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OBJECTIVE: The increasing concern over adolescent suicide necessitates suicide prevention training for school teachers, as students spend a significant portion of their time at school. This study's objective is to develop a suicide prevention program tailored for teachers. METHODS: The program was developed by a multidisciplinary research team, drawing on a review of both domestic and international suicide prevention programs, related scholarly articles, and Korean psychological autopsy interviews of adolescents. This was complemented by a survey of teachers to assess the program's practicality and usability. RESULTS: The developed program comprises three parts, consistent with other versions: Careful Observation, Active Listening, and Risk Evaluation and Expert Referral. Careful Observation focuses on training teachers to recognize verbal, behavioral, and situational warning signs of suicidal ideation in students; Active Listening involves strategies for encouraging students to express their suicidal thoughts and techniques for being an empathetic and attentive listener; Risk Evaluation and Expert Referral provides instruction on how to assess suicide risk and assist students safely. CONCLUSION: It is anticipated that this program will equip teachers with valuable knowledge and skills, contributing to a reduction in adolescents suicide rates.
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Due to the severe climate crisis, biorefineries have been highlighted as replacements for fossil fuel-derived refineries. In traditional sugar-based biorefineries, levulinic acid (LA) is a byproduct. Nonetheless, in 2002, the US Department of Energy noted that LA is a significant building block obtained from biomass, and the biorefinery paradigm has shifted from being sugar-based to non-sugar-based. Accordingly, LA is of interest in this review since it can be converted into useful precursors and ultimately can broaden the product spectrum toward more valuable products (e.g., fuels, plastics, and pharmaceuticals), thereby enabling the construction of economically viable biorefineries. This study comprehensively reviews LA production techniques utilizing various bioresources. Recent progress in enzymatic and microbial routes for LA valorization and the LA-derived product spectrum and its versatility are discussed. Finally, challenges and future outlooks for LA-based non-sugar biorefineries are suggested.
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The emergence of multidrug-resistant bacteria poses a significant threat to human health, necessitating a comprehensive understanding of their underlying mechanisms. Uropathogenic Escherichia coli (UPEC), the primary causative agent of urinary tract infections, is frequently associated with multidrug resistance and recurrent infections. To elucidate the mechanism of resistance of UPEC to beta-lactam antibiotics, we generated ampicillin-resistant UPEC strains through continuous exposure to low and high levels of ampicillin in the laboratory, referred to as Low AmpR and High AmpR, respectively. Whole-genome sequencing revealed that both Low and High AmpR strains contained mutations in the marR, acrR, and envZ genes. The High AmpR strain exhibited a single additional mutation in the nlpD gene. Using protein modeling and qRT-PCR analyses, we validated the contributions of each mutation in the identified genes to antibiotic resistance in the AmpR strains, including a decrease in membrane permeability, increased expression of multidrug efflux pump, and inhibition of cell lysis. Furthermore, the AmpR strain does not decrease the bacterial burden in the mouse bladder even after continuous antibiotic treatment in vivo, implicating the increasing difficulty in treating host infections caused by the AmpR strain. Interestingly, ampicillin-induced mutations also result in multidrug resistance in UPEC, suggesting a common mechanism by which bacteria acquire cross-resistance to other classes of antibiotics.
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Ampicilina , Antibacterianos , Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli , Mutação , Infecções Urinárias , Escherichia coli Uropatogênica , Escherichia coli Uropatogênica/genética , Escherichia coli Uropatogênica/efeitos dos fármacos , Animais , Farmacorresistência Bacteriana Múltipla/genética , Infecções Urinárias/microbiologia , Infecções por Escherichia coli/microbiologia , Camundongos , Antibacterianos/farmacologia , Ampicilina/farmacologia , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Feminino , Humanos , Testes de Sensibilidade Microbiana , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Suicide is a serious social problem among older adults. However, little is known about how multidimensional factors affect suicide of older adults. AIMS: We classify the multidimensional suicidal risk types of older adults based on their characteristics and identify differences in suicidal ideation. METHOD: Data were obtained via a nationwide online survey targeting 612 older adults over the age of 55 years. A latent profile analysis identified three profiles, one of which represented the optimal situation for these adults. RESULTS: We identified three distinct multidimensional suicidal risk types in older adults: high-risk predicament (24.5%), moderate-risk predicament (57.7%) and abundant internal/external resources (17.8%). In particular, depression, a major risk factor for suicide, was found together with self-neglect in each group. Multiple regression analysis showed that older adults in the moderate-risk predicament and high-risk predicament groups were more likely to have suicidal ideation than those in the abundant internal/external resources group. CONCLUSIONS: Our findings suggest that co-occurrence of depression and self-neglect represents a suicide risk pattern in high-risk older individuals. Therefore, local communities need to urgently screen and provide interventions for such older adults and strengthen their capacity for multidimensional aspects of life to prevent suicide in the long term.
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BACKGROUND: Histone H3K4 tri-methylation (H3K4me3) catalyzed by Set1/COMPASS, is a prominent epigenetic mark found in promoter-proximal regions of actively transcribed genes. H3K4me3 relies on prior monoubiquitination at the histone H2B (H2Bub) by Rad6 and Bre1. Swd2/Cps35, a Set1/COMPASS component, has been proposed as a key player in facilitating H2Bub-dependent H3K4me3. However, a more comprehensive investigation regarding the relationship among Rad6, Swd2, and Set1 is required to further understand the mechanisms and functions of the H3K4 methylation. RESULTS: We investigated the genome-wide occupancy patterns of Rad6, Swd2, and Set1 under various genetic conditions, aiming to clarify the roles of Set1 and Rad6 for occupancy of Swd2. Swd2 peaks appear on both the 5' region and 3' region of genes, which are overlapped with its tightly bound two complexes, Set1 and cleavage and polyadenylation factor (CPF), respectively. In the absence of Rad6/H2Bub, Set1 predominantly localized to the 5' region of genes, while Swd2 lost all the chromatin binding. However, in the absence of Set1, Swd2 occupancy near the 5' region was impaired and rather increased in the 3' region. CONCLUSIONS: This study highlights that the catalytic activity of Rad6 is essential for all the ways of Swd2's binding to the transcribed genes and Set1 redistributes the Swd2 to the 5' region for accomplishments of H3K4me3 in the genome-wide level.
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Histona-Lisina N-Metiltransferase , Histonas , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Histonas/metabolismo , Histonas/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Metilação , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/genéticaRESUMO
In liver transplantation, the primary concern is to ensure an adequate future liver remnant (FLR) volume for the donor, while selecting a graft of sufficient size for the recipient. The living donor-resection and partial liver segment 2-3 transplantation with delayed total hepatectomy (LD-RAPID) procedure offers a potential solution to expand the donor pool for living donor liver transplantation (LDLT). We report the first case involving a cirrhotic patient with autoimmune hepatitis and hepatocellular carcinoma, who underwent left lobe LDLT using the LD-RAPID procedure. The living liver donor (LLD) underwent a laparoscopic left hepatectomy, including middle hepatic vein. The resection on the recipient side was an extended left hepatectomy, including the middle hepatic vein orifice and caudate lobe. At postoperative day 7, a computed tomography scan showed hypertrophy of the left graft from 320 g to 465 mL (i.e., a 45.3% increase in graft volume body weight ratio from 0.60% to 0.77%). After a 7-day interval, the diseased right lobe was removed in the second stage surgery. The LD-RAPID procedure using left lobe graft allows for the use of a small liver graft or small FLR volume in LLD in LDLT, which expands the donor pool to minimize the risk to LLD by enabling the donation of a smaller liver portion.
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The Senior Meaning in Life Evaluation scale encompasses not only older adults' personal motivation and growth but also the meaning for them in society and in their relationships: With this scale, we aimed to present their voices. A three-phase process was followed: The scale's items were developed empirically from interviews of older adults; exploratory factor analysis (EFA) was conducted to test convergent and concurrent validity; and finally, confirmatory factor analysis (CFA) was performed. EFA resulted in 18 items grouped into 4 factors (i.e., proactive on life, overcoming emptiness, acceptance in life, and social contribution), which was supported by the CFA.
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Inquéritos e Questionários , Humanos , Idoso , Análise Fatorial , Psicometria/métodos , Reprodutibilidade dos TestesRESUMO
The contents and dynamics of spontaneous thought are important factors for personality traits and mental health. However, assessing spontaneous thoughts is challenging due to their unconstrained nature, and directing participants' attention to report their thoughts may fundamentally alter them. Here, we aimed to decode two key content dimensions of spontaneous thought-self-relevance and valence-directly from brain activity. To train functional MRI-based predictive models, we used individually generated personal stories as stimuli in a story-reading task to mimic narrative-like spontaneous thoughts (n = 49). We then tested these models on multiple test datasets (total n = 199). The default mode, ventral attention, and frontoparietal networks played key roles in the predictions, with the anterior insula and midcingulate cortex contributing to self-relevance prediction and the left temporoparietal junction and dorsomedial prefrontal cortex contributing to valence prediction. Overall, this study presents brain models of internal thoughts and emotions, highlighting the potential for the brain decoding of spontaneous thought.
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Mapeamento Encefálico , Encéfalo , Humanos , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Emoções , Córtex Pré-Frontal , Giro do Cíngulo , Imageamento por Ressonância Magnética/métodosRESUMO
Recent advances in regenerative medicine and tissue engineering have enabled the biofabrication of three-dimensional (3D) tissue analogues with the potential for use in transplants and disease modeling. However, the practical use of these biomimetic tissues has been hindered by the challenge posed by reconstructing anatomical-scale micro-vasculature tissues. In this study, we suggest that co-cultured spheroids within hydrogels hold promise for regenerating highly vascularized and innervated tissues, bothin vitroandin vivo. Human adipose-derived stem cells (hADSCs) and human umbilical vein cells (HUVECs) were prepared as spheroids, which were encapsulated in gelatin methacryloyl hydrogels to fabricate a 3D pre-vascularized tissue. The vasculogenic responses, extracellular matrix production, and remodeling depending on parameters like co-culture ratio, hydrogel strength, and pre-vascularization time forin vivointegration with native vessels were then delicately characterized. The co-cultured spheroids with 3:1 ratio (hADSCs/HUVECs) within the hydrogel and with a pliable storage modulus showed the greatest vasculogenic potential, and ultimately formedin vitroarteriole-scale vasculature with a longitudinal lumen structure and a complex vascular network after long-term culturing. Importantly, the pre-vascularized tissue also showed anastomotic vascular integration with host blood vessels after transplantation, and successful vascularization that was positive for both CD31 and alpha-smooth muscle actin covering 18.6 ± 3.6µm2of the luminal area. The described co-cultured spheroids-laden hydrogel can therefore serve as effective platform for engineering 3D vascularized complex tissues.
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Hidrogéis , Engenharia Tecidual , Humanos , Engenharia Tecidual/métodos , Hidrogéis/química , Técnicas de Cocultura , Células Endoteliais da Veia Umbilical Humana , Medicina Regenerativa , Alicerces Teciduais/químicaRESUMO
There is growing evidence that neonatal porcine islet-like cell clusters (NPCCs) isolated from piglets can be used to treat type 1 diabetes in humans. However, graft rejection is a common complication in humans owing to the prevalence of xenoantigens in porcine. Therefore, researchers have investigated various islet encapsulation techniques that could protect against these antigens. To this end, this study presents a robust nano-encapsulation method based on bifunctional polymersomes (PSomes), in which N-hydroxysuccinimide (NHS) and maleimide (Mal) groups conjugated to the PSomes terminal interact with the amine and thiol groups on the surface of NPCCs to induce dual targeting via two covalent bonds. The findings indicate that the ratio of NHS to Mal on PSomes is optimal for dual targeting. Moreover, triiodothyronine (T3) is known to promotes pancreatic islet maturation and differentiation of endocrine cells into beta cells. T3 encapsulated in PSomes is shown to increase the glucose sensitivity of NPCCs and enhance insulin secretion from NPCCs. Furthermore, improvements in the nano-encapsulation efficiency and insulin-secreting capability of NPCCs through dual targeting via dual-Psomes are demonstrated. In conclusion, the proposed nano-encapsulation technique could pave the way for significant advances in islet nano-encapsulation and the imprevement of NPCC immaturity via T3 release.
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Clinical decision support systems (CDSSs) play a critical role in enhancing the efficiency of mental health care delivery and promoting patient engagement. Transdiagnostic approaches that utilize raw psychological and biological data enable personalized patient profiling and treatment. This study introduces a CDSS incorporating symptom profiling and drug recommendation for mental health care. Among the UK Biobank cohort, we analyzed 157,348 participants for symptom profiling and 14,358 participants with a drug prescription history for drug recommendation. Among the 1307 patients in the Samsung Medical Center cohort, 842 were eligible for analysis. Symptom profiling utilized demographic and questionnaire data, employing conventional clustering and community detection methods. Identified clusters were explored using diagnostic mapping, feature importance, and scoring. For drug recommendation, we employed cluster- and network-based approaches. The analysis identified nine clusters using k-means clustering and ten clusters with the Louvain method. Clusters were annotated for distinct features related to depression, anxiety, psychosis, drug addiction, and self-harm. For drug recommendation, drug prescription probabilities were retrieved for each cluster. A recommended list of drugs, including antidepressants, antipsychotics, mood stabilizers, and sedative-hypnotics, was provided to individual patients. This CDSS holds promise for efficient personalized mental health care and requires further validation and refinement with larger datasets, serving as a valuable tool for mental healthcare providers.
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Bancos de Espécimes Biológicos , Biobanco do Reino Unido , Humanos , Preparações Farmacêuticas , Inquéritos e Questionários , Análise por Conglomerados , República da CoreiaRESUMO
This study aimed to determine the antimicrobial effectiveness of natural antimicrobial agents (NAAs) (yuzu juice, wasabi extract, and rosemary extract) against three target microorganisms (TMs) (Escherichia coli, Staphylococcus aureus, and Salmonella Typhimurium) and to determine the optimal concentration of these agents using response surface methodology (RSM) to ensure the safety of meal kits manufactured using marinade sauce. The three NAAs added to marinade sauce effectively inactivated TMs (P<0.05), in particular, yuzu juice had the greatest antimicrobial effect against TMs, followed by wasabi and rosemary extracts. To determine the optimal concentration of NAAs using RSM, 17 concentrations were tested with three TMs as dependent variables and three NAAs as independent variables. The results showed that E. coli was not present under any of the conditions tested, whereas S. aureus and S. Typhimurium exhibited different characteristics depending on the conditions. Through response surface analysis of the TMs except for E. coli, which was not detected, it was determined that S. aureus had a coefficient of determination (R2) of 0.928 and a lack of fit of 0.074, and the linear regression of [yuzu juice] (X1) and quadratic regression of [yuzu juice]2 (X12) were both significant (P<0.05). S. Typhimurium had an R2 of 0.8955 and a lack of fit of 0.051, and only the quadratic regression of [yuzu juice]2 (X12) was significant (P<0.05). Based on RSM and ridge analysis, the optimal mixed conditions were determined to be 3.92% (v/w) yuzu juice, 23.41% (v/w) wasabi extract, and 3.93% (v/w) rosemary extract. After investigating the antimicrobial effect under the optimal conditions, E. coli and S. Typhimurium were absent, and S. aureus was reduced to 2.50 ± 0.09 log colony-forming units/g after 24 h. The results indicated that mixed treatment with the three NAAs had a more significant antimicrobial effect due to their synergistic properties compared to when used in isolation.
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Anti-Infecciosos , Citrus , Microbiologia de Alimentos , Escherichia coli , Staphylococcus aureus , Extratos Vegetais/farmacologia , Antibacterianos , Contagem de Colônia MicrobianaRESUMO
Inorganic phosphate (Pi) is a fundamental molecule crucial for numerous biological processes, such as ATP synthesis and phospholipid formation. To prevent cellular toxicity, Pi transport is often linked to counterion transport within the bacterium. This review discusses the multifaceted functions of the PhoU protein in bacterial regulation, focusing on its role in coordinating Pi transport with counterions, controlling polyphosphate accumulation, and regulating secondary metabolite biosynthesis and DNA repair. We also explore recent findings that challenge the conventional view of PhoU simply as a negative regulator in phosphate signaling, suggesting its broader impact on bacterial physiology and stress response. Understanding the diverse functions of PhoU provides new insight into bacterial biology and offers potential therapeutic implications.
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Proteínas de Bactérias , Proteínas de Membrana Transportadoras , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Fatores de Transcrição/genética , Fosfatos/metabolismo , HomeostaseRESUMO
The endoplasmic reticulum (ER) is the largest intracellular organelle carrying out a broad range of important cellular functions including protein biosynthesis, folding, and trafficking, lipid and sterol biosynthesis, carbohydrate metabolism, and calcium storage and gated release. In addition, the ER makes close contact with multiple intracellular organelles such as mitochondria and the plasma membrane to actively regulate the biogenesis, remodeling, and function of these organelles. Therefore, maintaining a homeostatic and functional ER is critical for the survival and function of cells. This vital process is implemented through well-orchestrated signaling pathways of the unfolded protein response (UPR). The UPR is activated when misfolded or unfolded proteins accumulate in the ER, a condition known as ER stress, and functions to restore ER homeostasis thus promoting cell survival. However, prolonged activation or dysregulation of the UPR can lead to cell death and other detrimental events such as inflammation and oxidative stress; these processes are implicated in the pathogenesis of many human diseases including retinal disorders. In this review manuscript, we discuss the unique features of the ER and ER stress signaling in the retina and retinal neurons and describe recent advances in the research to uncover the role of ER stress signaling in neurodegenerative retinal diseases including age-related macular degeneration, inherited retinal degeneration, achromatopsia and cone diseases, and diabetic retinopathy. In some chapters, we highlight the complex interactions between the ER and other intracellular organelles focusing on mitochondria and illustrate how ER stress signaling regulates common cellular stress pathways such as autophagy. We also touch upon the integrated stress response in retinal degeneration and diabetic retinopathy. Finally, we provide an update on the current development of pharmacological agents targeting the UPR response and discuss some unresolved questions and knowledge gaps to be addressed by future research.
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Retinopatia Diabética , Degeneração Retiniana , Humanos , Degeneração Retiniana/metabolismo , Retinopatia Diabética/metabolismo , Resposta a Proteínas não Dobradas , Estresse do Retículo Endoplasmático/fisiologia , Retina , Retículo Endoplasmático/metabolismo , Homeostase/fisiologiaRESUMO
A combination of hydrogels and stem cell spheroids has been used to engineer three-dimensional (3D) osteochondral tissue, but precise zonal control directing cell fate within the hydrogel remains a challenge. In this study, we developed a composite spheroid-laden bilayer hydrogel to imitate osteochondral tissue by spatially controlled differentiation of human adipose-derived stem cells. Meticulous optimization of the spheroid-size and mechanical strength of gelatin methacryloyl (GelMA) hydrogel enables the cells to homogeneously sprout within the hydrogel. Moreover, fibers immobilizing transforming growth factor beta-1 (TGF-ß1) or bone morphogenetic protein-2 (BMP-2) were incorporated within the spheroids, which induced chondrogenic or osteogenic differentiation of cells in general media, respectively. The spheroids-filled GelMA solution was crosslinked to create the bilayer hydrogel, which demonstrated a strong interfacial adhesion between the two layers. The cell sprouting enhanced the adhesion of each hydrogel, demonstrated by increase in tensile strength from 4.8 ± 0.4 to 6.9 ± 1.2 MPa after 14 days of culture. Importantly, the spatially confined delivery of BMP-2 within the spheroids increased mineral deposition and more than threefold enhanced osteogenic genes of cells in the bone layer while the cells induced by TGF-ß1 signals were apparently differentiated into chondrocytes within the cartilage layer. The results suggest that our composite spheroid-laden hydrogel could be used for the biofabrication of osteochondral tissue, which can be applied to engineer other complex tissues by delivery of appropriate biomolecules.
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Osteogênese , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta1/farmacologia , Hidrogéis/farmacologia , Engenharia Tecidual/métodos , Diferenciação Celular , Alicerces TeciduaisRESUMO
Inflammatory bowel disease (IBD) is an idiopathic inflammatory disorder characterized by chronic and relapsing manifestations. Several environmental factors are known as triggers for exacerbation of IBD. However, an association between exacerbation of IBD and ambient temperature is uncertain. This study aimed to estimate the risk of acute exacerbation of IBD due to ambient temperature. We performed a bidirectional case-crossover study using a nationwide claim data from South Korea. The external validation was conducted with a large prospective cohort in the United Kingdom. We confirmed significant associations between acute exacerbation of IBD and the short-term ambient temperature changes toward severe temperatures, in the cold weather (-19.4°C-4.3°C) (odd ratio [OR] = 1.13, 95% confidence interval [CI]: 1.13-1.14) and in the hot weather (21.3°C-33.5°C) (OR = 1.16, 95% CI: 1.15-1.17). However, the association was not significant in the moderate weather (4.3°C-21.3°C). The external validation suggested consistent results with additional elevation of acute exacerbation risk in the colder weather (-13.4°C to 2.6°C) (OR = 1.90, 95% CI: 1.62-2.22) and in the hotter weather (15.7°C-28.4°C) (OR = 1.41, 95% CI: 1.32-1.51). We observed and validated that the short-term ambient temperature changes were associated with acute exacerbation of IBD in the cold and hot weathers. Our findings provide evidence that temperature changes are associated with the acute exacerbation of IBD.
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Doenças Inflamatórias Intestinais , Tempo (Meteorologia) , Humanos , Temperatura , Estudos Cross-Over , Estudos Prospectivos , Temperatura Baixa , Temperatura AltaRESUMO
Oncolytic viruses are of significant clinical interest due to their ability to directly infect and kill tumors and enhance the anti-tumor immune response. Previously, we developed KLS-3010, a novel oncolytic virus derived from the International Health Department-White (IHD-W) strain vaccinia virus, which has robust tumoricidal effects. In the present study, we generated a recombinant oncolytic virus, KLS-3020, by inserting three transgenes (hyaluronidase [PH-20], interleukin-12 [IL-12], and soluble programmed cell death 1 fused to the Fc domain [sPD1-Fc]) into KLS-3010 and investigated its anti-tumor efficacy and ability to induce anti-tumor immune responses in CT26.WT and B16F10 mouse tumor models. A single injection of KLS-3020 significantly decreased tumor growth. The roles of the transgenes were investigated using viruses expressing each single transgene alone and KLS-3020. PH-20 promoted virus spread and tumor immune cell infiltration, IL-12 activated and reprogrammed T cells to inflammatory phenotypes, and sPD1-Fc increased intra-tumoral populations of activated T cells. The tumor-specific systemic immune response and the abscopal tumor control elicited by KLS-3020 were demonstrated in the CT26.WT tumor model. The insertion of transgenes into KLS-3020 increased its anti-tumor efficacy, supporting further clinical investigation of KLS-3020 as a novel oncolytic immunotherapy.
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Fluidic microphysiological systems (MPS) are microfluidic cell culture devices that are designed to mimic the biochemical and biophysical in vivo microenvironments of human tissues better than conventional petri dishes or well-plates. MPS-grown tissue cultures can be used for probing new drugs for their potential primary and secondary toxicities as well as their efficacy. The systems can also be used for assessing the effects of environmental nanoparticles and nanotheranostics, including their rate of uptake, biodistribution, elimination, and toxicity. Pumpless MPS are a group of MPS that often utilize gravity to recirculate cell culture medium through their microfluidic networks, providing some advantages, but also presenting some challenges. They can be operated with near-physiological amounts of blood surrogate (i.e., cell culture medium) that can recirculate in bidirectional or unidirectional flow patterns depending on the device configuration. Here we discuss recent advances in the design and use of both pumped and pumpless MPS with a focus on where pumpless devices can contribute to realizing the potential future role of MPS in evaluating nanomaterials. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.
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Dispositivos Lab-On-A-Chip , Sistemas Microfisiológicos , Humanos , Distribuição Tecidual , Microfluídica , Descoberta de DrogasRESUMO
The issue of self-neglect among older adults is receiving attention in modern societies where aging is accelerating. To help expand our understanding of this phenomenon, this study identified its different types using latent profile analysis and verified the main variables that distinguish these types from each other. The three profiles that were identified are high self-neglect (HSN: 28.8%), low self-neglect (LSN: 35.6%), and poor personal hygiene (PPH: 35.6%). Interestingly, PPH showed a high rate and was identified as a noticeable type of elder self-neglect. Gender, age group, SES, support size, and suicidal ideation were significant in classifying the types of self-neglect. Men were more likely to be within the HSN group, and late elderly were more likely to be within the PPH group. The higher SES and social support, the higher the probability of being within the LSN group. The higher the suicidal ideation, the higher the possibility of falling under the HSN group. To reduce self-neglect among older adults, this study suggests to older adults vulnerable to self-neglect, expansion of the social support available to them, and provision of mental health services to this population.
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Balanced activities of matrix metalloproteinases (MMPs) and their inhibitors are essential for photoreceptor (PR) cell survival. PR rod cell survival in rodent models of inherited retinitis pigmentosa (RP) is prolonged by recombinant tissue inhibitor of metalloproteinase (TIMP)-1 or clusterin (CLU) proteins. Retinal pigment epithelial cells (RPE) and Müller glia (MG) cells support PR cells. In human RPE and MG cell lines, we measured their mRNA levels of the two genes with quantitative real-time PCR (qRT-PCR) with interleukin (IL)-1ß treatment, a key pathological component in retinal degeneration. Endogenous CLU gene expression was significantly downregulated by IL-1ß in both cell types, whereas TIMP-1 expression was upregulated in MG cells, suggesting the transcriptional control of CLU is potentially more sensitive to inflammatory conditions. The expression levels of CLU endocytic receptors revealed that the low-density lipoprotein receptor-related protein 2 (LRP2) was upregulated only in MG cells by the treatment with no detectable change in RPE cells. Like LRP2, IL-1ß upregulated TIMP-1 receptor LRP1 expression in MG cells; however, it was decreased in the expression of RPE cells. These data suggest that the gene expression of CLU and TIMP-1 and their receptors may be dynamically modulated in inflammatory conditions.