Human prefrontal cortex gene regulatory dynamics from gestation to adulthood at single-cell resolution.

Human brain development is underpinned by cellular and molecular reconfigurations continuing into the third decade of life. To reveal cell dynamics orchestrating neural maturation, we profiled human prefrontal cortex gene expression and chromatin accessibility at single-cell resolution from gestation to adulthood. Integrative analyses define the dynamic trajectories of each cell type, revealing major gene expression reconfiguration at the prenatal-to-postnatal transition in all cell types followed by continuous reconfiguration into adulthood and identifying regulatory networks guiding cellular developmental programs, states, and functions. We uncover links between expression dynamics and developmental milestones, characterize the diverse timing of when cells acquire adult-like states, and identify molecular convergence from distinct developmental origins. We further reveal cellular dynamics and their regulators implicated in neurological disorders. Finally, using this reference, we benchmark cell identities and maturation states in organoid models. Together, this captures the dynamic regulatory landscape of human cortical development.

Mesothelioma in the pleura, pericardium and peritoneum: Recommendations from the International Collaboration on Cancer Reporting (ICCR).

AIMS: Mesothelioma is a rare malignancy of the serosal membranes that is commonly related to exposure to asbestos. Despite extensive research and clinical trials, prognosis to date remains poor. Consistent, comprehensive and reproducible pathology reporting form the basis of all future interventions for an individual patient, but also ensures that meaningful data are collected to identify predictive and prognostic markers. METHODS AND RESULTS: This article details the International Collaboration on Cancer Reporting (ICCR) process and the development of the international consensus mesothelioma reporting data set. It describes the 'core' and 'non-core' elements to be included in pathology reports for mesothelioma of all sites, inclusive of clinical, macroscopic, microscopic and ancillary testing considerations. An international expert panel consisting of pathologists and a medical oncologist produced a set of data items for biopsy and resection specimens based on a critical review and discussion of current evidence, and in light of the changes in the 2021 WHO Classification of Tumours. The commentary focuses particularly upon new entities such as mesothelioma in situ and provides background on relevant and essential ancillary testing as well as implementation of the new requirement for tumour grading. CONCLUSION: We recommend widespread and consistent implementation of this data set, which will facilitate accurate reporting and enhance the consistency of data collection, improve the comparison of epidemiological data, support retrospective research and ultimately help to improve clinical outcomes. To this end, all data sets are freely available worldwide on the ICCR website (www.iccr-cancer.org/data-sets).

Tretinoin improves the anti-cancer response to cyclophosphamide, in a model-selective manner.

BACKGROUND: Chemotherapy is included in treatment regimens for many solid cancers, but when administered as a single agent it is rarely curative. The addition of immune checkpoint therapy to standard chemotherapy regimens has improved response rates and increased survival in some cancers. However, most patients do not respond to treatment and immune checkpoint therapy can cause severe side effects. Therefore, there is a need for alternative immunomodulatory drugs that enhance chemotherapy. METHODS: We used gene expression data from cyclophosphamide (CY) responders and non-responders to identify existing clinically approved drugs that could phenocopy a chemosensitive tumor microenvironment (TME), and tested combination treatments in multiple murine cancer models. RESULTS: The vitamin A derivative tretinoin was the top predicted upstream regulator of response to CY. Tretinoin pre-treatment induced an inflammatory, interferon-associated TME, with increased infiltration of CD8 + T cells, sensitizing the tumor to subsequent chemotherapy. However, while combination treatment significantly improved survival and cure rate in a CD4+ and CD8+ T cell dependent manner in AB1-HA murine mesothelioma, this effect was model-selective, and could not be replicated using other cell lines. CONCLUSIONS: Despite the promising data in one model, the inability to validate the efficacy of combination treatment in multiple cancer models deprioritizes tretinoin/cyclophosphamide combination therapy for clinical translation.

3 Months without the car in Bielefeld, Germany- a mixed-method study exploring individual motivation to participate in a municipal intervention.

BACKGROUND: Climate change is a major public health issue worldwide. To achieve climate targets and reduce morbidity, a paradigm shift in individual behavior e.g., in mobility, is needed. Municipal interventions can motivate individuals to engage in climate-friendly behavior through different psychological mechanisms. In order for successful interventions, it is necessary to gain better insight from study participants and their reasons for participating in mobility projects (e.g., motivational aspects). MATERIALS AND METHODS: A mixed-methods design was used to evaluate reasons and characteristics of people for participating in an municipal mobility intervention. The quantitative sub-study assesses socioeconomic characteristics, environmental awareness and perceived stress. The qualitative sub-study explores motivation for participation and change, perspectives on car replacement and reasons for car use. RESULTS: Results show that participants (n = 42) are rather high educated and show medium environmental awareness. Participants of the qualitative study part (n = 15) were motiviated to reduce car use already before the intervention and used the intervention as starting point or trial phase. CONCLUSIONS: Urban intervention projects with fitted recruitment strategies and better insights from study participants with the aim to motivate individuals to engage in climate-friendly behavior can help to strengthen sustainability and public health.

Warm spells in winter affect the equilibrium between winter phenotypes.

Each phenotype is a product of the interaction of the genes and the environment. Although winter phenotype in seasonal mammals is heritable, its development may be modified by external conditions. In today's world, global climate change and increasing frequency of unpredictable weather events may affect the dynamic equilibrium between phenotypes. We tested the effect of changes in ambient temperature during acclimation to short photoperiod on the development of winter phenotypes in three generations of Siberian hamsters (Phodopus sungorus). Based on seasonal changes in fur colour, body mass, and expression of daily torpor we distinguished three different winter phenotypes: responding, non-responding, and partially-responding to short photoperiod. We found that warm spells in winter can increase the proportion of non-responding individuals in the population, while stable winter conditions can increase photoresponsiveness among the offspring of non-responders. We conclude that the polymorphism of winter phenotype is an inherent characteristic of the Siberian hamster population but the development of winter phenotype is not fixed but rather a plastic response to the environmental conditions.

An In Vitro Study on the Cytotoxic, Antioxidant, and Antimicrobial Properties of Yamogenin-A Plant Steroidal Saponin and Evaluation of Its Mechanism of Action in Gastric Cancer Cells.

Yamogenin is a steroidal saponin occurring in plant species such as Asparagus officinalis, Dioscorea collettii, Trigonella foenum-graecum, and Agave sp. In this study, we evaluated in vitro cytotoxic, antioxidant, and antimicrobial properties of yamogenin. The cytotoxic activity was estimated on human colon cancer HCT116, gastric cancer AGS, squamous carcinoma UM-SCC-6 cells, and human normal fibroblasts with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The amount of apoptotic and dead AGS cells after treatment with yamogenin was estimated with flow cytometry. Also, in yamogenin-treated AGS cells we investigated the reactive oxygen species (ROS) production, mitochondrial membrane depolarization, activity level of caspase-8 and -9, and gene expression at mRNA level with flow cytometry, luminometry, and RT-PCR, respectively. The antioxidant properties of yamogenin were assessed with DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays. The antimicrobial potential of the compound was estimated on Staphylococcus aureus, Bacillus cereus, Klebsiella pneumoniae, Escherichia coli, Salmonella enterica, Helicobacter pylori, Campylobacter coli, Campylobacter jejuni, Listeria monocytogenes, Lactobacillus paracasei, and Lactobacillus acidophilus bacteria strains. Yamogenin showed the strongest cytotoxic effect on AGS cells (IC50 18.50 ± 1.24 µg/mL) among the tested cell lines. This effect was significantly stronger in combinations of yamogenin with oxaliplatin or capecitabine than for the single compounds. Furthermore, yamogenin induced ROS production, depolarized mitochondrial membrane, and increased the activity level of caspase-8 and -9 in AGS cells. RT-PCR analysis revealed that this sapogenin strongly up-regulated TNFRSF25 expression at the mRNA level. These results indicate that yamogenin induced cell death via the extrinsic and intrinsic way of apoptosis. Antioxidant study showed that yamogenin had moderate in vitro potential (IC50 704.7 ± 5.9 µg/mL in DPPH and 631.09 ± 3.51 µg/mL in ABTS assay) as well as the inhibition of protein denaturation properties (with IC50 1421.92 ± 6.06 µg/mL). Antimicrobial test revealed a weak effect of yamogenin on bacteria strains, the strongest one being against S. aureus (with MIC value of 350 µg/mL). In conclusion, yamogenin may be a potential candidate for the treatment and prevention of gastric cancers.

New Polymeric Hydrogels with Cannabidiol and α-Terpineol as Potential Materials for Skin Regeneration-Synthesis and Physicochemical and Biological Characterization.

Dermatology and cosmetology currently prioritize healthy, youthful-looking skin. As a result, research is being conducted worldwide to uncover natural substances and carriers that allow for controlled release, which could aid in the battle against a variety of skin illnesses and slow the aging process. This study examined the biological and physicochemical features of novel hydrogels containing cannabidiol (CBD) and α-terpineol (TER). The hydrogels were obtained from ε-caprolactone (CL) and poly(ethylene glycol) (PEG) copolymers, diethylene glycol (DEG), poly(tetrahydrofuran) (PTHF), 1,6-diisocyanatohexane (HDI), and chitosan (CHT) components, whereas the biodegradable oligomers were synthesized using the enzyme ring-opening polymerization (e-ROP) method. The in vitro release rate of the active compounds from the hydrogels was characterized by mainly first-order kinetics, without a "burst release". The antimicrobial, anti-inflammatory, cytotoxic, antioxidant, and anti-aging qualities of the designed drug delivery systems (DDSs) were evaluated. The findings indicate that the hydrogel carriers that were developed have the ability to scavenge free radicals and impact the activity of antioxidant enzymes while avoiding any negative effects on keratinocytes and fibroblasts. Furthermore, they have anti-inflammatory qualities by impeding protein denaturation as well as the activity of proteinase and lipoxygenase. Additionally, their ability to reduce the multiplication of pathogenic bacteria and inhibit the activity of collagenase and elastase has been demonstrated. Thus, the developed hydrogel carriers may be effective systems for the controlled delivery of CBD, which may become a valuable tool for cosmetologists and dermatologists.

Medicinal Anti-Inflammatory Patch Loaded with Lavender Essential Oil.

Transdermal drug delivery offers a promising alternative for administering medications like ibuprofen, known for its analgesic and anti-inflammatory properties, with reduced gastrointestinal side effects compared to oral administration. This study explored the potential synergistic effects of combining ibuprofen with lavender essential oil (LEO) in transdermal patches. The composition of LEO was analyzed, revealing predominant compounds such as linalyl acetate and linalool, which are known for their analgesic and anti-inflammatory properties. The physicochemical properties of the patches were investigated, indicating improved cohesion with the addition of LEO. Additionally, thermal stability assessments demonstrated enhanced stability with LEO incorporation with an increase in onset decomposition temperature from 49.0 to 67.9 °C. The antioxidant activity of patches containing LEO was significantly higher with a free radical scavenging ability of 79.13% RSA compared to 60% RSA in patches without LEO. Release and permeation studies showed that patches with LEO exhibited an increased permeation of ibuprofen through the skin with 74.40% of the drug released from LEO-containing patches compared to 36.29% from patches without LEO after 24 h. Moreover, the permeation rate was notably faster with LEO, indicating quicker therapeutic effects. The inclusion of LEO in transdermal patches containing ibuprofen holds promise for enhancing drug delivery efficiency and therapeutic effectiveness, offering a potential strategy for improved pain management with reduced side effects.

Investigating the Anti-Inflammatory Properties and Skin Penetration Ability of Cornelian Cherry (Cornus mas L.) Extracts.

Plant extracts can be a valuable source of biologically active compounds in many cosmetic preparations. Their effect depends on the phytochemicals they contain and their ability to penetrate the skin. Therefore, in this study, the possibility of skin penetration by phenolic acids contained in dogwood extracts of different fruit colors (yellow, red, and dark ruby red) prepared using different extractants was investigated. These analyses were performed using a Franz chamber and HPLC-UV chromatography. Moreover, the antioxidant properties of the tested extracts were compared and their impact on the intracellular level of free radicals in skin cells was assessed. The cytotoxicity of these extracts towards keratinocytes and fibroblasts was also analyzed and their anti-inflammatory properties were assessed using the enzyme-linked immunosorbent assay (ELISA). The analyses showed differences in the penetration of individual phenolic acids into the skin and different biological activities of the tested extracts. None of the extracts had cytotoxic effects on skin cells in vitro, and the strongest antioxidant and anti-inflammatory properties were found in dogwood extracts with dark ruby red fruits.

Kombucha as a Potential Active Ingredient in Cosmetics-An Ex Vivo Skin Permeation Study.

Kombucha is a non-alcoholic beverage, that is increasingly used in the cosmetic industry. The available literature reports the positive effects of kombucha on the skin, in particular its antioxidant action. However, there is a lack of information on skin permeation and the accumulation of active ingredients showing such effects. Skin aging is largely dependent on oxidative stress, therefore in our study we assessed the ex vivo permeation of two types of kombucha (green and black tea) through porcine skin. The antioxidant activity (DPPH, ABTS, FRAP methods) and total polyphenol content of these extracts were determined before and after permeation testing. Moreover, the content of selected phenolic acids as well as caffeine was assessed. Skin permeation was determined using a Franz diffusion cell. The antioxidant activity of both Kombuchas was found to be high. In addition, gallic acid, chlorogenic acid, protocatechuic acid, coumaric acid, m-hydroxybenzoic acid, and caffeine were identified. A 24-h ex vivo study showed the permeation of some phenolic acids and caffeine and their accumulation in the skin. Our results confirm the importance of studying the skin permeation of what are still little known ingredients in cosmetic preparations. Evaluation of the accumulation of these ingredients can guarantee the efficacy of such preparations.

Clinical Perspective on Human Immunodeficiency Virus Care of Ukrainian War Refugees in Poland.

BACKGROUND: The Russian invasion of Ukraine forced migration for safety, protection, and assistance. Poland is the primary sheltering country for Ukrainian refugees, providing support including medical care, which resulted in the rapid ∼15% increase in the number of followed-up people with human immunodeficiency virus (HIV) (PWH) in the country. Here, we present the national experience on HIV care provided for refugees from Ukraine. METHODS: Clinical, antiretroviral, immunological, and virologic data from 955 Ukrainian PWH entering care in Poland since February 2022 were analyzed. The dataset included both antiretroviral-treated (n = 851) and newly diagnosed (n = 104) patients. In 76 cases, protease/reverse transcriptase/integrase sequencing was performed to identify drug resistance and subtype. RESULTS: Most (70.05%) of the patients were female, with a predominance of heterosexual (70.3%) transmissions. Anti-hepatitis C antibody and hepatitis B antigen were present in 28.7% and 2.9% of the patients, respectively. A history of tuberculosis was reported in 10.1% of cases. Among previously treated patients, the viral suppression rate was 89.6%; 77.3% of newly HIV diagnosed cases were diagnosed late (with lymphocyte CD4 count <350 cells/µL or AIDS). The A6 variant was observed in 89.0% of sequences. Transmitted mutations in the reverse transcriptase were found in 15.4% treatment-naive cases. Two patients with treatment failure exhibited multiclass drug resistance. CONCLUSIONS: Migration from Ukraine influences the characteristics of HIV epidemics in Europe, with an increase in the proportion of women and hepatitis C coinfected patients. Antiretroviral treatment efficacy among previously treated refugees was high, with new HIV cases frequently diagnosed late. The A6 subtype was the most common variant.

Carer preparedness improved by providing a supportive educational intervention for carers of patients with high-grade glioma: RCT results.

BACKGROUND: High-grade glioma (HGG) is a rapidly progressing and debilitating disease. Family carers take on multiple responsibilities and experience high levels of distress. We aimed to deliver a nurse-led intervention (Care-IS) to carers to improve their preparedness to care and reduce distress. METHODS: We conducted a randomised controlled trial (ACTRN:12612001147875). Carers of HGG patients were recruited during patients' combined chemoradiation treatment. The complex intervention comprised four components: (1) initial telephone assessment of carer unmet needs; (2) tailored hard-copy resource folder; (3) home visit; and, (4) monthly telephone support for up to 12 months. Primary outcomes included preparedness for caregiving and distress at 2, 4, 6 and 12 months. Intervention effects were estimated using linear mixed models which included a time by group interaction. Secondary outcomes included anxiety, depression, quality of life, carer competence and strain. RESULTS: We randomised 188 carers (n = 98 intervention, n = 90 control). The intervention group reported significantly higher preparedness for caregiving at 4 months (model ß = 2.85, 95% CI 0.76-4.93) and all follow-up timepoints including 12 months (model ß = 4.35, 95% CI 2.08-6.62), compared to the control group. However, there was no difference between groups in carer distress or any secondary outcomes. CONCLUSIONS: This intervention was effective in improving carer preparedness. However, carer distress was not reduced, potentially due to the debilitating/progressive nature of HGG and ongoing caring responsibilities. Future research must explore whether carer interventions can improve carer adjustment, self-efficacy and coping and how we support carers after bereavement. Additionally, research is needed to determine how to implement carer support into practice.

Synthesis, thermal evolution and magnetic investigations of SBA-15 silica functionalized with anchored iron phosphonate molecules.

In the current work, we report on the synthesizing of a series of novel nanocomposite materials obtained by functionalizing the SBA-15 silica matrix with anchored iron phosphonate molecules and the following thermal treatment. The obtained results reveal the formation of a unique amorphic layer of Fe-based compounds on the surface of silica walls of SBA-15 channels as a result of the organic groups' decomposition after moderate thermal treatment. Due to their unique structure, represented in an active Fe-containing amorphous coating spread over a large surface area, these materials are of great interest for their potential applications in fields such as catalysis, adsorption, and non-linear optics. The obtained materials remain amorphous, preserving the SBA-15 mesoporous structure up to temperatures of approximately 800 °C, after which the partial melting of the silica backbone is observed with the simultaneous formation of nanocrystals inside the newly-formed glassy mass. All obtained materials were characterized using such techniques as thermogravimetry, transmission and scanning electron microscopy combined with energy dispersive x-ray spectroscopy mapping, Raman spectroscopy, N2sorption analysis, x-ray diffraction, x-ray photoelectron spectroscopy, Mössbauer spectroscopy, and SQUID measurements.

An evidence-base for the implementation of hospital-based palliative care programs in routine cancer practice: A systematic review.

BACKGROUND: Despite global support, there remain gaps in the integration of early palliative care into cancer care. The methods of implementation whereby evidence of benefits of palliative care is translated into practice deserve attention. AIM: To identify implementation frameworks utilised in integrated palliative care in hospital-based oncology services and to describe the associated enablers and barriers to service integration. DESIGN: Systematic review with a narrative synthesis including qualitative, mixed methods, pre-post and quasi experimental designs following the guidance by the Centre for Reviews and Dissemination (PROSPERO registration CRD42021252092). DATA SOURCES: Six databases searched in 2021: EMBASE, EMCARE, APA PsycINFO, CINAHL, Cochrane Library and Ovid MEDLINE searched in 2023. Included were qualitative or quantitative studies, in English language, involving adults >18 years, and implementing hospital-based palliative care into cancer care. Critical appraisal tools were used to assess the quality and rigour. RESULTS: Seven of the 16 studies explicitly cited the use of frameworks including those based on RE-AIM, Medical Research Council evaluation of complex interventions and WHO constructs of health service evaluation. Enablers included an existing supportive culture, clear introduction to the programme across services, adequate funding, human resources and identification of advocates. Barriers included a lack of communication with the patients, caregivers, physicians and palliative care team about programme goals, stigma around the term 'palliative', a lack of robust training, or awareness of guidelines and undefined staff roles. CONCLUSIONS: Implementation science frameworks provide a method to underpin programme development and evaluation as palliative care is integrated within the oncology setting.

Associations between postmigration living situation and symptoms of common mental disorders in adult refugees in Europe: updating systematic review from 2015 onwards.

BACKGROUND: Refugees and asylum seekers have a high prevalence of psychiatric disorders such as post-traumatic stress disorder (PTSD), anxiety, and depression. The postmigration context inheres different risk and protective factors for mental health of refugees and asylum seekers in host countries. We conducted a systematic review to update knowledge on the association between characteristics of the postmigration living situation (PMLS) and mental health outcomes in Europe since 2015. METHODS: We searched in five databases according to the PRISMA statement. From a total of 5,579 relevant studies published in 2015-22, 3,839 were included for title and abstract screening, and 70 full texts screened for eligibility. Out of these, 19 studies on refugees and asylum seekers conducted in European countries after 2014 were included in this systematic review. The quality of studies was assessed by using the Mixed Methods Appraisal Tool (MMAT) - version 2018. We performed a narrative synthesis using the four layers of the social determinants of health framework. RESULTS: A wide range of risk and protective factors for mental health in the PMLS were identified as exposure measures, which included individual factors (e.g., language skills), social and community networks (e.g., family concerns, loneliness and social support, discrimination), living and working conditions (e.g., legal status, duration of residence, unemployment and financial hardship, housing) as well as general socio-economic, cultural and environmental factors (e.g., social status, acculturation). We found postmigration stressors are positively associated with symptoms of depression, anxiety, and PTSD, albeit not consistently so. Especially, the general socio-economic, cultural and environmental factors showed weak associations with mental health. CONCLUSIONS: Heterogenous study characteristics likely explain the inconsistent associations between characteristics of the PMLS and mental health outcomes. However, broken down in its component layers, most risk and protective factors of the PMLS were significantly associated with symptoms of mental disorders showing the same direction of association across the included studies, while the association between some stressors or resources of the PMLS and mental health turns out to be less homogeneous than expected. Characteristics of the PMLS contribute to the high prevalence of mental diseases of refugees and asylum seekers. Disadvantages in general socio-economic conditions, living and working conditions, in access to social and community networks need to be redressed, in addition to better access to health care.

Bereavement outcomes of carers of patients with high grade glioma: Experiences of support before and after the death.

Carers of people with High Grade Glioma (HGG) completed a survey assessing their anxiety, depression, and grief in addition to open-ended questions exploring their experiences of support pre- and post-death (N = 25). One-third reported borderline or clinical levels of anxiety, depression, and grief related distress. Given the poor prognosis and rapid deterioration of patients with HGG, the findings highlight the importance of sensitive communication about prognosis early in the disease trajectory, information tailored to disease stage, the initiation of a referral to psychological support services, and timely discussions about the preferred place of care and death.

Enhancing Transdermal Delivery: Investigating the Impact of Permeation Promoters on Ibuprofen Release and Penetration from Medical Patches-In Vitro Research.

This study investigated the impact of various enhancers on permeation through the skin and accumulation in the skin from acrylic pressure-sensitive adhesive-based drug-in-adhesives matrix-type transdermal patches. Eleven patches, each containing a 5% enhancer of permeation, encompassing compounds such as salicylic acid, menthol, urea, glycolic acid, allantoin, oleic acid, Tween 80, linolenic acid, camphor, N-dodecylcaprolactam, and glycerin, were developed. Ibuprofen (IBU) was the model active substance, a widely-used non-steroidal anti-inflammatory drug. The results were compared to patches without enhancers and commercial preparations. The study aimed to assess the effect of enhancers on IBU permeability. The adhesive properties of the patches were characterised, and active substance permeability was tested. The findings revealed that patches with 5% allantoin exhibited the highest IBU permeability, approximately 2.8 times greater than patches without enhancers after 24 h. These patches present a potential alternative to commercial preparations, highlighting the significant impact of enhancers on transdermal drug delivery efficiency.

Microwave Irradiation vs. Structural, Physicochemical, and Biological Features of Porous Environmentally Active Silver-Silica Nanocomposites.

Heavy metals and other organic pollutants burden the environment, and their removal or neutralization is still inadequate. The great potential for development in this area includes porous, spherical silica nanostructures with a well-developed active surface and open porosity. In this context, we modified the surface of silica spheres using a microwave field (variable power and exposure time) to increase the metal uptake potential and build stable bioactive Ag2O/Ag2CO3 heterojunctions. The results showed that the power of the microwave field (P = 150 or 700 W) had a more negligible effect on carrier modification than time (t = 60 or 150 s). The surface-activated and silver-loaded silica carrier features like morphology, structure, and chemical composition correlate with microbial and antioxidant enzyme activity. We demonstrated that the increased sphericity of silver nanoparticles enormously increased toxicity against E. coli, B. cereus, and S. epidermidis. Furthermore, such structures negatively affected the antioxidant defense system of E. coli, B. cereus, and S. epidermidis through the induction of oxidative stress, leading to cell death. The most robust effects were found for nanocomposites in which the carrier was treated for an extended period in a microwave field.

Exploring Alkyl Ester Salts of L-Amino Acid Derivatives of Ibuprofen: Physicochemical Characterization and Transdermal Potential.

This research presents novel ibuprofen derivatives in the form of alkyl ester salts of L-amino acids with potential analgesic, anti-inflammatory, and antipyretic properties for potential use in transdermal therapeutic systems. New derivatives of (RS)-2-[4-(2-methylpropyl)phenyl]propionic acid were synthesized using hydrochlorides of alkyl esters (ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, and pentyl) of L-glutamine. These were further transformed into alkyl esters of L-amino acid ibuprofenates through neutralization and protonation reactions. Characterization involved spectroscopic methods, including nuclear magnetic resonance and Fourier-transform infrared spectroscopy. Various physicochemical properties were investigated, such as UV-Vis spectroscopy, polarimetric analysis, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, water solubility, octanol/water partition coefficient, and permeability through pig skin using Franz diffusion cells. The research confirmed the ionic structure of the obtained hydrochlorides of alkyl esters of L-amino acids and ibuprofenates of alkyl esters of L-glutamic acid. It revealed significant correlations between ester chain length and thermal stability, crystallinity, phase transition temperatures, lipophilicity, water solubility, skin permeability, and skin accumulation of these compounds. Compared to the parent ibuprofen, the synthesized derivatives exhibited higher water solubility, lower lipophilicity, and enhanced skin permeability. This study introduces promising ibuprofen derivatives with improved physicochemical properties, highlighting their potential for transdermal therapeutic applications. The findings shed light on the structure-activity relationships of these derivatives, offering insights into their enhanced solubility and skin permeation, which could lead to more effective topical treatments for pain and inflammation.

[Experiences of people with refugee backgrounds in utilising healthcare in Germany-findings from a qualitative study]. / Erfahrungen von Menschen mit Fluchtgeschichte bei der Inanspruchnahme der Gesundheitsversorgung in Deutschland ­ Erkenntnisse einer qualitativen Studie.

BACKGROUND: Refugees and asylum seekers face a variety of legal, structural, administrative, cultural and linguistic barriers in accessing healthcare. However, there is currently a lack of available data on the health needs of refugees and asylum seekers. In particular, their subjective experience in accessing healthcare has not been considered sufficiently. AIM OF THE STUDY: This paper explores the subjective experiences of refugees and asylum seekers in accessing and using healthcare. Strategies for dealing with potential challenges are presented. METHODS: The recruitment of interview partners was based on a quantitative cross-sectional study collected as part of a study on the health of refugees (FlüGe health study). Persons who agreed to be contacted again were contacted by telephone. A heterogeneous sub-sample (n = 18) with regard to age, gender, nationality, health status and utilisation behaviour was interviewed using interpreter-supported problem-centred interviews. Data were analysed using a deductive-inductive approach. RESULTS AND DISCUSSION: The migration-insensitive healthcare for refugees and asylum seekers is characterised by language barriers, disorientation, experiences of rejection, mistreatment and structural barriers. Experiences of foreignness in the healthcare system can lead to delayed care seeking or underusage of healthcare systems. At the same time, individual strategies by refugees, asylum seekers and healthcare providers are used in order to meet these challenges.