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1.
Sci Adv ; 10(23): eadj4735, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38838150

RESUMEN

Why individuals with Down syndrome (DS) are more susceptible to SARS-CoV-2-induced neuropathology remains elusive. Choroid plexus (ChP) plays critical roles in barrier function and immune response modulation and expresses the ACE2 receptor and the chromosome 21-encoded TMPRSS2 protease, suggesting its substantial role in establishing SARS-CoV-2 infection in the brain. To explore this, we established brain organoids from DS and isogenic euploid iPSC that consist of a core of functional cortical neurons surrounded by a functional ChP-like epithelium (ChPCOs). DS-ChPCOs recapitulated abnormal DS cortical development and revealed defects in ciliogenesis and epithelial cell polarity in ChP-like epithelium. We then demonstrated that the ChP-like epithelium facilitates infection and replication of SARS-CoV-2 in cortical neurons and that this is increased in DS. Inhibiting TMPRSS2 and furin activity reduced viral replication in DS-ChPCOs to euploid levels. This model enables dissection of the role of ChP in neurotropic virus infection and euploid forebrain development and permits screening of therapeutics for SARS-CoV-2-induced neuropathogenesis.


Asunto(s)
Encéfalo , COVID-19 , Plexo Coroideo , Síndrome de Down , Organoides , SARS-CoV-2 , Serina Endopeptidasas , Plexo Coroideo/virología , Plexo Coroideo/metabolismo , Plexo Coroideo/patología , Organoides/virología , Organoides/metabolismo , Organoides/patología , Humanos , SARS-CoV-2/fisiología , COVID-19/virología , COVID-19/patología , COVID-19/metabolismo , Serina Endopeptidasas/metabolismo , Serina Endopeptidasas/genética , Síndrome de Down/metabolismo , Síndrome de Down/patología , Síndrome de Down/genética , Encéfalo/virología , Encéfalo/patología , Encéfalo/metabolismo , Neuronas/metabolismo , Neuronas/virología , Neuronas/patología , Replicación Viral , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/virología , Furina/metabolismo , Furina/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/genética , Tropismo Viral
2.
PLoS Pathog ; 20(6): e1011883, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38838057

RESUMEN

ATP-binding cassette (ABC) transport systems are crucial for bacteria to ensure sufficient uptake of nutrients that are not produced de novo or improve the energy balance. The cell surface of the pathobiont Streptococcus pneumoniae (pneumococcus) is decorated with a substantial array of ABC transporters, critically influencing nasopharyngeal colonization and invasive infections. Given the auxotrophic nature of pneumococci for certain amino acids, the Ami ABC transporter system, orchestrating oligopeptide uptake, becomes indispensable in host compartments lacking amino acids. The system comprises five exposed Oligopeptide Binding Proteins (OBPs) and four proteins building the ABC transporter channel. Here, we present a structural analysis of all the OBPs in this system. Multiple crystallographic structures, capturing both open and closed conformations along with complexes involving chemically synthesized peptides, have been solved at high resolution providing insights into the molecular basis of their diverse peptide specificities. Mass spectrometry analysis of oligopeptides demonstrates the unexpected remarkable promiscuity of some of these proteins when expressed in Escherichia coli, displaying affinity for a wide range of peptides. Finally, a model is proposed for the complete Ami transport system in complex with its various OBPs. We further disclosed, through in silico modelling, some essential structural changes facilitating oligopeptide transport into the cellular cytoplasm. Thus, the structural analysis of the Ami system provides valuable insights into the mechanism and specificity of oligopeptide binding by the different OBPs, shedding light on the intricacies of the uptake mechanism and the in vivo implications for this human pathogen.

3.
J Obstet Gynaecol ; 44(1): 2349965, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38727718

RESUMEN

BACKGROUND: Lichen sclerosus (LS) is a chronic, inflammatory disease of the genital and extra genital skin, causing pruritus, soreness, pain and dyspareunia. The aim of this study was to investigate whether Low Level Laser Therapy (LLLT) can improve the quality of life in women with Lichen sclerosus (LS) and insufficient topical treatment. METHODS: In a descriptive prospective observational study conducted between 02.01.2016 and 08.01.2018, we included 100 women with LS with insufficient topical treatment because of poor response of symptoms. All participants received ten LLLT treatments (808 nm and 500 mW) over a period of 8 weeks. The first four treatments were planned as two treatments per week. The remaining six treatments were planned as once a week. A Danish health-related quality of life tool (HRQoL test) monitored the effect. RESULTS: A total of 94 patients completed the study, median age of 62 [InterQuartile Range 53-69]. There was a statistically significant improvement in seven of the eight domains of the HRQoL test after ten LLLT. We found the results of DoloTest to be statistically significant in all of the groups except for smoking (p < 0.094). CONCLUSIONS: LLLT treatment can improve the quality of life in women with LS.


Lichen sclerosus is a chronic, inflammatory disease of the genital and extra genital skin, causing pruritus, soreness, pain and dyspareunia. This study aimed to investigate whether Low Level Laser Therapy can improve the quality of life in women with Lichen sclerosus and insufficient topical treatment. The study proposed a supplemental therapy to insufficient topical treatment in patients with Lichen sclerosus. This study indicated that Low Level Laser Therapy treatment can improve the quality of life in women with Lichen sclerosus.


Asunto(s)
Terapia por Luz de Baja Intensidad , Calidad de Vida , Liquen Escleroso Vulvar , Humanos , Femenino , Liquen Escleroso Vulvar/terapia , Liquen Escleroso Vulvar/radioterapia , Persona de Mediana Edad , Terapia por Luz de Baja Intensidad/métodos , Estudios Prospectivos , Anciano , Resultado del Tratamiento
4.
Chem Commun (Camb) ; 60(45): 5877, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38775135

RESUMEN

Correction for 'Facile preparation of a Ni-imidazole compound with high activity for ethylene dimerization' by Zhaohui Liu et al., Chem. Commun., 2024, 60, 188-191, https://doi.org/10.1039/D3CC04794F.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38644714

RESUMEN

INTRODUCTION: In this study, a series of novel piperazine derivatives were synthesised with high-to-good yields, and their structural analogies were confirmed using FTIR, 1H-NMR, and LC-MS techniques. METHOD: The synthesised compounds were evaluated for antioxidant and antimicrobial activities. Among the four synthesised piperazine derivatives, compound PD-2 exhibited relatively good antioxidant activity, with an IC50 value of 2.396 µg/mL, while the other three derivatives showed moderate to low antioxidant activity. Furthermore, compound PD-2 displayed antimicrobial activity against Pseudomonas aeruginosa, a gram-negative bacterium, and Candida albicans, a fungus. However, all four compounds showed strong resistance against grampositive bacteria, Staphylococcus aureus. RESULT: Additionally, compound PD-1 exhibited significant antihistamine activity, eliciting an 18.22% reduction in histamine levels. Both PD-1 and PD-2 demonstrated noteworthy anti-inflammatory activity in a dosedependent manner (5-10µM), leading to the inhibition of nitrite production up to 39.42% and 33.7% at higher concentrations (10 µM) and inhibition of tumour necrosis factor-alpha (TNF-α) generation up to 56.97% and 44.73% at 10 µM, respectively. Additionally, both novel molecules PD-1 and PD-2 effectively restrained the growth of HepG2 cells in a manner that is dependent on the dosage up to 55.44% and 90.45% at the highest concentrations (100 µg/mL), respectively. CONCLUSION: These findings substantiate the rationale for further investigation into the novel series of persuasive piperazine analogues as potential agents with anti-inflammatory, antihistamine and anticancer properties.

6.
Cureus ; 16(3): e57085, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38681262

RESUMEN

Rosacea is a common cutaneous condition caused by persistent, recurring lesions in facial skin vessels. It is a chronic skin condition with a variety of clinical symptoms and an unknown cause. Rosacea begins with the widening of capillaries and a flushed appearance. Following that, telangiectasia appears, and reddened patches persist, particularly on the cheeks and nose. Erythema persists due to repeated vasodilation and telangiectasia. In addition, skin inflammation manifests as papules, pustules, lymphedema, and fibrosis. Despite recent advances in treatment, rosacea, a chronic inflammatory relapsing central facial dermatosis, can be extremely difficult to manage.  The purpose of this meta-analysis and systematic review was to evaluate the effectiveness of low-dose isotretinoin in the treatment of rosacea. Following the guidelines set forth by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA), the researcher employed the following search terms in the EMBASE, Web of Science, PubMed, Cochrane Library, and Google Scholar databases to provide a therapeutic update relevant to clinical practice: "low dose isotretinoin," "isotretinoin and rosacea," "isotretinoin treatment of rosacea," and "effectiveness of isotretinoin in treating rosacea". The search was carried out by the researcher for articles published from February 2019 to February 2024. The articles included were all published in the English language. The overall frequency of patients with adverse events differed significantly between the groups treated with low-dose isotretinoin and the comparators (minocycline, pulsed dye laser, evening primrose oil, Lactobacillus plantarum, doxycycline, combined dose or placebo) (0.80, 95% CI 0.73 to 0.88, p = 0.0001). Sub-group analysis indicated that there was a difference between the interventions used in the treatments all in favor of low-dose isotretinoin treatment. The results showed that the moderate group had RR: 0.76, 95% CI: 0.44-1.30, I2 = 0%; the mild group had RR: 0.94, 95% CI: 0.56-1.57, I2 = 0%; and the group with severe rosacea had RR: 0.73, 95% CI: 0.47-1.13, I2 = 0%. According to this study, rosacea can be treated effectively with low-dose isotretinoin even in patients at severe stages of the disease by using the recommended dose once a week. Further, the intervention has also been shown to have fewer side effects on the patients. Therefore, this study recommends randomized controlled trials to be done to fully investigate the best combination options for isotretinoin on mild to severe rosacea based on the fact that some of the treatments combined have shown to be effective on treatment.

7.
Saudi Pharm J ; 32(5): 102049, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38571765

RESUMEN

Background: Patients with sickle cell disease (SCD) have just one recognized curative therapy option: hematopoietic stem cell transplantation (HSCT), which results in a long-lasting improvement in the clinical phenotype. Here, we assessed the effectiveness of HSCT in treating children with SCD by a systematic review and meta-analysis. Methods: Up until January 2024, a comprehensive search was done using Web of Science, CINAHL, Embase, Google Scholar, Cochrane Library, PubMed/Medline, and Embase. Two reviewers worked separately to extract the data, and Newcastle-Ottawa Quality Assessment tool was used to assess the research's quality. The outcomes analyzed were Overall survival (OS), event-free survival (EFS), graft failure (GF) and mortality. Results: Nineteen papers satisfied our inclusion requirements and were assessed to be of fair quality. The pooled rate of OS was high (92%; 95% CI: 90.3%-93.5%). Similar finding was detected for EFS (85.8%; 95% CI: 83.7%-87.7%). In the other hand, pooled rates of GF and mortality were 6.9% (95% CI: 5.3%-8.9%) and 7.4% (95% CI: 5%-10.7%), respectively. A significant publication bias was detected for OS, EFS and GF outcomes. Subgroups analysis showed that study design was the major source of heterogeneity. Conclusion: Our results show that HSCT is effective and safe, with pooled survival rates above 90%. It is important to assess innovative tactics in light of the alarming GF and mortality rates.

8.
Nat Commun ; 15(1): 2231, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38472184

RESUMEN

Detecting and responding to threat engages several neural nodes including the amygdala, hippocampus, insular cortex, and medial prefrontal cortices. Recent propositions call for the integration of more distributed neural nodes that process sensory and cognitive facets related to threat. Integrative, sensitive, and reproducible distributed neural decoders for the detection and response to threat and safety have yet to be established. We combine functional MRI data across varying threat conditioning and negative affect paradigms from 1465 participants with multivariate pattern analysis to investigate distributed neural representations of threat and safety. The trained decoders sensitively and specifically distinguish between threat and safety cues across multiple datasets. We further show that many neural nodes dynamically shift representations between threat and safety. Our results establish reproducible decoders that integrate neural circuits, merging the well-characterized 'threat circuit' with sensory and cognitive nodes, discriminating threat from safety regardless of experimental designs or data acquisition parameters.


Asunto(s)
Encéfalo , Miedo , Humanos , Miedo/fisiología , Amígdala del Cerebelo , Mapeo Encefálico , Señales (Psicología) , Imagen por Resonancia Magnética , Corteza Prefrontal/fisiología
9.
Int J Stem Cells ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38531607

RESUMEN

Stem cells and the cells they produce are unique because they vary from one cell to another. Traditional methods of studying cells often overlook these differences. However, the development of new technologies for studying individual cells has greatly changed biological research in recent years. Among these innovations, single-cell RNA sequencing (scRNA-seq) stands out. This technique allows scientists to examine the activity of genes in each cell, across thousands or even millions of cells. This makes it possible to understand the diversity of cells, identify new types of cells, and see how cells differ across different tissues, individuals, species, times, and conditions. This paper discusses the importance of scRNA-seq and the computational tools and software that are essential for analyzing the vast amounts of data generated by scRNA-seq studies. Our goal is to provide practical advice for bioinformaticians and biologists who are using scRNA-seq to study stem cells. We offer an overview of the scRNA-seq field, including the tools available, how they can be used, and how to present the results of these studies effectively. Our findings include a detailed overview and classification of tools used in scRNA-seq analysis, based on a review of 2,733 scientific publications. This review is complemented by information from the scRNA-tools database, which lists over 1,400 tools for analyzing scRNA-seq data. This database is an invaluable resource for researchers, offering a wide range of options for analyzing their scRNA-seq data.

10.
Cureus ; 16(1): e52413, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38370991

RESUMEN

INTRODUCTION: Parents' ability to engage and raise their children in a safe and appropriate manner is largely influenced by their knowledge of child development and childrearing. This study aimed to evaluate the parenting and developmental milestone (MS) knowledge of Western region Saudi parents and identify the related elements that influence their knowledge. METHODS: This cross­sectional study was conducted for a period of six months. Ethical approval was duly sanctioned by the Institutional Review Board (IRB), and prior to participation, written informed consent was diligently procured from all the individuals involved in the study. In adherence to the paramount principles of privacy, rigorous measures were employed to de­identify the personal data of the participants, thereby safeguarding their confidentiality and anonymity. All research procedures were meticulously executed in strict compliance with the pertinent guidelines and regulatory standards governing research ethics. The study cohort consisted of Saudi parents from the Western Province of Saudi Arabia who had children aged up to six years and expressed a genuine willingness to participate in the research. This commitment was reaffirmed through their informed consent. Notably, the inclusion criteria for parental involvement did not impose any restrictions based on age or ethnic origin, ensuring a diverse and inclusive representation of this crucial demographic group. RESULTS: For assessing parental awareness and knowledge about children's developmental MSs, we examined a diverse sample of 873 participants, predominantly comprising females (77.00%). The age distribution revealed that a substantial portion of the respondents were below 30 (37.00%). Most respondents (62.40%) sought information from medical physicians and pediatricians. Gender had a significant effect, with males showing a lower awareness level compared to females (Beta = -0.582, 95% confidence interval (CI) [-0.890, -0.274], p-value < 0.001). Marital status demonstrated significance, where divorced individuals showed a lower awareness level than widowed participants (Beta = -1.641, 95% CI [-2.993, -0.288], p-value = 0.017). At the same time, no significant differences were found for singles or married individuals. CONCLUSION: Saudi parents lacked understanding of other parenting skills, such as a baby's personality and temperament, but they were well educated about some areas of childrearing, primarily physical safety precautions. It is advised that nurses and doctors give parenting advice to families at every step of their children's growth to educate and support them.

11.
J Cardiothorac Vasc Anesth ; 38(5): 1088-1091, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38423885

RESUMEN

The Pediatric Cardiac Anesthesia (PCA) fellowship is a demanding training program in Europe and the United States. Successful completion of the program requires years of training in anesthesiology, a thorough understanding of cardiovascular anatomy and physiology, and extensive experience in the perioperative management of neonates and children with heart disease. In the context of the first candidate to successfully complete the PCA program in Europe, this article presents excerpts from the design and structure of the European PCA program. The PCA program is evaluated critically by both external and internal reviewers, and points are highlighted that could be included in the next version of the program.


Asunto(s)
Anestesia en Procedimientos Quirúrgicos Cardíacos , Anestesiología , Recién Nacido , Humanos , Niño , Estados Unidos , Becas , Anestesiología/educación , Educación de Postgrado en Medicina , Anestesia Pediátrica
12.
ACS Appl Mater Interfaces ; 16(5): 5598-5612, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38270979

RESUMEN

Imaging plays a critical role in all stages of cancer care from early detection to diagnosis, prognosis, and therapy monitoring. Recently, photoacoustic imaging (PAI) has started to emerge into the clinical realm due to its high sensitivity and ability to penetrate tissues up to several centimeters deep. Herein, we encapsulated indocyanine green J (ICGJ) aggregate, one of the only FDA-approved organic exogenous contrast agents that absorbs in the near-infrared range, at high loadings up to ∼40% w/w within biodegradable polymersomes (ICGJ-Ps) composed of poly(lactide-co-glycolide-b-polyethylene glycol) (PLGA-b-PEG). The small Ps hydrodynamic diameter of 80 nm is advantageous for in vivo applications, while directional conjugation with epidermal growth factor receptor (EGFR) targeting cetuximab antibodies renders molecular specificity. Even when exposed to serum, the ∼11 nm-thick membrane of the Ps prevents dissociation of the encapsulated ICGJ for at least 48 h with a high ratio of ICGJ to monomeric ICG absorbances (i.e., I895/I780 ratio) of approximately 5.0 that enables generation of a strong NIR photoacoustic (PA) signal. The PA signal of polymersome-labeled breast cancer cells is proportional to the level of cellular EGFR expression, indicating the feasibility of molecular PAI with antibody-conjugated ICGJ-Ps. Furthermore, the labeled cells were successfully detected with PAI in highly turbid tissue-mimicking phantoms up to a depth of 5 mm with the PA signal proportional to the amount of cells. These data show the potential of molecular PAI with ICGJ-Ps for clinical applications such as tumor margin detection, evaluation of lymph nodes for the presence of micrometastasis, and laparoscopic imaging procedures.


Asunto(s)
Inmunoconjugados , Técnicas Fotoacústicas , Verde de Indocianina/química , Medios de Contraste/química , Análisis Espectral , Imagen Molecular , Receptores ErbB , Técnicas Fotoacústicas/métodos
13.
Int J Pharm X ; 7: 100227, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38260917

RESUMEN

Diabetes mellitus is a metabolic disease that raises the odds of developing stroke. Candesartan has been used to prevent stroke due to its inhibitory effects on blood pressure, angiogenesis, oxidative damage, and apoptosis. However, oral candesartan has very limited bioavailability and efficacy due to its weak solubility and slow release. The study aimed to develop a nasal formulation of candesartan-loaded liposomes containing ethanol and propylene glycol (CLEP) to improve candesartan's delivery, release, permeation, and efficacy as a potential diabetes-associated stroke treatment. Using design expert software, different CLEP formulations were prepared and evaluated in vitro to identify the optimum formulation, which. The selected optimum formulation composed of 3.3% phospholipid, 10% ethanol, and 15% propylene glycol significantly increased the release and permeation of candesartan relative to free candesartan by a factor of 1.52 and 1.47, respectively. The optimum formulation significantly reduced the infarction after stroke in rats; decreased flexion, spontaneous motor activity, and time spent in the target quadrant by 70%, 64.71%, and 92.31%, respectively, and enhanced grip strength by a ratio of 2.3. Therefore, nasal administration of the CLEP formulation could be a potential diabetes-associated stroke treatment.

14.
Cureus ; 16(1): e52523, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38239845

RESUMEN

Nemaline myopathy is a primary skeletal muscle disorder and one of the congenital myopathies. It can be caused by mutations in at least 12 genes, with the nebulin (NEB) gene being the most common. Here, we present the first case of a neonate with nemaline myopathy from Al-Qunfudhah, Saudi Arabia. A full-term baby boy was delivered via cesarean section due to decreased fetal movement. The baby was covered with a thick meconium stain. He was born with severe distress and underwent an endotracheal tube placement. The baby presented generalized muscle weakness, hypotonia, and areflexia. Examination revealed arthrogryposis, bilateral small chin, undescended testicle, joint deformity, hip dislocation, and clubfoot. Chest examination revealed conducting sound and bilateral equal air entry. Moreover, he experienced bilateral chest wheeze and conducting sound. All laboratory tests were normal, and whole-exome sequencing revealed pathogenic homozygous splice acceptor variant NEB gene c.8889+1G˃A. The patient was first suspected to have spinal muscular atrophy as there was no previous nemaline myopathy case reported from Al-Qunfudhah. However, the typical symptoms and genetic sequencing confirmed his condition. As the society in Al-Qunfudhah is known for consanguinity, as in our case, clinicians should identify other types of myopathy as it is expected to occur in further cases.

16.
Psychol Med ; 54(4): 835-846, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37655520

RESUMEN

BACKGROUND: The ability to extinguish a maladaptive conditioned fear response is crucial for healthy emotional processing and resiliency to aversive experiences. Therefore, enhancing fear extinction learning has immense potential emotional and health benefits. Mindfulness training enhances both fear conditioning and recall of extinguished fear; however, its effects on fear extinction learning are unknown. Here we investigated the impact of mindfulness training on brain mechanisms associated with fear-extinction learning, compared to an exercise-based program. METHODS: We investigated BOLD activations in response to a previously learned fear-inducing cue during an extinction paradigm, before and after an 8-week mindfulness-based stress reduction program (MBSR, n = 49) or exercise-based stress management education program (n = 27). RESULTS: The groups exhibited similar reductions in stress, but the MBSR group was uniquely associated with enhanced activation of salience network nodes and increased hippocampal engagement. CONCLUSIONS: Our results suggest that mindfulness training increases attention to anticipatory aversive stimuli, which in turn facilitates decreased aversive subjective responses and enhanced reappraisal of the memory.


Asunto(s)
Miedo , Atención Plena , Humanos , Miedo/fisiología , Extinción Psicológica/fisiología , Encéfalo , Recuerdo Mental/fisiología , Imagen por Resonancia Magnética
17.
Drug Deliv Transl Res ; 14(2): 474-490, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37605039

RESUMEN

Atherosclerosis is an inflammatory disease characterized by the accumulation of arterial plaque. Diabetes mellitus stands out as a major risk factor for atherosclerosis. Candesartan is a potent angiotensin II receptor antagonist that enhances arterial blood flow and reduces insulin resistance. However, oral candesartan has limited activity because of its low bioavailability, water solubility, hepatic first-pass degradation, and efficacy. The current study aims to develop nasal candesartan-loaded invasome (CLI) drops to improve candesartan's permeation, release, and bioavailability as a potential treatment for diabetes-associated atherosclerosis. Design expert software was used to prepare various CLI formulations to determine the impact of the concentrations of ethanol, cineole, and phospholipid. The desirability index was used to estimate the optimized formulation composition to maximize entrapment efficiency and minimize vesicle size. The optimized formulation had a 1% ethanol concentration, a 1.5% cineole concentration, and a 2.32% phospholipid concentration. The selected optimized formulation was then tested in a rat model of diabetes and atherosclerosis to evaluate its activity. The results showed that nasal CLI drops significantly raised serum HDL levels by a ratio of 1.42 and lowered serum glucose, cholesterol, triglycerides, LDL, and VLDL levels by 69.70%, 72.22%, 36.52%, 58.0%, and 65.31%, respectively, compared with diabetic atherosclerotic rats, throwing an insight on the potential for promising anti-diabetic and anti-atherosclerotic activities. Additionally, atherosclerotic lesions were improved in rats treated with CLI, as shown in histopathology. In conclusion, the results of this investigation showed that treatment with nasal CSN-loaded invasome formulation drops prevented the initiation and progression of diabetes-associated atherosclerosis.


Asunto(s)
Aterosclerosis , Diabetes Mellitus , Ratas , Animales , Eucaliptol , Aterosclerosis/tratamiento farmacológico , Fosfolípidos , Etanol
18.
J Clin Oncol ; 42(1): 59-69, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37871266

RESUMEN

PURPOSE: Geriatric assessment (GA) is a guideline-recommended approach to optimize cancer management in older adults. We conducted a cost-utility analysis alongside the 5C randomized controlled trial to compare GA and management (GAM) plus usual care (UC) against UC alone in older adults with cancer. METHODS: The economic evaluation, conducted from societal and health care payer perspectives, used a 12-month time horizon. The Canadian 5C study randomly assigned patients to receive GAM or UC. Quality-adjusted life-years (QALYs) were measured using the EuroQol five dimension-5L questionnaire and health care utilization using cost diaries and chart reviews. We evaluated the incremental net monetary benefit (INMB) for the full sample and preselected subgroups. RESULTS: A total of 350 patients were included, of whom 173 received GAM and 177 UC. At 12 months, the average QALYs per patient were 0.728 and 0.751 for GAM and UC, respectively (ΔQALY, -0.023 [95% CI, -0.076 to 0.028]). Considering a societal perspective, the total average costs (in 2021 Canadian dollars) per patient were $46,739 and $45,177 for GAM and UC, respectively (ΔCost, $1,563 [95% CI, -$6,583 to $10,403]). At a cost-effectiveness threshold of $50,000/QALY, GAM was not cost-effective compared with UC (INMB, -$2,713 [95% CI, -$11,767 to $5,801]). The INMB was positive ($2,984 [95% CI, -$7,050 to $14,179]; probability of being cost-effective, 72%) for patients treated with curative intent, but remained negative for patients treated with palliative intent (INMB, -$9,909 [95% CI, -$24,436 to $4,153]). Findings were similar considering a health care payer perspective. CONCLUSION: To our knowledge, this is the first cost-utility analysis of GAM in cancer. GAM was cost-effective for patients with cancer treated with curative but not with palliative intent. The study provides further considerations for future adoption of GAM in practice.


Asunto(s)
Evaluación Geriátrica , Neoplasias , Anciano , Humanos , Canadá , Análisis Costo-Beneficio , Neoplasias/economía , Neoplasias/terapia , Aceptación de la Atención de Salud , Años de Vida Ajustados por Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto
19.
Chem Commun (Camb) ; 60(2): 188-191, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38044830

RESUMEN

A compound consisting of Ni and imidazole (Ni-imidazole) was synthesized in large quantities by a one-step co-precipitation method. The structure and stability of this Ni-imidazole were well studied by a series of characterization methods. The Ni-imidazole compound exhibited excellent catalytic properties for the dimerization of ethylene to 1-butene.

20.
ACS Omega ; 8(46): 44112-44120, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-38027317

RESUMEN

Heat loss is a major challenge in heat transfer problems. Several researchers have minimized heat loss for different heat transfer cases, focusing on one optimization technique; however, not all optimization techniques are suitable for a given problem. A limited number of studies have compared different techniques for a given problem under boundary conditions and constraints. This review revisits basic heat transfer problems and identifies a promising technique for each problem to minimize heat loss. The paper considers three techniques: nonlinear least-squares error (LSE), interior point linear programming (IPLP), and genetic algorithm. Two cases are studied: 1. heat loss optimization from cylindrical insulating surfaces and 2. laminar airflow on a heated plate. The results are compared for each technique, and a suitable technique is recommended for each considered case. Nonlinear LSE is found to be most suitable for case 1. IPLP and GA are recommended for the Case 2 problem. The average thermal conductivity is found to be 0.081 W/mK. The average insulation thickness is found to be 213.25 mm. This research will act as a basis for future research to justify and implement suitable techniques for different heat transfer problems.

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