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Purpose: To perform a meta-analysis and systematic review to compare the efficacy and complications of micropulse laser trabeculoplasty (MLT) and selective laser trabeculoplasty (SLT) in adult patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). Methods: We performed a systematic review utilizing PubMed, Embase, and Scopus, on April 8, 2024. Meta-analyses were performed for the mean change in intraocular pressure (IOP) at one-month, six-month, and one-year follow-up visits, rate of IOP spikes (>5 mmHg increase from the pre-procedure baseline IOP), rate of treatment failure (<20% or <3 mmHg reduction in IOP or requiring additional medications or procedures), and mean change in number of medications. Results: Six studies, with a total of 593 eyes, were included: 283 underwent MLT, while 310 underwent SLT. A statistically significant difference in the efficacy of MLT versus SLT at one-month and six-month follow-ups was present, with SLT reducing IOP by 0.83 mmHg (95% CI: 0.20, 1.47; P = 0.01) more and 0.55 mmHg (95% CI: 0.02, 1.08; P = 0.04) more than MLT, respectively. At the one-year follow-up, there was no significant disparity in IOP reduction between SLT and MLT (WMD = 0.16; 95% CI: -0.40, 0.71; P = 0.58). There was a significantly lower rate of IOP spikes in the MLT treatment group (RR = 0.37; 95% CI: 0.16, 0.89; P = 0.03). There was no statistically significant difference in the rate of treatment failures (RR = 1.05; 95% CI: 0.68, 1.62; P = 0.84) or number of topical medications reduced (WMD = 0.06; 95% CI: -0.13, 0.26; P = 0.53). Conclusion: While SLT may offer greater short-term reductions in IOP, it may be associated with more postoperative IOP spikes when compared to MLT. At one-year follow-up, there were no significant differences in IOP reduction or failure rates between the MLT and SLT groups.
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Background: Tobacco usage is a major global public health concern, contributing to millions of deaths annually. This study focuses on security guards, an occupational group facing unique challenges, to investigate tobacco prevalence, usage patterns, and associated oral health risks. Methods: A cross-sectional study was conducted among security guards at a Tertiary Health Care Centre, from October 2022 to February 2023. Data on demographics, tobacco habits, and comorbidities were collected via a structured questionnaire. Clinical oral examinations provisionally diagnosed Oral Potentially Malignant Disorders (OPMDs) based on clinical findings. Appropriate Statistical analyses were employed. Results: Among 696 security guards, 40.1% used tobacco, including 15.0% smokers and 74.5% engaging in smokeless tobacco. Additionally, 10.3% reported using both smoking and smokeless forms. Non-tobacco users accounted for 59.9%. Tobacco users showed a higher prevalence of OPMDs (11.4%) compared to non-tobacco users (1.4%). Discussion: Security guards demonstrated a higher tobacco prevalence, with smokeless tobacco being predominant. Gender disparities in tobacco use emphasize the need for gender-specific interventions. The study highlights the significant impact of tobacco on oral health, especially the risk of OPMDs. Conclusion: A high prevalence of tobacco usage (40.1%), particularly smokeless tobacco, among security guards, emphasizes the importance of targeted interventions within this occupational group. Oral Potentially Malignant Disorders (OPMDs) were significantly more prevalent (11.4%) in tobacco users. The association between tobacco usage and OPMDs reaffirms the well-established association between tobacco and adverse oral health outcomes.
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When stressed, cells need to adapt their proteome to maintain protein homeostasis. This requires increased proteasome assembly. Increased proteasome assembly is dependent on increased production of proteasome assembly chaperones. In Saccharomyces cerevisiae, inhibition of the growth-promoting kinase complex TORC1 causes increased proteasome assembly chaperone translation, including that of Adc17. This is dependent upon activation of the mitogen-activated protein kinase (MAPK) Mpk1 and relocalisation of assembly chaperone mRNA to patches of dense actin. We show here that TORC1 inhibition alters cell wall properties to induce these changes by activating the cell wall integrity pathway through the Wsc1, Wsc3 and Wsc4 sensor proteins. We demonstrate that, in isolation, these signals are insufficient to drive protein expression. We identify that the TORC1-activated S6 kinase Sch9 must be inhibited as well. This work expands our knowledge on the signalling pathways that regulate proteasome assembly chaperone production.
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Chaperonas Moleculares , Complexo de Endopeptidases do Proteassoma , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Transdução de Sinais , Parede Celular/metabolismo , Regulação Fúngica da Expressão Gênica , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
Peptidoglycan is a major constituent of the bacterial cell wall. Its integrity as a polymeric edifice is critical for bacterial survival and, as such, it is a preeminent target for antibiotics. The peptidoglycan is a dynamic crosslinked polymer that undergoes constant biosynthesis and turnover. The soluble lytic transglycosylase (Slt) of Pseudomonas aeruginosa is a periplasmic enzyme involved in this dynamic turnover. Using amber-codon-suppression methodology in live bacteria, we incorporated a fluorescent chromophore into the structure of Slt. Fluorescent microscopy shows that Slt populates the length of the periplasmic space and concentrates at the sites of septation in daughter cells. This concentration persists after separation of the cells. Amber-codon-suppression methodology was also used to incorporate a photoaffinity amino acid for the capture of partner proteins. Mass-spectrometry-based proteomics identified 12 partners for Slt in vivo. These proteomics experiments were complemented with in vitro pulldown analyses. Twenty additional partners were identified. We cloned the genes and purified to homogeneity 22 identified partners. Biophysical characterization confirmed all as bona fide Slt binders. The identities of the protein partners of Slt span disparate periplasmic protein families, inclusive of several proteins known to be present in the divisome. Notable periplasmic partners (KD < 0.5 µM) include PBPs (PBP1a, KD = 0.07 µM; PBP5 = 0.4 µM); other lytic transglycosylases (SltB2, KD = 0.09 µM; RlpA, KD = 0.4 µM); a type VI secretion system effector (Tse5, KD = 0.3 µM); and a regulatory protease for alginate biosynthesis (AlgO, KD < 0.4 µM). In light of the functional breadth of its interactome, Slt is conceptualized as a hub protein within the periplasm.
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Proteínas de Bactérias , Pseudomonas aeruginosa , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Periplasma/metabolismo , Periplasma/enzimologia , Proteínas Periplásmicas/metabolismo , Proteínas Periplásmicas/genética , Proteínas Periplásmicas/química , Glicosiltransferases/metabolismo , Glicosiltransferases/genética , Glicosiltransferases/química , Peptidoglicano/metabolismo , Peptidoglicano/químicaRESUMO
Introduction: This analysis examined changes in services received and service recovery one-year post-pandemic compared to pre-pandemic levels in children with ASD aged between 19 months and 17 years in various subgroups based on factors such as age, income, race/ethnicity, geographic location, and sex. Methods: An online, parent report survey was completed by the parents of children with ASD in the SPARK study cohort (N = 6,393). Descriptive statistics, chi-square analyses, and Spearman correlations were performed to study associations between various factors and service access, pre-pandemic and one-year, post-pandemic. Results: One year after pandemic, the lag in service recovery in children with ASD was greatest for PT/OT services followed by SLT. ABA services only recovered in half of the subgroups. In contrast, SES fully recovered and MH and MED services superseded pre-pandemic levels. Across majority of the timepoints, younger children received more SLT, PT/OT, and ABA services whereas older children received more SES, MH, and MED services. Higher income families accessed more SES, SLT, and ABA whereas lower income families received more MH services. White families received less SLT compared to non-white families. Hispanic families received more SLT services compared to non-Hispanic families. Compared to rural families, urban families received more ABA services at baseline which also recovered one year after the pandemic. Certain counterintuitive findings may be attributed to home/remote schooling leading to reduced access to related services. Conclusions: Future research and policy changes are needed to address the American healthcare vulnerabilities when serving children with ASD by enhancing the diversity of healthcare formats for continued service access during future pandemics and other similar crises.
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The dementia epidemic, attributed to aging populations, represents a growing socio-economic burden. It is estimated that in 2019 about 55 million people worldwide were living with dementia. With many possible causes of dementia and the possibility of mixed dementia combining Alzheimer's disease (AD) and vascular dementia the question is whether diagnostic uncertainty exists or whether diagnostic constructs based on single etiologies are incorrect. Vascular Cognitive Impairment and Dementia (VCID) designates the extent of cognitive dysfunctions from the most benign state to that of dementia, of vascular origin. We reviewed epidemiological, pathophysiological and clinical data on VCID with a focus on VaD, as well as key data on the development of a new therapeutic solution, SaiLuoTong (MLC-SLT). From documentary research executed on different web sources (PubMed, Clintrials.gov, Z-library and Google), our initial selection for the short review of VCID and VaD was based on keywords contained in each paragraph subtitles of this article with exclusion of publications in a language other than English or published before 2010. For the review of SaiLuoTong development, there was just the language exclusion criterion. Sorted by relevance and publication date, 47 references were selected from 140 shortlisted for review. With new evidence-based classification systems, vascular cognitive impairment was proposed as umbrella term covering all forms of cognitive deficits related to vascular causes. The scope of application expanded with the VCID which includes VaD and mixed pathologies. No drugs are approved for the treatment of VaD by major Western regulatory agencies, while some traditional Chinese medicines are registered in China. VCID treatment should have a dual focus: managing the underlying cerebrovascular disease and dementia symptoms. This is the objective set for the development of the MLC-SLT, the essential data of which are reviewed in detail. To strengthen VCID and VaD research, consensus groups should attempt to consolidate scattered local research initiatives into coordinated international programs. In two VaD clinical trials, MLC-SLT improved cognitive symptoms and activities of daily living, with good safety and potential disease-modifying effect. In a placebo-controlled study in 325 patients with mild to moderate VaD and randomized according to a delayed-start design, MLC-SLT demonstrated significant improvement in memory tests and performance in executive function tasks, expanding its place in the management of VCID. At week 26, changes in VADAS-cog scores (SD) from baseline were 23.25 (0.45) for MLC-SLT 180 mg bid), 23.05 (0.45) for MLC-SLT 120 mg bid (both p < 0.0001), and 20.57 (0.45) for placebo (p = 0.15). At week 52, differences between both groups MLC-SLT and placebo were 2.67 and 2.48, respectively (p < 0.0001), without significant difference between MLC-SLT groups.
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Purpose: This work demonstrates significant advantages in ophthalmic surgeries through the use of picosecond ultrashort laser pulses instead of state-of-the-art nanosecond laser pulses. These ultrashort lasers shall serve as universal tools more effectively combining advantages of high precision, low impact and economic advantages compared to existing instruments. Methods: As samples, we used post-mortem porcine eyes on which we performed the experiments with both picosecond and nanosecond lasers. Performed surgeries were laser iridotomy, (post-) cataract treatment/capsulotomy and selective laser-trabeculoplasty. Pulse widths were between 12 ps and 220 ns with pulse energies between 30 µJ and 10 mJ at 532 nm and 1,064 nm. Additionally, we investigated accompanying shock waves, cavitation bubbles, and heat effects during the ablation processes. Results: For all surgeries, significant differences were observed between picosecond and nanosecond pulses: It was possible to scale the pulse energy down to 10 of microjoules rather than requiring millijoules, and resulting tissue ablations are much more precise, more deterministic and less frayed. The shock wave and cavitation bubble investigation revealed major differences in pressure between picosecond pulses (0.25 MPa, 50 µJ) and nanosecond pulses (37 MPa, 5 mJ). The heat input during ablation could be lowered by two orders of magnitude. Conclusion: Picosecond ultrashort laser pulses show substantial benefits for several ophthalmic surgeries, with regard to ablation precision, shock wave generation and heat input. They are better than state-of-the-art ophthalmic nanosecond lasers in all aspects tested.
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PURPOSE: Glaucoma is the second leading cause of blindness worldwide. Early detection and timely treatment are crucial to reducing disease progression. Selective laser trabeculoplasty (SLT) has proven efficacious as a primary treatment for primary open-angle glaucoma. This study aims to evaluate the acceptance among Saudi ophthalmologists of using SLT as a primary treatment for glaucoma. METHODS: This cross-sectional study enrolled 128 ophthalmologists practicing in Saudi Arabia. Data collection was conducted using a structured online questionnaire, which evaluated sociodemographic data, current glaucoma practice, the technology acceptance model (TAM), and potential barriers to incorporating SLT as the primary treatment for glaucoma. RESULTS: The mean age of the participants was 40 ± 9.6 years, with 65.6% being male. Almost one-third were glaucoma specialists, and 89% followed the American Academy of Ophthalmology recommendations for managing glaucoma patients. The majority (96.1%) used medical treatment as the initial therapy, 72.7% agreed that SLT is safe, and 59.4% agreed that it rapidly controls intraocular pressure. Nearly half of the participants were willing to use SLT as the primary treatment, yet only 42.2% considered themselves experienced enough to do so. The most reported barriers were inadequate training (47.7%), non-availability of SLT equipment (41.4%), and low efficacy as reported by 27.3% of participants. CONCLUSION: Despite the good overall acceptance of SLT as a first-line treatment for glaucoma, most participants still preferred medical therapy as the primary treatment. To overcome the barriers to incorporating SLT, Saudi ophthalmologists require more training and access to equipment to effectively implement this modality in their practices.
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Background: Patients who have had laryngectomy require a thorough preoperative assessment for potential stomal stenosis, and an action plan for possible inadvertent displacement of the voice prosthesis (VP) must be considered. We report the anesthetic management of a post-laryngectomy patient undergoing lung resection surgery. The patient had both a laryngectomy and a VP in situ. Case Description: A 66-year-old man with Parkinson's disease, who had previously undergone total laryngectomy for supraglottic laryngeal cancer, had a cuffed tracheostomy tube and a VP inserted into the tracheoesophageal fistula below it. He was scheduled for segmentectomy combined with lymph node dissection under combined epidural-general anesthesia due to lung cancer in the apical segment of the right lung. Following induction of general anesthesia, instead of using a double-lumen endotracheal tube, we inserted a long spiral single-lumen tube (SLT) (6 mm inner diameter, 8.7 mm outer diameter) through the tracheostoma under the guidance of a 4 mm bronchoscope because of concerns about airway injury due to the narrowed diameter of the stoma and potential dislodgement of the VP. The tube was carefully advanced and smoothly placed into the left main bronchus, and the surgery was completed using one-lung ventilation (OLV). Conclusions: For post-total laryngectomy patients, it is important to assess the size and condition of the tracheostoma and the usage of a VP, and choose an appropriate endotracheal tube. A long spiral SLT might be an option for OLV in patients after laryngectomy with a tracheoesophageal VP.
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PURPOSE: To evaluate the long-term effect of laser trabeculoplasty (LTP) in patients randomized to multi-treatment in the Glaucoma Intensive Treatment Study (GITS). METHODS: Patients with untreated newly diagnosed open-angle glaucoma were treated with three intraocular pressure (IOP)-lowering substances for 1 week and then 360° argon or selective LTP was performed. IOP was measured just before LTP and repeatedly during the 60-month study period. Our previous report on 12 months follow-up data revealed no effect of LTP in eyes having an IOP <15 mmHg before the laser treatment. RESULTS: Before LTP, the mean IOP ± standard deviation in all 152 study-eyes of 122 multi-treated patients was 14.0 ± 3.5 mmHg. Three eyes of three deceased patients were lost to follow-up during the 60 months. After exclusion of eyes that received increased therapy during follow-up, the IOP was significantly reduced at all visits up to 48 months in eyes with pre-LTP IOP ≥15 mmHg; 2.6 ± 3.1 mmHg at 1 month and 1.7 ± 2.8 mmHg at 48 months, n = 56 and 48, respectively. No significant IOP reduction was seen in eyes with pre-LTP IOP <15 mmHg. Seven eyes, i.e., <13%, with pre-LTP IOP ≥15 mmHg at baseline had required increased IOP-lowering therapy at 48 months. CONCLUSION: LTP performed in multi-treated patients may provide a useful IOP reduction that is maintained over several years. This was true on a group level when the initial IOP was ≥15 mmHg, but if the pre-laser IOP was lower than that, chances of LTP success were small.
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Glaucoma de Ângulo Aberto , Glaucoma , Terapia a Laser , Hipotensão Ocular , Trabeculectomia , Humanos , Glaucoma de Ângulo Aberto/cirurgia , Seguimentos , Resultado do Tratamento , Glaucoma/cirurgia , Pressão Intraocular , Malha Trabecular/cirurgia , Hipotensão Ocular/cirurgiaRESUMO
PURPOSE: Selective laser trabeculoplasty (SLT) is a first-line treatment for glaucoma and ocular hypertension. However, due to insufficient comparative evidence in efficacy and safety, several SLT treatment protocols are currently used in practice. The objective of this trial was to compare the clinical outcomes of the 4 most significant SLT variants. DESIGN: Prospective, multicenter, masked, randomized controlled trial (RCT). PARTICIPANTS: Four hundred patients with glaucoma or ocular hypertension. The cohort consisted of both treatment-naive patients and patients undergoing glaucoma treatment, at different stages of disease. METHODS: Selective laser trabeculoplasty was performed with 50 ± 5 laser spots in 180 degrees or with 100 ± 10 spots in 360 degrees. The laser power was titrated to either just below the cavitation bubble level ("standard energy") or to a level producing cavitation bubbles at 50% to 75% of laser applications ("high energy"). Thus, 4 different treatment protocols were included - 180/standard, 180/high, 360/standard, and 360/high. The study adhered as close as possible to regular clinical management, but within a scientific framework. MAIN OUTCOME MEASURES: Reduction of intraocular pressure (IOP) 1 to 6 months after SLT. The proportion of patients achieving a 20% IOP reduction without any further intervention. Time to glaucoma treatment escalation in a Kaplan-Meier survival analysis. RESULTS: SLT performed with the 360/high protocol was shown to be superior regarding all primary endpoints. The IOP reduction 1 to 6 months after SLT was 5.4 mmHg in the 360/high group, compared to 3.4, 3.2, and 4.2 mmHg with the 180/standard, 180/high, and 360/standard protocols, respectively (P < 0.001). Furthermore, the success rate after 6 months was significantly higher -58.3%, compared with 30.2%, 29.3%, and 41.7% (P < 0.001). The median time to glaucoma treatment escalation was more than twice as long with 360/high SLT -1323 days, compared to 437 days, 549 days, and 620 days (P < 0.001). Although postoperative discomfort was more frequent with the 360/high protocol, symptoms were generally mild and transient. Adverse events were rare in all groups. CONCLUSIONS: The magnitude and longevity of SLT results increases substantially if SLT is performed according to the 360/high protocol, without compromising safety. Therefore, we recommend that 360/high SLT be considered as standard treatment. FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.
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Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Hipotensão Ocular , Trabeculectomia , Humanos , Trabeculectomia/métodos , Suécia , Resultado do Tratamento , Glaucoma/cirurgia , Glaucoma/diagnóstico , Hipotensão Ocular/cirurgiaRESUMO
Background and Objectives: The aim of the present study was to compare the short-term outcomes of selective laser trabeculoplasty (SLT) with argon laser trabeculoplasty (ALT) in patients with glaucoma in a real-world setting. Materials and Methods: The present study was conducted as a retrospective case-control study. The main outcome was the change in intraocular pressure (IOP) three months after laser surgery. In addition, the number of substances used for lowering of IOP and adverse events (AEs) were assessed. Results: Charts from 25 patients were included in the present study, of which 12 had received ALT and 13 SLT. In both groups, IOP significantly decreased from baseline values 6 weeks and 3 months after laser treatment (p < 0.01 vs. baseline at each timepoint for both groups). While after 6 weeks, no difference between groups was found, after 3 months, the decrease in IOP was significantly more pronounced in the SLT group (-26 ± 21% in the ALT group vs. -41 ± 14% in the SLT group, p = 0.018 between groups, ANOVA). Three months after laser treatment, the number of IOP-lowering substances used by each patient had decreased with no difference between groups (ALT: from 2.7 ± 0.8 to 2.3 ± 0.9 substances; SLT: from 1.8 ± 1.2 to 1.3 ± 1.1 substances, p = 0.386). Only a few AEs were observed. Two patients in the ALT and one patient in the SLT group required trabeculectomy within 1 year after laser treatment due to IOP decompensation. Conclusions: In the present study, SLT was at least as effective as ALT with fewer AEs and a similar reduction in concomitant IOP-lowering medication.
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Glaucoma de Ângulo Aberto , Glaucoma , Terapia a Laser , Hipertensão Ocular , Trabeculectomia , Humanos , Glaucoma de Ângulo Aberto/cirurgia , Argônio , Estudos Retrospectivos , Estudos de Casos e Controles , Áustria , Resultado do Tratamento , Glaucoma/cirurgia , Hipertensão Ocular/cirurgia , Pressão Intraocular , LasersRESUMO
Background: Salvage liver transplantation (SLT) has been reported to be an efficient treatment option for patients with recurrent hepatocellular carcinoma (HCC) after liver resection (LR). However, for recipients who underwent liver transplantation (LT) due to recurrent HCC after LR in China, the selection criteria are not well established. Methods: In this study, data from the China Liver Transplant Registry (CLTR) of 4,244 LT performed from January 2015 to December 2019 were examined, including 3,498 primary liver transplantation (PLT) and 746 SLT recipients. Propensity score matching (PSM) analysis was used to minimize between-group imbalances. The overall survival (OS) and disease-free survival (DFS) between PLT and SLT in recipients fulfilling the Milan or Hangzhou criteria were compared based on the multivariate analysis, nomograms were plotted to further classify the SLT group into low- and high-risk groups. Results: In this study, the 1-, 3- and 5-year OS and DFS of SLT recipients fulfilling Milan criteria (OS, P=0.01; DFS, P<0.001) or Hangzhou criteria (OS, P=0.03; DFS, P=0.003) were significantly reduced when compared to that of PLT group after PSM analysis. Independent risk factors, including preoperative transarterial chemoembolization (TACE), alpha fetoprotein (AFP) level, tumor maximum size and tumor total diameter were selected to draw a prognostic nomogram. The low-risk SLT recipients (1-year, 95.34%; 3-year, 84.26%; 5-year, 77.20%) showed a comparable OS with PLT recipients fulfilling Hangzhou criteria (P=0.107). Conclusions: An optimal nomogram model for prognosis stratification and clinical decision guidance of SLT was established. The low-risk SLT recipients based on the nomograms showed comparable survival with those fulfilling Hangzhou criteria in PLT group.
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The chaperonin TRiC/CCT is cytosolic cylindrical complex of 16 subunits encoded by eight essential genes CCT1-8. It contributes to folding 10% of cellular polypeptides in yeast. The strain carrying substitution point mutation G412E in the equatorial domain of Cct7p resulted in the improper folding of substrates. In this study, the Cct7p mutant exhibited sensitivity to non-optimal growth temperatures and cell wall stressors. Heat shock is known to disrupt cell wall and protein stability in budding yeast. Mitogen-activated protein kinase-mediated cell wall integrity pathway gets activated to compensate the perturbed cell wall. Overexpression of the PKC1 and SLT2 genes of MAPK signaling pathway in mutant rescued the growth and cell division defects. Additionally, the genes of the CWI pathway such as SED1, GFA1, PIR1, and RIM21 are down-regulated. The Cct7p mutant strain (G412E) is unable to withstand the heat stress due to the underlying defects in protein folding and cell wall maintenance. Taken together, our results strongly indicate the interaction between CCT and cell wall integrity pathway.
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Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Parede Celular/genética , Parede Celular/metabolismo , Resposta ao Choque Térmico/genéticaRESUMO
Topical glaucoma medications are effective and safe, but they have numerous well-documented limitations that diminish their long-term utility and sustainability. These limitations can include high rates of nonadherence (with associated glaucoma progression), concerning side effects, inconsistent circadian intraocular pressure (IOP) control, complex dosing regimens, difficulty with self-administration, costs, and decreased quality of life. Despite these limitations, topical medications traditionally have been first-line in the glaucoma treatment algorithm, as no other minimally invasive treatment alternatives existed. In recent years, however, novel interventional therapies-including sustained-release drug-delivery platforms, selective laser trabeculoplasty, and micro-invasive glaucoma surgery procedures-have made it possible to intervene earlier without relying on topical medications. As a result, the topical medication-first treatment approach is being reevaluated in an overall shift toward earlier more proactive interventions.
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Background: von Willebrand factors (vWFs), hemostatic factors, are produced as large multimers and are shear stress-dependently cleaved to become the appropriate size. A reduction in vWF large multimers develops in various conditions including the use of extracorporeal life support, which can cause excessive-high shear stress in the blood flow and result in hemostatic disorders. The objective of this prospective study was to investigate the impact of venovenous extracorporeal membrane oxygenation (VV ECMO) use on the status of vWF large multimers and hemostatic disorders during single lung transplantation (SLT). Methods: We prospectively enrolled 12 patients who underwent SLT at our center. Among them, seven patients were supported by VV ECMO intraoperatively (ECMO group) and the remaining five patients underwent SLT without ECMO support (control group). The vWF large multimer index (%) was defined as the ratio of the large multimer proportion in total vWF (vWF large multimer ratio) derived from a patient's plasma to that from standard human plasma. Results: The vWF large multimer index at the end of the surgery was significantly lower in the ECMO group than in the control group (112.6% vs. 75.8%, respectively; P<0.05). The intraoperative blood loss and the amounts of intraoperative transfusion products in the ECMO group tended to be greater than those in the control group; however, the differences were not significant. Conclusions: During SLT, the use of VV ECMO caused a decrease in the vWF large multimer index. The short duration of time of VV ECMO use in our study did not significantly affect the intra- and postoperative outcomes including blood loss, blood transfusion, and re-exploration thoracotomy for bleeding. Nevertheless, to comprehensively evaluate the actual influence of this decrease in the vWF large multimer index on intra- and postoperative outcomes, a multicenter larger-scale study is warranted.
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On 19 April 2022, in order to overcome a succession of recent global food health and agriculture safety (FHAS) incidents, the Taiwanese government instituted and announced 20 comprehensive Articles under the Taiwanese Food and Agricultural Education Law (TFAEL) for regulating the Taiwanese FHAS in order to completely construct the international strategies under the current global food security challenges of the FAHS. As a result, this research study firstly employs the learning community model (LCM) of the learning theory to measure the implementing depth of the international sustainability practice of the 20 Articles of the Taiwanese FHASE from a learning performance analytical perspective. Then, the social learning theory (SLT) of the educational theory is applied to consolidate the individual behaviors of the relative stakeholders, the organizational management of the relative industries and the socialized consent of the multilateral organization performance assessment network (MOPAN) of the Food and Agriculture Organization (FAO) of the United Nations (UN). After completing quantitative and qualitative analyses, the two most valuable conclusions and findings were as follows: (1) Not only Article 12, but also Articles 3, 4 and 5 of the new law can empirically facilitate strategic management for supporting and promoting the Taiwanese FHAS educational policy dialogue at a global, regional and country scale in order to effectively advance the international sustainable compatibility of the TFAEL. (2) Articles 6, 11 and 16 of the new law can completely construct operational management for building normative and standard-setting Taiwanese FHAS educational works in order to efficiently advance the international sustainable compatibility of the TFAEL. Therefore, beyond the analytical results of this research, the international sustainable compatibility of the TFAEL provides a direction for the development of sustainable food systems, food policies, agricultural food markets and food chains in order to overcome the various contemporary global food security challenges.
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BACKGROUND: Smokeless tobacco (SLT) use among women is widely prevalent in Manipur state accounting for 45% users as per Global Adult Tobacco Survey (GATS)-2 India. Studies from India and elsewhere indicate changes in the way people used SLT during COVID-19 lockdown. This study explores individual and economic influences on SLT consumption and cessation attempts by tribal women in Manipur during the first COVID-19 lockdown (March-June, 2020) in India. METHODS: Twenty in-depth interviews, both in-person and telephonically, were conducted among tribal women from Imphal west, Manipur, India, who used any SLT, from April to September 2020. Objective of the study was to understand the use, factors associated with consumption, purchasing behaviors, and cessation attempts of SLT during the lockdown. Thematic content analysis was used to identify core themes and codes. RESULTS: Study participants reported of changes in current SLT use during restrictions imposed to contain COVID-19 pandemic in India. Majority reported of reduction or quit attempts in SLT use. Reasons included inaccessibility due to travel restrictions, limited availability and price rise of SLT products, fear of COVID-19, and disposable income for purchase of SLT products. However, a few women reported of increased consumption due to bulk purchasing, or switching to other SLT products as a result of unavailability or price rise of preferred products or to cope up with social isolation caused by the lockdown. CONCLUSION: Study findings on factors influencing quit attempts and strategies used for reducing SLT use by tribal women in Imphal, Manipur provide valuable insights for development of appropriate intervention for prevention of SLT use among women.
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COVID-19 , Abandono do Uso de Tabaco , Tabaco sem Fumaça , Adulto , Humanos , Feminino , Pandemias , Índia/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças TransmissíveisRESUMO
Mitogen-activated protein kinase (MAPK) pathways regulate essential processes in eukaryotes. However, since uncontrolled activation of these cascades has deleterious effects, precise negative regulation of signaling flow through them, mainly executed by protein phosphatases, is crucial. Previous studies showed that the absence of Ptc1 protein phosphatase results in the upregulation of the MAPK of the cell wall integrity (CWI) pathway, Slt2, and numerous functional defects in Saccharomyces cerevisiae, including a failure to undergo cell separation under heat stress. In this study, we demonstrate that multibudded ptc1Δ cells also exhibit impaired mitochondrial inheritance and that excessive Slt2 kinase activity is responsible for their growth deficiency and daughter-specific G1 cell cycle arrest, as well as other physiological alterations, namely, mitochondrial hyperpolarization and reactive oxygen species (ROS) accumulation. We bring to light the fact that sustained Slt2 kinase activity inhibits signaling through the Sch9 branch of the TORC1 pathway in ptc1Δ cells, leading to increased autophagy. After cytokinesis, septin rings asymmetrically disassembled in ptc1Δ multibudded cells, abnormally remaining at the daughter cell side and eventually relocalizing at the daughter cell periphery, where they occasionally colocalized with the autophagic protein Atg9. Finally, we show that the inability of ptc1Δ cells to undergo cell separation is not due to a failure in the regulation of Ace2 and morphogenesis (RAM) pathway, since the transcription factor Ace2 correctly enters the daughter cell nuclei. However, the Ace2-regulated endochitinase Cts1 did not localize to the septum, preventing the proper degradation of this structure. IMPORTANCE This study provides further evidence that the cell cycle is regulated by complex signaling networks whose purpose is to guarantee a robust response to environmental threats. Using the S. cerevisiae eukaryotic model, we show that, under the stress conditions that activate the CWI MAPK pathway, the absence of the protein phosphatase Ptc1 renders Slt2 hyperactive, leading to numerous physiological alterations, including perturbed mitochondrial inheritance, oxidative stress, changes in septin dynamics, increased autophagy, TORC1-Sch9 inhibition, and ultimately cell cycle arrest and the failure of daughter cells to separate, likely due to the absence of key degradative enzymes at the septum. These results imply novel roles for the CWI pathway and unravel new cell cycle-regulatory controls that operate beyond the RAM pathway, arresting buds in G1 without compromising further division rounds in the mother cell.
Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Septinas/metabolismo , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Fosfoproteínas Fosfatases/farmacologia , Pontos de Checagem do Ciclo CelularRESUMO
OBJECTIVES: Aphasia is an acquired language-cognitive disorder that highly affects an individual's speech, language, and communication skills. Recovery from aphasia requires attentive treatment since it is a long and dynamic process. This study aimed to show interactive benefits of combining classical intervention strategies with new technological approaches and demonstrating their effectiveness. MATERIALS AND METHODS: A total of 40 individuals with Broca's aphasia were included in the study. The participants were divided into Application-1 Speech and Language Therapy, Application-2 Transcranial Magnetic Stimulation, Application-3 (consecutive Transcranial Magnetic Stimulation and Speech and Language Therapy), and Application-4 (Control Group) experimental groups, with 10 participants in each group. RESULTS: Analysis indicated that individuals in the group in which Transcranial Magnetic Stimulation and Speech and Language Therapy were applied consecutively had further increases in speech fluency, repetition, and naming scores from pre-test to post-test (p<0.01). Picture naming and quality-of-life communication scores of individuals in the group in which Speech and Language Therapy was performed increased further from pre-test to post-test (p<0.01). CONCLUSIONS: The results of the study showed a positive effect on language skills, naming scores, and participation in social life of Turkish-speaking aphasic individuals with the Speech and Language Therapy and Transcranial Magnetic Stimulation methods. The use of Transcranial Magnetic Stimulation alone is insufficient in this context. Although Speech and Language Therapy alone is effective in naming ability, Transcranial Magnetic Stimulation in addition to Speech and Language Therapy significantly increases the gain obtained with therapies.