strategies for cancer therapy.

Parafilm® M and Strat-M® as skin simulants in in vitro permeation of dissolving microarray patches loaded with proteins.

In vitro permeation studies play a crucial role in early formulation optimisation before extensive animal model investigations. Biological membranes are typically used in these studies to mimic human skin conditions accurately. However, when focusing on protein and peptide transdermal delivery, utilising biological membranes can complicate analysis and quantification processes. This study aims to explore Parafilm®M and Strat-M® as alternatives to dermatomed porcine skin for evaluating protein delivery from dissolving microarray patch (MAP) platforms. Initially, various MAPs loaded with different model proteins (ovalbumin, bovine serum albumin and amniotic mesenchymal stem cell metabolite products) were prepared. These dissolving MAPs underwent evaluation for insertion properties and in vitro permeation profiles when combined with different membranes, dermatomed porcine skin, Parafilm®M, and Strat-M®. Insertion profiles indicated that both Parafilm®M and Strat-M® showed comparable insertion depths to dermatomed porcine skin (in range of 360-430 µm), suggesting promise as membrane substitutes for insertion studies. In in vitro permeation studies, synthetic membranes such as Parafilm®M and Strat-M® demonstrated the ability to bypass protein-derived skin interference, providing more reliable results compared to dermatomed neonatal porcine skin. Consequently, these findings present valuable tools for preliminary screening across various MAP formulations, especially in the transdermal delivery of proteins and peptides.

Determination of the cycle threshold value of the Xpert Xpress SARS-CoV-2/Flu/RSV test that corresponds to the presence of infectious SARS-CoV-2 in anterior nasal swabs.

Despite having high analytical sensitivities and specificities, qualitative SARS-CoV-2 nucleic acid amplification tests (NAATs) cannot distinguish infectious from non-infectious virus in clinical samples. In this study, we determined the highest cycle threshold (Ct) value of the SARS-CoV-2 targets in the Xpert Xpress SARS-CoV-2/Flu/RSV (Xpert 4plex) test that corresponded to the presence of detectable infectious SARS-CoV-2 in anterior nasal swab samples. A total of 111 individuals with nasopharyngeal swab specimens that were initially tested by the Xpert Xpress SARS-CoV-2 test were enrolled. A healthcare worker subsequently collected anterior nasal swabs from all SARS-CoV-2-positive individuals, and those specimens were tested by the Xpert 4plex test, viral culture, and laboratory-developed assays for SARS-CoV-2 replication intermediates. SARS-CoV-2 Ct values from the Xpert 4plex test were correlated with data from culture and replication intermediate testing to determine the Xpert 4plex assay Ct value that corresponded to the presence of infectious virus. Ninety-eight of the 111 (88.3%) individuals initially tested positive by the Xpert Xpress SARS-CoV-2 test. An anterior nasal swab specimen collected from positive individuals a median of 2 days later (range, 0-9 days) tested positive for SARS-CoV-2 by the Xpert 4plex test in 39.8% (39/98) of cases. Of these samples, 13 (33.3%) were considered to contain infectious virus based on the presence of cultivable virus and replication intermediates, and the highest Ct value observed for the Xpert 4plex test in these instances was 26.3. Specimens that yielded Ct values of ≤26.3 when tested by the Xpert 4plex test had a likelihood of containing infectious SARS-CoV-2; however, no infectious virus was detected in specimens with higher Ct values.IMPORTANCEUnderstanding the correlation between real-time PCR test results and the presence of infectious SARS-CoV-2 may be useful for informing patient management and workforce return-to-work or -duty. Further studies in different patient populations are needed to correlate Ct values or other biomarkers of viral replication along with the presence of infectious virus in clinical samples.

Design of a Novel Delivery Efficiency Feedback System for Biphasic Dissolving Microarray Patches Based on Poly(Lactic Acid) and Moisture-Indicating Silica.

Dissolving microarray patches (DMAPs) represent an innovative approach to minimally invasive transdermal drug delivery, demonstrating efficacy in delivering both small and large therapeutic molecules. However, concerns raised in end-user surveys have hindered their commercialization efforts. One prevalent issue highlighted in these surveys is the lack of clear indicators for successful patch insertion and removal time. To address this challenge, a color-change-based feedback system is devised, which confirms the insertion and dissolution of DMAPs, aiming to mitigate the aforementioned problems. The approach combines hydrophilic needles containing model drugs (fluorescein sodium and fluorescein isothiocyanate (FITC)-dextran) with a hydrophobic poly(lactic acid) baseplate infused with moisture-sensitive silica gel particles. The successful insertion and subsequent complete dissolution of the needle shaft are indicated by the progressive color change of crystal violet encapsulated in the silica. Notably, distinct color alterations on the baseplate, observed 30 min and 1 h after insertion for FITC-dextran and fluorescein sodium DMAPs respectively, signal the full dissolution of the needles, confirming the complete cargo delivery and enabling timely patch removal. This innovative feedback system offers a practical solution for addressing end-user concerns and may significantly contribute to the successful commercialization of DMAPs by providing a visualized drug delivery method.

Investigating hair cues as a mechanism underlying Black women's intersectional invisibility.

Children psychologically exclude Black women from their representations of women, but the mechanisms underlying this marginalization remain unclear. Across two studies (N = 129; 49 boys, 78 girls, two gender unreported; 79 White, 27 Black, six Latinx, five Asian, and 12 unreported), the present work tests hair texture as one possible perceptual mechanism by which this might occur. In both studies, children gender-categorized Black, White, and Asian men and women using MouseTracker. Children were slower and had more complex patterns in categorizing Black women when they had textured hair (Study 1A), but not when they had straight hair (Study 1B). Implications for the development of gender as a social category are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Candida auris outbreak at a tertiary care hospital during the COVID-19 pandemic.

BACKGROUND: Candida auris (C auris) is a fungal pathogen that has the potential for environmental persistence leading to outbreaks in health care settings. There has been a worldwide surge in C auris outbreaks during the COVID-19 pandemic. In this report, we describe an outbreak of C auris, its control, patient outcomes, and lessons learned. METHODS: The outbreak occurred in a 600-bed adult academic tertiary care hospital. Contact tracing was initiated immediately after identification of the index case and surveillance testing for C auris was obtained from patients who were exposed to the index case. Infection prevention measures were closely followed. RESULTS: A total of 560 cultures were performed on 453 unique patients between August 2021 and December 2021. Of those, 31 cultures (5.5%) were positive for C auris; 27 (87.1%) were colonized with C auris, while 4 patients developed a clinical infection (12.9%). The secondary attack rate was 6.8% (31/453). The 30-day all-cause mortality rate for all patients who tested positive for C auris was 9.7%. DISCUSSION: C auris can cause protracted outbreaks that result in colonization and invasive infections. Multidisciplinary work to improve adherence to infection prevention measures as well as targeted admission screening are essential to limit outbreaks.

Psychometric properties of the Perceived Stress Scale (PSS-10) in silica-exposed workers from diverse cultural and linguistic backgrounds.

BACKGROUND: The Perceived Stress Scale (PSS-10) has been used in a range of occupational cohorts, but only recently in stone benchtop workers undergoing screening for silicosis. The aim of this study was to compare psychometric properties of the PSS-10 in stone benchtop workers amongst those born overseas or who used an interpreter. METHODS: Stone benchtop workers in Melbourne, Australia completed the PSS-10 as part of their occupational screening for silicosis. Internal consistency was assessed with Cronbach's α for the total score and the positive and negative subscales. Validity was assessed using confirmatory factor analysis (CFA). Analysis was performed for the total group and for subgroups according to sex, interpreter use, overseas-born, and language spoken at home. RESULTS: The results of 682 workers with complete PSS-10 scores were included in analysis. Most participants were male (93%), with mean age 36.9 years (SD 11.4), with just over half (51.6%) born in Australia, 10.1% using an interpreter, and 17.5% using a language other than English at home. Cronbach's α for the overall group (α = 0.878) suggested good internal consistency. DISCUSSION: CFA analysis for validity testing suggested PSS-10 performance was good for both sexes, moderate for country of birth and language spoken at home categories, but poorer for those who used an interpreter. Whilst professional interpreters provide a range of benefits in the clinical setting, the use of translated and validated instruments are important, particularly in cohorts with large numbers of migrant workers. CONCLUSION: This study describes the psychometric properties of the PSS-10 in a population of stone benchtop workers, with good internal consistency, and mixed performance from validity testing across various subgroups.

Novel SmartReservoirs for hydrogel-forming microneedles to improve the transdermal delivery of rifampicin.

Hydrogel-forming microneedles (HF-MNs) are composed of unique cross-linked polymers that are devoid of the active pharmaceutical ingredient (API) within the microneedle array. Instead, the API is housed in a reservoir affixed on the top of the baseplate of the HF-MNs. To date, various types of drug-reservoirs and multiple solubility-enhancing approaches have been employed to deliver hydrophobic molecules combined with HF-MNs. These strategies are not without drawbacks, as they require multiple manufacturing steps, from solubility enhancement to reservoir production. However, this current study challenges this trend and focuses on the delivery of the hydrophobic antibiotic rifampicin using SmartFilm-technology as a solubility-enhancing strategy. In contrast to previous techniques, smart drug-reservoirs (SmartReservoirs) for hydrophobic compounds can be manufactured using a one step process. In this study, HF-MNs and three different concentrations of rifampicin SmartFilms (SFs) were produced. Following this, both HF-MNs and SFs were fully characterised regarding their physicochemical and mechanical properties, morphology, Raman surface mapping, the interaction with the cellulose matrix and maintenance of the loaded drug in the amorphous form. In addition, their drug loading and transdermal permeation efficacy were studied. The resulting SFs showed that the API was intact inside the cellulose matrix within the SFs, with the majority of the drug in the amorphous state. SFs alone demonstrated no transdermal penetration and less than 20 ± 4 µg of rifampicin deposited in the skin layers. In contrast, the transdermal permeation profile using SFs combined with HF-MNs (i.e. SmartReservoirs) demonstrated a 4-fold increase in rifampicin deposition (80 ± 7 µg) in the skin layers and a permeation of approx. 500 ± 22 µg. Results therefore illustrate that SFs can be viewed as novel drug-reservoirs (i.e. SmartReservoirs) for HF-MNs, achieving highly efficient loading and diffusion properties through the hydrogel matrix.

Reduction-Induced Magnetic Behavior in LaFeO3-δ Thin Films.

The effect of oxygen reduction on the magnetic properties of LaFeO3-δ (LFO) thin films was studied to better understand the viability of LFO as a candidate for magnetoionic memory. Differences in the amount of oxygen lost by LFO and its magnetic behavior were observed in nominally identical LFO films grown on substrates prepared using different common methods. In an LFO film grown on as-received SrTiO3 (STO) substrate, the original perovskite film structure was preserved following reduction, and remnant magnetization was only seen at low temperatures. In a LFO film grown on annealed STO, the LFO lost significantly more oxygen and the microstructure decomposed into La- and Fe-rich regions with remnant magnetization that persisted up to room temperature. These results demonstrate an ability to access multiple, distinct magnetic states via oxygen reduction in the same starting material and suggest LFO may be a suitable materials platform for nonvolatile multistate memory.

Chrono-tailored drug delivery systems: recent advances and future directions.

Circadian rhythms influence a range of biological processes within the body, with the central clock or suprachiasmatic nucleus (SCN) in the brain synchronising peripheral clocks around the body. These clocks are regulated by external cues, the most influential being the light/dark cycle, in order to synchronise with the external day. Chrono-tailored or circadian drug delivery systems (DDS) aim to optimise drug delivery by releasing drugs at specific times of day to align with circadian rhythms within the body. Although this approach is still relatively new, it has the potential to enhance drug efficacy, minimise side effects, and improve patient compliance. Chrono-tailored DDS have been explored and implemented in various conditions, including asthma, hypertension, and cancer. This review aims to introduce the biology of circadian rhythms and provide an overview of the current research on chrono-tailored DDS, with a particular focus on immunological applications and vaccination. Finally, we draw on some of the key challenges which need to be overcome for chrono-tailored DDS before they can be translated to more widespread use in clinical practice.

Successful treatment approaches for tumoral calcinosis in children and young people: A condition of diverse pathogenesis.

BACKGROUND: Ectopic calcification is inappropriate biomineralization of soft tissues occurring due to genetic or acquired causes of hyperphosphataemia and rarely in normophosphataemic individuals. Tumoral Calcinosis (TC) is a rare metabolic bone disorder commonly presenting in childhood and adolescence with periarticular extra-capsular calcinosis. Three subtypes of TC have been recognised: primary hyperphosphataemic familial TC (HFTC), primary normophosphataemic familial TC and secondary TC most commonly seen in chronic renal failure. In the absence of established treatment, management is challenging due to variable success rates with medical therapies and recurrence following surgery. AIM: We outline the successful treatment approaches in four children with TC (2 normophosphatemic TC, 2 HFTC) aged 2.5-10 years at initial presentation. CASES: Patient 1 (P1) presented at 10 years with a painless lump behind the right knee, P2 with swelling of the right knee anteriorly at 9 years, P3 and P4 with pain and swelling over the right elbow at 5 and 2.5 years respectively. All patients were of Black African-Caribbean origin and were previously reported to be fit and well with no family history of TC. RESULTS: P1, P2 had normophosphataemic TC and P3, P4 had HFTC with genetically confirmed GALNT3 mutation. All four patients had initial surgical resection with TC confirmed on histology. P1 had complete surgical resection with no recurrence at 27 months post-operatively. P2 had significant overgrowth of the tumour following surgery and was subsequently successfully managed with 25 % topical sodium metabisulphite (total duration of 8 months with a 4 month gap during which there was recurrence). P3 had post-surgical recurrence of TC on the right elbow and a new lesion on left elbow which resolved with oral acetazolamide monotherapy (15-20 mg/kg/day). P4 had recurrence of right elbow lesion following surgery and developed an extensive new hip lesion on sevelamer therapy which resolved completely with additional acetazolamide therapy (18-33 mg/kg/day). Acetazolamide was well tolerated with normal growth for 5 years in P3 and 6.5 years in P4 and no recurrence of lesions. CONCLUSION: The frequent post-surgical recurrence in TC and successful medical therapy on the other hand indicates that medical management as first line therapy should be adopted. Monotherapies with topical 25 % sodium metabisulphite in normophosphataemic and oral acetazolamide in HFTC are effective treatment strategies which are well tolerated.