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Bergenia crassifolia extract-loaded nanogel to untangle the web of psoriasis: Characterization and In Vivo evaluation in an IMQ-induced rat model
Published: 11 November 2024 by MDPI in The 2nd International Electronic Conference on Clinical Medicine session Dermatology

Background: The high surface-to-volume ratio, tiny size, general non-toxicity, and ease of functionalization of nanostructured lipid carriers make them an excellent option for topical drug delivery systems.

Methods: The NLC of Bergenia crassifolia extract composed of soy wax as a solid lipid and Sea buckthorn seed oil were prepared using the hot melt method and embedded in a topical gel. The Box–Behnken experimental design was run and the gels were prepared using 1% carbopol-934. The characterization of NLC and nanogels was carried out using bergenin as a biomarker. A mouse model of imiquimod-induced psoriasis was used to carry out our in vivo study.

Results: The characterization of NLC showed the encapsulation of the extract. Studies on histopathology showed that the produced nanogel had a potentially effective anti-psoriatic effect. The findings indicated that, in comparison to plane extract gel, nanogel demonstrated anti-psoriatic action in a shorter amount of time. Additionally, the nanogel showed prolonged drug release for 12 hours and decreased the inflammatory markers IL-23 and IL-17 associated with psoriasis.

Conclusion: Nanogel improves penetration, deposits drugs deeper into the skin layers, and reduces systemic absorption compared to extracts, highlighting the potential of nanosizing to enhance biological activities. Dermatokinetics and preclinical findings show the downregulation of inflammatory mediators IL-23 and IL-17. The skin irritation study score indicated that the gel was not irritating. The results show that the nanogel is an effective and safe carrier for plant extracts. Clinical studies are needed to evaluate the efficacy of this treatment as an alternative or supplement to conventional treatments for psoriasis.

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In vitro studies on the use of Extremely Low Frequency (ELF) Electromagnetic Fields as a meansof increasing the effectiveness of anticancer drugs

Introduction

Extremely low frequency (ELF) electromagnetic fields (EFs) represent an innovative meansof treating cancer. They affect various biological processes in cells, such as proliferation, metabolism, and cell cycle, which play a key role in the development of cancer cells. Intercellular interactions based on the EF regulate cell migration and morphogenesis. These processes are closely related to the function of the centrosome and intercellular communication. EFs can increase apoptosis and inhibit the angiogenesis and proliferation of tumor cells.

Methods

In order to investigate the effect of ELFs on the action of anticancer drugs, a device was developed that allows for the assessment of the effect on cell cultures on various cancer cell lines (including those taken from the patient) and the use of anticancer drugs in the appropriate concentration. It is possible to investigate the effect of the selected EF intensity in the ELF range to determine the optimal time of field exposure.

Results

The initial evaluation of device performance and the determination of EF parameters were performed on three human cancer cell lines (LoVo, MC7, and A431) treated with doxorubicin. In relation to the EF parameters, the operating range of the field with a frequency of 50 Hz and an induction of 1.25 mT was established. The EF distribution inside the solenoid was examined. Only cells within an area no greater than 5 cm from the central point of the solenoid may be considered as having been subjected to uniform exposure with non-uniformities not exceeding +10%.

Conclusion

The described method allows for an effective and fast way of checking the influence of EF on the pharmacological effect of the drug for a given type of cancer. This model can thus help in selecting the appropriate EF parameters, allowing for a reduction in the cytostatic dose while maintaining the effectiveness of the therapy.

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EphB4 knockdown inhibits the growth and epithelial–mesenchymal transition of gastric cancer cells and triggers death via the PI3K/AKT pathway.
Published: 11 November 2024 by MDPI in The 2nd International Electronic Conference on Clinical Medicine session Immunology

Introduction:

The management of gastric cancer is challenging due to the complexities associated with its therapy and nursing care. This work aimed to elucidate the functions and processes of erythropoietin-producing hepatocellular carcinoma Receptor B4 (EphB4) in gastric cancer.

Methods:

EphB4 expression in gastric cancer tissues and cell lines was assessed using RT-qPCR and Western blotting techniques. The impact of EphB4 on cell growth, programmed cell death, transformation of cells from an epithelial to a mesenchymal state, and the PI3K/AKT signaling pathway in gastric cancer cells was also examined by MTT tests, flow cytometry, and Western blotting.

Results:

EphB4 expression was significantly increased (P<0.05) in gastric cancer tissues and cells. At the same time, downregulation of EphB4 significantly suppressed (P<0.001) gastric cancer cell proliferation, triggered apoptosis, reduced the expression of proteins associated with epithelial–mesenchymal transition (EMT), and exerted a regulatory influence by inhibiting the PI3K/AKT signaling pathway. Furthermore, the results revealed that the over-expression of EphB4 had a substantial impact on the proliferation of (P<0.001) gastric cancer cells, suppressing apoptosis, reducing the expression of E-cadherin, increasing the expression of N-cadherin, and activating the PI3K/AKT signaling pathway. The suppression of EphB4 significantly impeded (P<0.001) the cell growth and epithelial–mesenchymal transition (EMT) process while promoting apoptosis in gastric cancer cells.

Conclusion:

These discoveries provide new perspectives on the involvement of EphB4 in the progression of gastric cancer. All this makes EphB4 a promising target for future study in gastric cancer.

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Is exercise fun? Virtual-reality boxing versus traditional cardio to improve in-task valance and post-exercise enjoyment.
, , ,

Given the overwhelming literature on the beneficial effects of exercise, it is surprising that many individuals do not meet current physical activity guidelines. Among the most often cited reasons for nonadherence to exercise are lack of time and lack of enjoyment. However, recent technology has provided a new mode of exercise that could change that. PURPOSE: We plan to compare in-task valance during and enjoyment after a bout of moderate-intensity continuous exercise (MICE) and virtual-reality boxing (VRB). METHODS: Using a within-subject randomized design, the participants [N= 20, 8 females; age (M ± SD); 26.1 ± 7.2 yrs; BMI (M ± SD); 26.4 ± 5.8] completed a 5 min warm-up, 20 min of MICE and VRB workout, and a 5 min cool-down. In-task valance, heart rate, and rating of perceived exertion (RPE) were assessed during each condition, and enjoyment was assessed immediately after each condition. Results: The participants reported more positive in-task valence [Cohen’s d= .59] and greater post-exercise enjoyment [Cohen’s d= 1.76] during VRB relative to MICE. Further, the participants reported higher RPE [Cohen’s d= .53] and heart rates [Cohen’s d= .52] during VRB. Conclusion: Virtual-reality boxing resulted in significantly greater in-task valence and post-exercise enjoyment relative to traditional cardio. As both in-task valence and enjoyment have been linked to exercise adherence, virtual-reality exercise should be considered as a means to increase exercise adherence.

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Meeting the health needs of people fleeing Ukraine: Evidence from the Polish Nationwide General Hospital Morbidity Study, 2022–2023

Introduction

Refugee children, adults, and elderly individuals who have fled the war in Ukraine and stayed in Poland are still in need of our support. The combined impact of warfare and displacement presents a significant threat to their health, making them an especially vulnerable population.

This study aimed to evaluate the leading cause of hospital admissions among Ukrainian migrants and war refugees receiving hospital care in Poland in the years 2022-2023 in order to identify their changing health needs.

Methods

This study is based on the analysis of hospital admission records of Ukrainian patients retrieved from the Nationwide General Hospital Morbidity Study conducted by the National Institute of Public Health NIH-NRI. Two periods after the outbreak of the war were analyzed: 24.02.2022-31.12.2022 and 01.01.2023-31.12.2023.

Results

In the study period, 10 440 Ukrainians (including 5051 children) were hospitalized in Poland, 68.4% of whom were admitted to hospital in 2022.

The most frequently reported hospital events among Ukrainian migrants and war refugees in 2022, accounting for 12.9%, were pregnancy, childbirth, and the puerperium (O00-O99). Injury, poisoning and certain other consequences of external causes (S00-T88) were the second most frequently reported causes of hospitalization (10.7%). The third most significant reason for hospital admission was infectious and parasitic diseases (A00-B99), at 10.6%.

In 2023, the incidence of health problems among migrants and war refugees that resulted in hospital admissions changed, with pregnancy, childbirth, and the puerperium (O00-O99) being the most common (21.0%), followed by neoplasms (C00-D49), at 16.8%, and injury, poisoning and certain other consequences of external causes (S00-T88), at 9.5%.

Conclusions

Our research findings may contribute to informing health policy planning and facilitating the provision of adequate healthcare in host countries. Health services should be sensitive to the changing needs of migrants and war refugees to optimize their health and well-being.

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Nanoparticles for Enhanced Drug Delivery to Hair Follicles: A Comprehensive Review
Published: 11 November 2024 by MDPI in The 2nd International Electronic Conference on Clinical Medicine session Dermatology

Nanoparticles (NPs) have emerged as attractive vehicles for targeted medication delivery to hair follicles (HFs), providing increased therapeutic efficacy while minimizing systemic side effects. This comprehensive review investigates the various applications of NPs in HF-targeted drug delivery, emphasizing polymeric, lipid, metallic, and other specialized NPs. Key physicochemical features such as size and content influence NP penetration depth and follicular targeting efficacy. NPs ranging in size from 400 nm to 700 nm penetrate HFs most successfully, with polymeric and lipid NPs showing particular promise because of their biocompatibility and customised release patterns. Drug delivery using polymeric nanoparticles (NPs) is a reliable method, and finasteride (FIN) and dutasteride for alopecia treatments have been effectively administered by NPs like poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA). Lipid nanoparticles (NPs), such as solid lipid NPs (SLNs) and nanostructured lipid carriers (NLCs), provide long-term drug release and have a preference for high-sebum HF settings, which improves follicular absorption. Deeper penetration into HFs is made possible by the special qualities of metallic NPs, such as gold and iron oxide NPs, through treatments like plasmonic heating and magnetic targeting. Effective medication distribution to the hair bulb and supra bulbar region—critical areas for controlling hair growth cycles—remains a challenge. Techniques like surface modification with bioactive compounds and NP size optimization show potential for improving NP delivery to these deep HF areas. To ensure the safe and efficient treatment of hair diseases, more research is required despite breakthroughs to optimise NP formulations for therapeutic uses. The promise of NPs to transform therapeutic methods for alopecia and other HF-related illnesses is highlighted in this review, which compiles recent developments and obstacles in NP-based drug delivery to HFs.

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Multidimensional Analysis Of Advanced-Stage Huntington's Disease From Neurocognitive And Psychofunctional Perspectives With Morphometric Correlations: Case Series

Background: Huntington's disease (HD) is a progressive neurodegenerative monogenic disorder, and its multifaceted clinical and radiological analysis correlations are not yet understood. We aim to evaluate advanced-stage HD patients for multidimensional clinical deterioration with objective scales and correlate this with morphometric-based measurements.

Materials and Methods: Ten advanced-stage HD patients evaluated with the Unified Huntington's Disease Rating Scale (UHDRS) were subjected to psychofunctional assessment for behavioral and neurocognitive decline, total functional capacity (TFC), and functional assessment scale (FAS) for functional determination. In the morphometric assessment, bicaudate ratio (BCR), bi-frontal ratio (BFR), frontal horn area (FHA), frontal horn ratio to intercaudate distance (FH/CC), and caudate volume and caudate volume ratio (CVR) were analyzed and correlated with relevant parameters.

Results: The most frequent functional decline was observed for occupational and financial ability in UHDRS TFC (5.60±2.27), social/financial engagement, and self-care impairment in the FAS (11.10±3.48). Cognitive decline was especially prevalent in quick thinking and responding to stimuli on time and to a sufficient extent. Caudate volume loss was more severe on the right-hand side (6.50±1.18) and inferior sections (21.65±7.30). A negative correlation was found between intercaudate distance and the verbal fluency test (rho=-0.775). The Parkinson's disease sleep scale and intercaudate distance were negatively correlated (rho=-0.559), and a positive correlation was found for the bi-frontal distance/caudate distance (rho=0.559). There was a negative correlation between the Questionnaire for Impulsive–Compulsive Disorders in Parkinson's Disease-Rating Scale, the Hamilton Depression Rating Scale, and the Hamilton Anxiety Rating Scale and FHD (rho=-0.671, rho=0.61 and rho=0.571, respectively).

Conclusion: In light of the current findings, caudate atrophy is an important indicator of cognito-functional disability, especially in terms of verbal ability. The right hemisphere seems to be more vulnerable to neurodegenerative processes, and mood disorders appear to be related explicitly to right frontal lobe degeneration. Psychofunctional deterioration may begin years before clinical diagnosis, so HD should be considered in the differential diagnosis of aberrant psychofunctional deterioration in young patients.

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Effectiveness of Hybrid Assertive Community Treatment in Rural Greece: Improving Outcomes for Severe Mental Illness Patients
, , , , , , ,

Introduction:

In rural areas, Modified Assertive Community Treatment (ACT) could prove pivotal in managing severe mental illness (SMI) in patients that are difficult to engage in community care. The objective of the present study was to assess the impact of a hybrid ACT team on SMI patients' hospitalizations, their length of hospital stay, their symptomatology, and their functioning within a rural community treatment setting in Greece.

Methods:

Expanding the services of a well-established Mobile Mental Health Unit, the hybrid ACT team delivers home-based care for SMI patients in a rural area of northwest Greece. This 3-year prospective, mirror-image, pre–post observational study evaluates patients' symptomatology, functioning, and overall outcome using three validated scales: the Brief Psychiatric Rating Scale (BPRS), the Global Assessment of Functioning Scale (GAF), and the Health of the Nation Outcome Scale (HοNOS).

Results:

Among the 23 enrolled patients (mean age: 52.4 years; mean age of disease onset: 23.5 years; mean hospitalizations: 10.74), voluntary and involuntary hospitalizations decreased by nearly 80% over a 16-month follow-up. Length of hospital stay was reduced significantly by 87%, with notable improvements in patients’ functioning (17%) and symptomatology (14.5%).

Conclusions:

This study highlights the efficacy of a hybrid Assertive Community Treatment model in rural Greece for patients with severe mental illness, demonstrating significant reductions in hospitalizations and length of stay and improvements in symptomatology and functioning, suggesting its potential to address the needs of difficult-to-engage SMI patients and enhance their overall outcomes.

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Aspergillosis in the course of childhood acute lymphoblastic leukaemia: an unexpected enemy

Acute lymphoblastic leukemia (ALL) is a malignant lymphoid tumor, most common in children aged 1-4. Well-diagnosed and treated ALL allows for a 5-year survival rate of up to 90% in pediatric patients.

A girl aged 3 years and 6 months was referred to the Department of Paediatric Haematology, Oncology and Transplantology of the University Children's Hospital in Lublin with suspected proliferative haematopoietic disease.

Laboratory tests revealed leucopenia, neutropenia and significant anaemia. Bone marrow aspiration biopsy showed a hypocellular marrow with 23.6% young blastic cells. Flow cytometry showed 42% B lymphocyte precursor cells. The patient's morphology results steadily improved, and a subsequent biopsy showed the absence of atypical cells. Despite the improvement in morphology results, a month later, 90% of atypical cells were found and a biopsy confirmed pre-B acute lymphoblastic leukaemia. Chemotherapy according to the IA Protocol of the ALLIC-BFM Programme 2009 was started.

From the 18th day of treatment, the patient's condition worsened; she started to have a fever, and her inflammatory parameters were increasing. Broad-spectrum antibiotic therapy was ineffective. Chest CT scan revealed massive inflammatory densities in the left lung. Antifungal drugs (v-fend) were included. The girl's condition continued to deteriorate; a seizure occurred and head CT showed hypodense foci in the parietal lobes. After 5 days, in the area of the skull, a protrusion of the skin occurred, and diagnostic tests confirmed the presence of mycelial strands of Aspergillus (Aspergillosis) in the liquefied brain tissue, necessitating neurosurgical evacuation of the necrotic lesions. Intensive antifungal treatment was continued.

Five months later, resection of the lower lobe of the left lung was performed. After 1.5 years, there was a recurrence of the proliferative process, without reactivation of invasive mycosis.

Regular monitoring and treatment of complications are crucial for the long-term survival of patients.

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Elucidating the Intricacies of Cytokine Release Syndrome (CRS) in Hematological Malignancies and the Associated Risk Factors: A National Study
, , , , , ,

Hematologic malignancies carry a heightened risk of Cytokine Release Syndrome (CRS) due to cytotoxic chemotherapies and Chimeric Antigen Receptor T (CAR-T) cellular therapies. This study explores the relationship between various risk factors and CRS in patients with hematological malignancies.

Utilizing National Inpatient Sample (NIS) data from 2019 and 2020, we identified patients with hematological malignancies and a secondary diagnosis of CRS. We examined mortality, length of stay, and total treatment costs, conducting a multivariate regression analysis to assess the association of different risk factors with CRS.

A total of 200,590 patients were hospitalized with hematological malignancies, of whom 340 developed CRS. No statistically significant differences were observed in baseline demographic characteristics such as age, sex, insurance and income status, race, hospital teaching, rural, and size status. However, the odds of mortality were increased in CRS patients (OR 3.32, 95% CI 2.93-3.76, P<0.001). Total charges were significantly increased in CRS patients (+USD 654,286, 95% CI 375,835-932,636, P<0.001), but no difference was noted in length of stay between the two groups (+3.13, 95% CI 0.38-5.88, P=0.025). Fluid and electrolyte disorders (OR 2.71, 95% CI 2.47-2.97, P<0.001), obesity (OR 1.15, 95% CI 1.01-1.32, P=0.027), and heart failure (OR 1.39, 95% CI 1.2-1.6, P<0.001) demonstrated a higher risk of association with CRS. CRS patients were also more likely to have palliative care involvement (OR 1.71, 95% CI 1.52-1.92, P<0.001). Conversely, hypertension (OR 0.84, 95% CI 0.76-0.93, P=0.001) and major depressive disorder (OR 0.74, 95% CI 0.64-0.86, P<0.001) were associated with a decreased risk of CRS in hematological cancer patients.

CRS in hematological cancer patients is linked to increased mortality and hospitalization costs. Key risk factors include obesity, heart failure, and fluid and electrolyte disorders. Emphasizing holistic management of these conditions and adhering to evidence-based practices is crucial for improving patient outcomes and reducing adverse events.

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