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The involvement of nuclear factor Y (NF-Y) in transcriptional reprogramming during arbuscular mycorrhizal symbiosis has been demonstrated in several plant species. However, a comprehensive picture is lacking. We showed that the spatial expression of NF-YC3 was observed in cortical cells containing arbuscules via the cis-regulatory element GCC boxes. Moreover, the NF-YC3 promoter was transactivated by the combination of CYCLOPS and autoactive calcium and calmodulin-dependent kinase (CCaMK) via GCC boxes. Knockdown of NF-YC3 significantly reduced the abundance of all intraradical fungal structures and affected arbuscule size. BCP1, SbtM1, and WRI5a, whose expression associated with NF-YC3 levels, might be downstream of NF-YC3. NF-YC3 interacted with NF-YB3a, NF-YB5c, or NF-YB3b, in yeast (Saccharomyces cerevisiae) and in planta, and interacted with NF-YA3a in yeast. Spatial expression of three NF-YBs was observed in all cell layers of roots under both mock and mycorrhizal conditions. Simultaneous knockdown of three NF-YBs, but not individually, reduced the fungal colonization level, suggesting that there might be functional redundancy of NF-YBs to regulate AM symbiosis. Collectively, our data suggest that NF-YC3 and NF-YBs positively regulate AM symbiosis in tomato, and arbuscule-related NF-YC3 may be an important downstream gene of the common symbiosis signaling pathway.
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Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies globally, representing a significant public health problem with a poor prognosis. The development of efficient therapeutic strategies for HNSCC prevention and treatment is urgently needed. The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved transduction network in eukaryotic cells that promotes cell survival, growth, and cycle progression. Dysfunction in components of this pathway, such as hyperactivity of PI3K, loss of PTEN function, and gain-of-function mutations in AKT, are well-known drivers of treatment resistance and disease progression in cancer. In this review, we discuss the major mutations and dysregulations in the PAM signaling pathway in HNSCC. We highlight the results of clinical trials involving inhibitors targeting the PAM signaling pathway as a strategy for treating HNSCC. Additionally, we examine the primary mechanisms of resistance to drugs targeting the PAM pathway and potential therapeutic strategies.
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Community inclusion is a human right for all people, including people with mental illness. It is also an important part of individualized support to enable people experiencing mental illness to live in their preferred communities and to recover. In Taiwan, no study has investigated the social experiences of healthcare professionals. To fill this knowledge gap and inform ongoing mental health system strengthening, this study examined the not-in-my-backyard (NIMBY) phenomenon observed while establishing community mental health clubhouses in Taiwan and corresponding experiences of community inclusion. Data were collected through semi-structured interviews of 16 purposively sampled frontline healthcare professionals from Taiwanese mental health clubhouses. Data were analyzed using qualitative content analysis. Two themes were identified: "NIMBY phenomenon: Community residents' resistance to clubhouses" and "Measures adopted by the clubhouse for community inclusion". Two categories with eleven subcategories emerged. The findings demonstrate the following conclusions. First, the NIMBY phenomenon is related to the stigmatization and discrimination faced by individuals with mental disorders in society. Second, in Asian societies, mental disorders are associated with a particular social and cultural context. Third, the fear and rejection of individuals with mental disorders deepen their social exclusion. Forth, community mental health clubhouse models employ seven strategic approaches to community inclusion, listed as follows: capacity building for individuals, direct interaction with the public through community activities, provision of community services, life skills training, repairing and managing neighborhood relationships, assisting individuals in obtaining community employment, and conducting social education for community residents. Clearly, we need to combat social exclusion of people with mental illness and promote inclusive and accessible services and systems across sectors.
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Hepatic lipid metabolism is modulated by the circadian rhythm; therefore, circadian disruption may promote obesity and hepatic lipid accumulation. This study aims to investigate dietary pterostilbene (PSB) 's protective effect against high-fat-diet (HFD)-induced lipid accumulation exacerbated by chronic jet lag and the potential role of gut microbiota therein. Mice were treated with a HFD and chronic jet lag for 14 weeks. The experimental group was supplemented with 0.25% (w/w) PSB in its diet to evaluate whether PSB had a beneficial effect. Our study found that chronic jet lag exacerbates HFD-induced obesity and hepatic lipid accumulation, but these adverse effects were significantly mitigated by PSB supplementation. Specifically, PSB promoted hepatic lipolysis and ß-oxidation by upregulating SIRT1 expression, which indirectly reduced oxidative stress caused by lipid accumulation. Additionally, the PSB-induced elevation of SIRT1 and SIRT3 expression helped prevent excessive autophagy and mitochondrial fission by activating Nrf2-mediated antioxidant enzymes. The result was evidenced by the use of SIRT1 and SIRT3 inhibitors in in vitro studies, which demonstrated that activation of SIRT1 and SIRT3 by PSB is crucial for the translocation of PGC-1α and Nrf2, respectively. Moreover, the analysis of gut microbiota suggested that PSB's beneficial effects were partly due to its positive modulation of gut microbial composition and functionality. The findings of this study suggest the potential of dietary PSB as a candidate to improve hepatic lipid metabolism via several mechanisms. It may be developed as a treatment adjuvant in the future.
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Dieta Hiperlipídica , Síndrome do Jet Lag , Metabolismo dos Lipídeos , Fígado , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Sirtuína 1 , Sirtuína 3 , Estilbenos , Animais , Sirtuína 1/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos , Masculino , Metabolismo dos Lipídeos/efeitos dos fármacos , Estilbenos/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Sirtuína 3/metabolismo , Síndrome do Jet Lag/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade , Suplementos NutricionaisRESUMO
Although the pathogenetic pathway of moyamoya disease (MMD) remains unknown, studies have indicated that variations in the RING finger protein RNF 213 is the strongest susceptible gene of MMD. In addition to the polymorphism of this gene, many circulating angiogenetic factors such as growth factors, vascular progenitor cells, inflammatory and immune mediators, angiogenesis related cytokines, as well as circulating proteins promoting intimal hyperplasia, excessive collateral formation, smooth muscle migration and atypical migration may also play critical roles in producing this disease. Identification of these circulating molecules biomarkers may be used for the early detection of this disease. In this chapter, how the hypothesized pathophysiology of these factors affect MMD and the interactive modulation between them are summarized.
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Biomarcadores , Doença de Moyamoya , Ubiquitina-Proteína Ligases , Humanos , Adenosina Trifosfatases/genética , Biomarcadores/metabolismo , Biomarcadores/sangue , Doença de Moyamoya/genética , Doença de Moyamoya/diagnóstico , Ubiquitina-Proteína Ligases/genéticaRESUMO
A Pd-catalyzed regioselective hydroarylation of terminal alkynes containing a heteroatom has been developed via carbopalladation for the synthesis of allylic ethers, amines, and homoallylic alcohols. Moreover, hydroalkenylation of alkynes produces a variety of stereodefined 1,4-dienes with high regioselectivity. The important features of the present protocol are that it is highly regioselective, operationally rapid, and scalable with a huge substrate scope using only 3 mol% of PdCl2(PPh3)2 catalyst in the presence of a mild base KOAc.
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Taiwanese community mental health facilities encounter opposition/resistance from residents, commonly known as "Not-In-My-Backyard" (NIMBYism). This study investigated NIMBYism during the establishment of such facilities and how they respond to such resistance. A qualitative study through semi-structured interviews was used to obtain purposively sampled data. Fifteen frontline healthcare professionals from community mental health facilities in Taiwan were interviewed individually, using an organizational analysis structure. Data were analyzed using qualitative content analysis. Two themes: "Reasons for Resident Resistance" and "Institutional Response Strategies", two categories, and 11 subcategories emerged. The findings demonstrated the following: (1) Reasons behind residents' resistance toward establishing community mental health facilities are diverse. (2) Communities lack understanding regarding people with mental disorders, leading to irrational beliefs. (3) Fear and negative perceptions toward people with mental disorders exist. (4) Strategies employed by the facilities include providing community services to foster amicable relationships, organizing community outreaches, training people with mental disorders within communities, nurturing neighborhood connections, establishing and sustaining friendships within communities, inviting residents to visit community mental health facilities or introducing the facilities to communities, and leveraging governmental support. The government should adopt regulations or laws to reduce discrimination, promote human rights, and legislate to demarcate the use of community land.
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BACKGROUND: Metabolic associated steatohepatitis (MASH) is metabolic disease that may progress to cirrhosis and hepatocellular carcinoma. Mouse models of diet-induced MASH, which is characterized by the high levels of fats, sugars, and cholesterol in diets, are commonly used in research. However, mouse models accurately reflecting the progression of MASH in humans remain to be established. Studies have explored the potential use of serological metabolites as biomarkers of MASH severity in relation to human MASH. METHODS: We performed a comparative analysis of three mouse models of diet-induced MASH in terms of phenotypic and metabolomic characteristics; MASH was induced using different diets: a high-fat diet; a Western diet; and a high-fat, high-cholesterol diet. Liver cirrhosis was diagnosed using standard clinical approaches (e.g., METAVIR score, hyaluronan level, and collagen deposition level). Mouse serum samples were subjected to nuclear magnetic resonance spectroscopy-based metabolomic profiling followed by bioinformatic analyses. Metabolomic analysis of a retrospective cohort of patients with hepatocellular carcinoma was performed; the corresponding cirrhosis scores were also evaluated. RESULTS: Using clinically relevant quantitative diagnostic methods, the severity of MASH was evaluated. Regarding metabolomics, the number of lipoprotein metabolites increased with both diet and MASH progression. Notably, the levels of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) significantly increased with fibrosis progression. During the development of diet-induced MASH in mice, the strongest upregulation of expression was noted for VLDL receptor. Metabolomic analysis of a retrospective cohort of patients with cirrhosis indicated lipoproteins (e.g., VLDL and LDL) as predominant biomarkers of cirrhosis. CONCLUSIONS: Our findings provide insight into the pathophysiology and metabolomics of experimental MASH and its relevance to human MASH. The observed upregulation of lipoprotein expression reveals a feedforward mechanism for MASH development that may be targeted for the development of noninvasive diagnosis.
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OBJECTIVE: Ovarian clear cell carcinoma has a poor prognosis in comparison with other pathological types of epithelial ovarian carcinoma. It also has relative resistance to first-line platinum-based chemotherapy with a great risk of recurrence. CASE REPORT: We report a case of recurrent ovarian clear cell carcinoma status after left salpingo-oophorectomy (fertility-sparing debulking operation) and six courses of adjuvant chemotherapy (paclitaxel (175 mg/m2)/carboplatin (AUC 6)). However, two years after diagnosis, elevated CA-125 accompanied by an intrapelvic mass was noted. Uterine intramural recurrence was found during the second laparotomy. She was treated with right salpingo-oophorectomy and abdominal hysterectomy combined with systemic chemotherapy administration (paclitaxel (175 mg/m2)/carboplatin (AUC 6)) and maintenance therapy (bevacizumab (7.5 mg/kg)). There was no other recurrence until one and a half years postoperatively, and the patient was tumor free with regular follow-up. CONCLUSION: In young patients with stage I ovarian clear cell carcinoma, fertility-sparing surgery was considered. Most patients will suffer from tumor recurrence, and also intrauterine recurrence rarely happen.
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Adenocarcinoma de Células Claras , Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Carboplatina , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia , Paclitaxel/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Adenocarcinoma de Células Claras/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
The [4 + 2] annulation of ß-formyl ketones with an indole has been developed for the regioselective synthesis of diphenyl-substituted carbazoles in the presence of a catalytic amount of iodine. The 1,4-dicarbonyl compound containing a phenyl group at the α-position of an aldehyde group reacts more readily with indoles to form carbazole derivatives. Using this method, a variety of carbazole derivatives can be readily accessed under mild reaction conditions.
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BACKGROUND: The prevalence of oral diseases among Taiwanese prisoners has rarely been investigated. This study aimed to estimate the gender-specific prevalence of oral disease in a sample of Taiwanese prisoners. METHODS: We included 83,048 participants from the National Health Insurance (NHI) Program. Outcomes were measured using the clinical version of the International Classification of Diseases, Ninth Revision (ICD-9-CM). For prevalence, we provide absolute values and percentages. We also performed a χ2 test to assess sex and age group differences in the percentage of disease in the oral cavity, salivary glands, and jaw. RESULTS: The prevalence rate of oral diseases was 25.90%, which was higher than that of the general population. The prevalence of oral diseases in female prisoners was higher than that in male prisoners (p < 0.001), and the prevalence of oral diseases in prisoners aged ≤ 40 was higher than that of prisoners aged > 40. Among all cases of diagnosed oral diseases, the top three diseases were dental hard tissue diseases (13.28%), other cellulitis and abscesses (9.79%), and pruritus and related conditions (2.88%), respectively. The prevalence of various oral diseases in female prisoners was significantly higher than that in male prisoners. CONCLUSION: Oral disease is common among Taiwanese prisoners. Female prisoners had a higher prevalence of oral, salivary gland, and jaw diseases than male prisoners. Therefore, early prevention and appropriate treatment are required and also a need for gender-specific oral disease products given the differences in the prevalence of oral disease among male and female prisoners.
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Saúde Bucal , Prisioneiros , Humanos , Masculino , Feminino , Estudos Transversais , Fatores Sexuais , Taiwan/epidemiologia , PrevalênciaRESUMO
This Letter outlines palladium-catalyzed regioselective (Markovnikov's) addition of aryl boronic acids to propargyl 1,3-dicarbonyl alkyne to accomplish olefinic/diene 1,3-dicarbonyl compounds without the need for water workup. This methodology showcases remarkable performance with wide-ranging substrate diversity, achieving high yields while employing merely 3 mol % [Pd] alongside a mild KOAc base. Moreover, the utility of dicarbonyl olefins is exemplified through their application in intramolecular cyclization and debenzoylation reactions to access valuable trisubstituted pyran building blocks and (E)-4-methylene-1,6-diphenylhex-5-en-1-one synthesis.
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All countries recognize the importance of enhancing circular resource utilization and promoting zero waste in order to achieve a circular economy. This study focuses on 22 counties (cities) in Taiwan and analyses the relationship between changes in resource recovery efficiency and productivity over an 8-year period (2011-2018) using the super efficiency directional distance function and total factor productivity. The results indicate that the average total efficiency of resource recovery in the 22 counties (cities) is 1.3951, with 17 counties (cities) exceeding 1. The average gross productivity of resource recovery is 1.0417, and only four counties have a gross productivity of less than 1. Despite having more administrative resources, municipalities directly under the central government have a slightly lower average total efficiency of resource recovery (1.1464) than non-municipalities (1.4885). To improve efficiency, the government should allocate resources rationally and upgrade technology. The study's findings can serve as a reference for the 22 counties (cities) in Taiwan and provide guidance for municipal governments worldwide in developing policies related to resource recovery.
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Parkinson's disease (PD) is featured mainly by the loss of dopaminergic neurons and the presence of α-synuclein-containing aggregates in the substantia nigra of brain. The α-synuclein fibrils and aggregates lead to increased oxidative stress and neural toxicity in PD. Chronic inflammation mediated by microglia is one of the hallmarks of PD pathophysiology. In this report, we showed that coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 reduced the expression of major histocompatibility complex-II, NLR family pyrin domain containing (NLRP) 3, caspase-1, inducible nitric oxide synthase, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in α-synuclein-activated mouse BV-2 microglia. Release of pro-inflammatory mediators including nitric oxide, IL-1ß, IL-6 and TNF-α was also mitigated. In BE(2)-M17 cells expressing A53T α-synuclein aggregates, LM-021 and NC009-1 reduced α-synuclein aggregation, neuroinflammation, oxidative stress and apoptosis, and promoted neurite outgrowth. These protective effects were mediated by downregulating NLRP1, IL-1ß and IL-6, and their downstream pathways including nuclear factor (NF)-κB inhibitor alpha (IκBα)/NF-κB P65 subunit (P65), c-Jun N-terminal kinase (JNK)/proto-oncogene c-Jun (JUN), mitogen-activated protein kinase 14 (P38)/signal transducer and activator of transcription (STAT) 1, and Janus kinase 2 (JAK2)/STAT3. The study results indicate LM-021 and NC009-1 as potential new drug candidates for PD.
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Chalconas , Doença de Parkinson , Camundongos , Animais , alfa-Sinucleína/metabolismo , Chalconas/farmacologia , Interleucina-6/metabolismo , Inflamação/metabolismo , Estresse Oxidativo , Indóis/farmacologia , NF-kappa B/metabolismo , Doença de Parkinson/metabolismo , Microglia/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Cumarínicos/farmacologia , Lipopolissacarídeos/farmacologiaRESUMO
We report on a copper-catalyzed three-component reaction for the synthesis of disubstituted nicotinonitriles using 3-bromopropenals, benzoylacetonitriles, and ammonium acetate (NH4OAc). The Knoevenagel-type condensation of 3-bromopropenals with benzoylacetonitriles gives δ-bromo-2,4-dienones that contain strategically placed functional groups that react with the ammonia generated in situ to give the corresponding azatrienes. These azatrienes can then be transformed into trisubstituted pyridines under the reaction conditions via a reaction sequence involving 6π-azaelectrocyclization and aromatization.
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Studies of the neurobiological causes of anxiety disorders have suggested that the γ-aminobutyric acid (GABA) system increases synaptic concentrations and enhances the affinity of GABAA (type A) receptors for benzodiazepine ligands. Flumazenil antagonizes the benzodiazepine-binding site of the GABA/benzodiazepine receptor (BZR) complex in the central nervous system (CNS). The investigation of flumazenil metabolites using liquid chromatography (LC)-tandem mass spectrometry will provide a complete understanding of the in vivo metabolism of flumazenil and accelerate radiopharmaceutical inspection and registration. The main goal of this study was to investigate the use of reversed-phase high performance liquid chromatography (PR-HPLC), coupled with electrospray ionization triple-quadrupole tandem mass spectrometry (ESI-QqQ MS), to identify flumazenil and its metabolites in the hepatic matrix. Carrier-free nucleophilic fluorination with an automatic synthesizer for [18F]flumazenil, combined with nano-positron emission tomography (NanoPET)/computed tomography (CT) imaging, was used to predict the biodistribution in normal rats. The study showed that 50% of the flumazenil was biotransformed by the rat liver homogenate in 60 min, whereas one metabolite (M1) was a methyl transesterification product of flumazenil. In the rat liver microsomal system, two metabolites were identified (M2 and M3), as their carboxylic acid and hydroxylated ethyl ester forms between 10 and 120 min, respectively. A total of 10-30 min post-injection of [18F]flumazenil showed an immediate decreased in the distribution ratio observed in the plasma. Nevertheless, a higher ratio of the complete [18F]flumazenil compound could be used for subsequent animal studies. [18F] According to in vivo nanoPET/CT imaging and ex vivo biodistribution assays, flumazenil also showed significant effects on GABAA receptor availability in the amygdala, prefrontal cortex, cortex, and hippocampus in the rat brain, indicating the formation of metabolites. We reported the completion of the biotransformation of flumazenil by the hepatic system, as well as [18F]flumazenil's potential as an ideal ligand and PET agent for the determination of the GABAA/BZR complex for multiplex neurological syndromes at the clinical stage.
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OBJECTIVE: Past vegetarians research has often found that they have lower blood pressure (BP). Effects may include their lower BMI and higher intake levels of fruit and vegetables. Besides, the study pursues to extend this evidence in a diverse population containing vegans, lacto-ovo vegetarians and omnivores. DESIGN: The study analyzed data on five hundred vigorous individuals aged 20 years or older from a standard medical screening program and provided validated questionnaire. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. SETTING: Health screening programs were conducted at a standard medical screening program in Taiwan between 2006 and 2017. Dietary data were gathered by self-administered questionnaire. SUBJECTS: Five hundred Taiwanese subjects representing the cohort. RESULTS: Multiple regression analyses confirmed that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Taiwanese (ß = - 6.8, p < 0.05 and ß = - 6.9, p < 0.001). Findings for lacto-ovo vegetarians (ß = - 9.1, p < 0.001 and ß = - 5.8, p < 0.001) were similar. The vegetarians were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or routine of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0.37 (95% CI = 0.19-0.74), 0.57 (95% CI = 0.36-0.92) and 0.92 (95% CI = 0.50-1.70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Results were reduced after adjustment for BMI. CONCLUSIONS: The study concludes from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores.
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Anti-Hipertensivos , Hipertensão , Humanos , Pressão Sanguínea , Taiwan , Estudos Prospectivos , Dieta Vegetariana , Hipertensão/epidemiologia , Hipertensão/prevenção & controleRESUMO
The sterilisation of surgical instruments is a major factor in infection control in the operating room (OR). All items used in the OR must be sterile for patient safety. Therefore, the present study evaluated the effect of far-infrared radiation (FIR) on the inhibition of colonies on packaging surface during the long-term storage of sterilised surgical instruments. From September 2021 to July 2022, 68.2% of 85 packages without FIR treatment showed microbial growth after incubation at 35 °C for 30 days and at room temperature for 5 days. A total of 34 bacterial species were identified, with the number of colonies increasing over time. In total, 130 colony-forming units were observed. The main microorganisms detected were Staphylococcus spp. (35%) and Bacillus spp. (21%) , Kocuria marina and Lactobacillus spp. (14%), and mould (5%). No colonies were found in 72 packages treated with FIR in the OR. Even after sterilisation, microbial growth can occur due to movement of the packages by staff, sweeping of floors, lack of high-efficiency particulate air filtration, high humidity, and inadequate hand hygiene. Thus, safe and simple far-infrared devices that allow continuous disinfection for storage spaces, as well as temperature and humidity control, help to reduce microorganisms in the OR.
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Bactérias , Desinfecção , Humanos , Salas Cirúrgicas , Embalagem de Alimentos , Instrumentos Cirúrgicos , Contagem de Colônia MicrobianaRESUMO
This study aims to examine the effectiveness of chair yoga therapy on improving functional status and daily life activity scores in older female adults with knee osteoarthritis living in the community. A quasi-experimental design was adopted. In total, 85 female participants with knee osteoarthritis were assigned to the chair yoga therapy intervention group (n = 43) or the comparison (n = 42) group. A 12-week chair yoga exercise program was provided to the intervention group two times per week from January to April 2020. The primary outcomes, which include changes in physical functional ability, body mass index, and biophysiological indicators, were evaluated for all participants in the pre- and post-measures time periods. The analysis shows that the participants had a significantly higher level of functional fitness and daily life activity scores after the chair yoga intervention. This finding indicates that the chair yoga program was effective in improving the functional fitness and daily life activity scores of community-dwelling elderly females with knee osteoarthritis.
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The iodine-catalyzed cascade reaction of ortho-formylarylketones with indoles for the synthesis of indolylbenzo[b]carbazoles is reported. The reaction is initiated in the presence of iodine by two successive nucleophilic additions of indoles with an aldehyde group of ortho-formylarylketones, and the ketone does not undergo a nucleophilic addition and only involves in the Friedel-Crafts-type cyclization. A variety of substrates are tested, and the efficiency of this reaction is demonstrated with gram-scale reactions.