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Three billion years of evolution has produced a tremendous diversity of protein molecules1, but the full potential of proteins is likely to be much greater. Accessing this potential has been challenging for both computation and experiments because the space of possible protein molecules is much larger than the space of those likely to have functions. Here we introduce Chroma, a generative model for proteins and protein complexes that can directly sample novel protein structures and sequences, and that can be conditioned to steer the generative process towards desired properties and functions. To enable this, we introduce a diffusion process that respects the conformational statistics of polymer ensembles, an efficient neural architecture for molecular systems that enables long-range reasoning with sub-quadratic scaling, layers for efficiently synthesizing three-dimensional structures of proteins from predicted inter-residue geometries and a general low-temperature sampling algorithm for diffusion models. Chroma achieves protein design as Bayesian inference under external constraints, which can involve symmetries, substructure, shape, semantics and even natural-language prompts. The experimental characterization of 310 proteins shows that sampling from Chroma results in proteins that are highly expressed, fold and have favourable biophysical properties. The crystal structures of two designed proteins exhibit atomistic agreement with Chroma samples (a backbone root-mean-square deviation of around 1.0 Å). With this unified approach to protein design, we hope to accelerate the programming of protein matter to benefit human health, materials science and synthetic biology.
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Algoritmos , Simulação por Computador , Conformação Proteica , Proteínas , Humanos , Teorema de Bayes , Evolução Molecular Direcionada , Aprendizado de Máquina , Modelos Moleculares , Dobramento de Proteína , Proteínas/química , Proteínas/metabolismo , Semântica , Biologia Sintética/métodos , Biologia Sintética/tendênciasRESUMO
There are diverse pathophysiological mechanisms involved in acute kidney injury (AKI). Among them, overactivity of the renin angiotensin system (RAS) has been described. Angiotensin converting enzyme 2 (ACE2) is a tissue RAS enzyme expressed in the apical border of proximal tubules. Given the important role of ACE2 in the metabolism of Angiotensin II this study was aimed to characterize kidney and urinary ACE2 in amouse model of AKI. Ischemia reperfusion injury (IRI) was induced in C57BL/6 mice by clamping of the left renal artery followed by removal of the right kidney. In kidneys harvested 48 hours after IRI, immunostaining revealed a striking maldistribution of ACE2 including spillage into the tubular lumen and presence of ACE2 positive luminal casts in the medulla. In cortical membranes ACE2 protein and enzymatic activity were both markedly reduced (37±4 vs. 100±6 ACE2/ß-Actin, P=0.0004 and 96±14 vs. 152±6 RFU/µg protein/h P=0.006). In urine, the full-length membrane bound ACE2 protein (100kD) was markedly increased (1120±405 vs. 100±46 ACE2/µg Crea, P=0.04) and casts stained for ACE2 were recovered in the urine sediment. In AKI caused by IRI there is a marked loss of ACE2 from the apical tubular border with deposition of ACE2 positive material in the medulla and increased urinary excretion of the full length-membrane bound ACE2 protein. The deficiency of tubular ACE2 in AKI suggests that provision of this enzyme could have therapeutic applications and that its excretion in the urine may also serve as a diagnostic marker of severe proximal tubular injury.
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Plant aquaporins (AQPs) facilitate the membrane diffusion of water and small solutes, including hydrogen peroxide (H2 O2 ) and, possibly, cations, essential signalling molecules in many physiological processes. While the determination of the channel activity generally depends on heterologous expression of AQPs in Xenopus oocytes or yeast cells, we established a genetic tool to determine whether they facilitate the diffusion of H2 O2 through the plasma membrane in living plant cells. We designed genetic constructs to co-express the fluorescent H2 O2 sensor HyPer and AQPs, with expression controlled by a heat shock-inducible promoter in Nicotiana tabacum BY-2 suspension cells. After induction of ZmPIP2;5 AQP expression, a HyPer signal was recorded when the cells were incubated with H2 O2 , suggesting that ZmPIP2;5 facilitates H2 O2 transmembrane diffusion; in contrast, the ZmPIP2;5W85A mutated protein was inactive as a water or H2 O2 channel. ZmPIP2;1, ZmPIP2;4 and AtPIP2;1 also facilitated H2 O2 diffusion. Incubation with abscisic acid and the elicitor flg22 peptide induced the intracellular H2 O2 accumulation in BY-2 cells expressing ZmPIP2;5. We also monitored cation channel activity of ZmPIP2;5 using a novel fluorescent photo-switchable Li+ sensor in BY-2 cells. BY-2 suspension cells engineered for inducible expression of AQPs as well as HyPer expression and the use of Li+ sensors constitute a powerful toolkit for evaluating the transport activity and the molecular determinants of PIPs in living plant cells.
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Aquaporinas , Peróxido de Hidrogênio , Peróxido de Hidrogênio/metabolismo , Células Vegetais/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Aquaporinas/genética , Aquaporinas/metabolismo , Membrana Celular/metabolismo , Cátions/metabolismo , Água/metabolismoRESUMO
The distinctive characteristics of near-infrared fluorescent organic molecules render them indispensable across diverse applications, from energy harvesting to bioimaging and sensing technologies. In this work, we continue our investigation on the chalcone derivative, 4-dimethylamino-2'-hydroxychalcone (nDHC, n = 1; where n is the number of olefinic bonds), by expanding the number of central double bonds (n = 2 (2DHC) and n = 3 (3DHC)). Additionally, we also synthesized the structurally related chalcones lacking the OH group (DC, 2DC, 3DC) in order to obtain a comprehensive understanding of their effects on the intramolecular charge transfer (ICT). The results show remarkable bathochromic shifts in absorption and fluorescence peaks in solution as n increases. These shifts, 20 nm and 35 nm for absorption and 100 nm and 200 nm for fluorescence in 2DHC and 3DHC, respectively, signify enhanced ICT and a significant increase in the excited state's dipole moment. The presence of OH groups notably amplifies these shifts due to additional electron donation, influencing solute-solvent interactions in solution. Femtosecond fluorescence upconversion and transient absoprtion techniques unraveled distinct dynamics in these derivatives, exhibiting the dominance of vibrational cooling, solvation, and intramolecular motions, particularly in the larger conjugated systems 3DHC and 3DC. The observed changes in the femtosecond transinet absorption spectra suggest the existence of new active states in extended conjugation systems, indicating diverse intramolecular conformational states contributing to their relaxation dynamics. The results of this study provide invaluable insights into excited-state spectroscopy, offering a roadmap for tailoring chalcone derivatives for specific applications.
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BACKGROUND: Despite the success of sleeve gastrectomy (SG) in of weight loss and treatment of the medical problems associated with obesity, some concerns have arisen about the need for revisional surgeries after SG in some patients. This study aimed to present an updated and comprehensive comparison among the presently available revisional surgeries employed explicitly in cases of inadequate outcomes after SG, which is the most frequently performed bariatric surgery in contemporary practice. METHODS: This network meta-analysis included studies that compared the outcomes of different revisional bariatric procedures after an inadequate outcome of SG. RESULTS: Searching across the electronic databases yielded 31 eligible articles. Re-SG was associated with the highest rate of significant complications. Patients treated with single anastomosis duodenal-ileal bypass (SADI) had a significantly higher percentage of total weight loss (%TWL) than those treated with one anastomosis gastric bypass (OAGB) and Roux-en-Y gastric bypass (RYGB). The percentage of excess weight loss (%EWL) at the end of the follow-up period was significantly higher in patients in the SADI group compared to those in the RYGB group and the OAGB, and re-SG exhibited the least values compared to SADI, biliopancreatic diversion with duodenal switch (BPD/DS), and OAGB. Significantly lower rates of reflux worsening/de novo development were observed in the SADI group compared to the OAGB group and the re-SG group, which showed significantly higher rates than SADI and RYGB. CONCLUSION: Our comprehensive network meta-analysis highlights SADI as a promising revisional option post-SG, demonstrating superior weight loss outcomes, lower significant complication rates, and a favorable impact on reflux compared to other procedures. While acknowledging the limitations of our study, these findings support the potential efficacy of SADI in addressing the challenges of inadequate weight loss after sleeve gastrectomy.
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BACKGROUND: Dromedaries' normal heart architecture and size have not been adequately examined utilizing magnetic resonance imaging (MRI) and topographic anatomy. RESULT: we aimed to investigate the regular appearance of the heart and its dimensions, using MRI and cross-sectional anatomy, in mature Arabian one-humped camels (Camelus dromedarius). We also analyzed hematological and cardiac biochemical markers. MRI scans were conducted on twelve camel heart cadavers using a closed 1.5-Tesla magnet with fast spin echo (FSE) weighted sequences. Subsequently, the hearts were cross-sectionally sliced. Additionally, hematobiochemical studies were conducted on ten mature live camels. The study analyzed standard cardiac dimensions including HL, BW, RA, LA, RV, LV, IVS, LAD, RAD, RVD, AoD, TCVD, and MVD. The results showed a strong positive correlation between the cardiac dimensions obtained from both gross analysis and MR images, with no significant difference between them. On both gross and MRI images, the usual structures of the heart were identified and labeled. Along with the cardiac markers (creatine kinase and troponin), the average hematological values and standard biochemical parameters were also described. CONCLUSION: According to what we know, this investigation demonstrates, for the first time the typical heart structures and dimensions of the heart in dromedaries, and it could serve as a basis for diagnosing cardiac disorders in these animals.
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Camelus , Coração , Imageamento por Ressonância Magnética , Animais , Camelus/anatomia & histologia , Imageamento por Ressonância Magnética/veterinária , Coração/anatomia & histologia , Coração/diagnóstico por imagem , Masculino , Feminino , Creatina Quinase/sangueRESUMO
BACKGROUND: The aim of this study was to assess the role of treatment of superficial venous reflux (SVR) in patients with combined deep segmental venous reflux as regards clinical symptoms as well as reflux improvement of the deep veins. METHODS: We reviewed 80 patients, retrospectively selected on the inclusion criteria and having combined SVR and segmental deep venous reflux who underwent SVR ablation. The contralateral limb of 44 patients was used as a control group, asked to wear compression stockings for 3 months during day time with no surgical intervention. Duplex ultrasounds follow-up was performed at 3, 6, and 12 months postoperatively. Clinical severity of venous disease was graded from C1 to C6 according to the CEAP (Clinical, Etiology, Anatomy, and Pathophysiology) classification. Duplex ultrasound was done in both supine and standing positions with non-weight-bearing of the examined limb. The venous reflux time, the venous flow volume and the peak venous flow velocity were registered. Removal of SVR was performed using either conventional surgery or radiofrequency ablation. The patient was required to wear compression stockings during the day time for the following weeks. RESULTS: During the follow-up period, all patients were improved clinically as regards pain, edema, and ulcer healing. All patients included in this study had no signs of residual SVR. Corrected deep venous segment reflux was in 36 (45%). Similar data at 3, 6, and 12 months postoperatively after SVR removal. The popliteal vein reflux responded less than the femoral vein reflux did. CONCLUSIONS: Treatment of the SVR eliminates segmental deep venous reflux in a good percentage of patients regardless of the treatment modality. Also, symptoms improvement and ulcer healing were documented, and hence, more studies are recommended to evaluate this role.
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Doenças Vasculares , Insuficiência Venosa , Humanos , Úlcera , Estudos Retrospectivos , Resultado do Tratamento , Veia Femoral/diagnóstico por imagem , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/cirurgia , Doença CrônicaRESUMO
PURPOSE: We aimed to evaluate the ability of the peripheral perfusion index (PPI) to predict reintubation of critically ill surgical patients. METHODS: This prospective observational study included mechanically ventilated adults who were extubated after a successful spontaneous breathing trial (SBT). The patients were followed up for the next 48 h for the need for reintubation. The heart rate, systolic blood pressure, respiratory rate, peripheral arterial oxygen saturation (SpO2), and PPI were measured before-, at the end of SBT, 1 and 2 h postextubation. The primary outcome was the ability of PPI 1 h postextubation to predict reintubation using area under the receiver operating characteristic curve (AUC) analysis. Univariate and multivariate analyses were performed to identify predictors for reintubation. RESULTS: Data from 62 patients were analysed. Reintubation occurred in 12/62 (19%) of the patients. Reintubated patients had higher heart rate and respiratory rate; and lower SpO2 and PPI than successfully weaned patients. The AUC (95%confidence interval) for the ability of PPI at 1 h postextubation to predict reintubation was 0.82 (0.71-0.91) with a negative predictive value of 97%, at a cutoff value of ≤ 2.5. Low PPI and high respiratory rate were the independent predictors for reintubation. CONCLUSION: PPI early after extubation is a useful tool for prediction of reintubation. Low PPI is an independent risk factor for reintubation. A PPI > 2.5, one hour after extubation can confirm successful extubation.
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Estado Terminal , Intubação Intratraqueal , Índice de Perfusão , Humanos , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Intubação Intratraqueal/métodos , Idoso , Extubação/métodos , Frequência Cardíaca/fisiologia , Saturação de Oxigênio/fisiologia , Respiração Artificial/métodos , Taxa Respiratória/fisiologia , Valor Preditivo dos Testes , AdultoRESUMO
BACKGROUND: The nutritional status and growth of children with Autism spectrum disorders (ASD) is influenced significantly by two factors; food selectivity behaviors due to their consumption of a limited variety of food and the high incidence of gastrointestinal (GIT) disorders. AIM: This study aimed to assess the nutritional adequacy and growth pattern of ASD children aged three to twelve years compared to their healthy developing peers. METHODS: A national comparative, facility-based cross-sectional study was conducted in eight Egyptian governorates on 285 Egyptian children diagnosed with ASD and 224 children who are their relatives as healthy developing peers. Anthropometric measurements were obtained, including weight, height, head circumference, and mid-upper arm circumference. Body Mass Index (BMI) was calculated and all numbers were plotted on WHO growth charts. Assessment of food preferences, and nutrient intake adequacy of children was done using the Food preference questionnaire, and the Dietary Reference Intakes (DRIs) of Egyptian children. RESULTS: Calorie-dense food and sugar intake were higher among ASD children than their healthy developing peers. ASD children omit some important protein sources such as dairy (COR = 5.2, 95% CI:2.7-9.9), meat, and poultry (COR = 2.7, 95% CI: 1.6-4.7), and a lower intake of fruits and vegetables than their healthy developing peers. For children with ASD in all age groups, a deficiency in the range of 50-60% was detected for vitamins (C, D, B6, thiamine, riboflavin, niacin) and minerals (iron). A deficiency in the range of 60-70% was detected for folate and calcium. A deficiency of vitamin C calcium and iron was also detected for both children with ASD and their healthy developing relatives aged 6 to 12 years. GIT disorders were common among ASD children compared to healthy developing peers (COR = 2.8 to 10.3). Children with ASD had four-fold higher odds of stunting (COR = 4.1, CI: 1.7-10.1), threefold higher odds of being overweight (COR = 3.3, CI: 1.48-7.32), and nearly eleven-fold higher odds of obesity (COR = 11.4, CI: 4.05-32.17) compared to their healthy developing peers. CONCLUSION: ASD children are prone to overweight and protein malnutrition. Their intake of fruits and vegetables is inadequate and hence their intake of vitamins and minerals is insufficient, contributing to stunting.
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Transtorno do Espectro Autista , Transtornos do Crescimento , Obesidade Infantil , Humanos , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/etiologia , Egito/epidemiologia , Masculino , Feminino , Estudos Transversais , Pré-Escolar , Criança , Obesidade Infantil/epidemiologia , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia , Estado Nutricional , Estudos de Casos e Controles , Preferências Alimentares , Índice de Massa Corporal , DietaRESUMO
OBJECTIVES: The aims of this study were to assess the impact of the closed-loop sampling method on blood loss and the need for blood transfusion in pediatric patients following cardiac surgery. DESIGN: Retrospective observational study. SETTING: A single tertiary center. PARTICIPANTS: All pediatric patients younger than 4 years old who were admitted to the pediatric intensive care unit (PICU) after cardiac surgery were enrolled. The study included 100 pediatric patients in the conservative (postimplementation) group and 43 pediatric patients in the nonconservative group (preimplementation). INTERVENTIONS: Observational. MEASUREMENTS: The primary outcome was the volume of blood loss during the PICU follow-up period. The secondary outcomes were the requirement for blood transfusion in each group, duration of mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, and mortality. MAIN RESULTS: In the conservative (postimplementation) group, blood loss during the follow-up period was 0.67 (0.33-1.16) mL/kg/d, while it was 0.95 (0.50-2.30) mL/kg/d in the nonconservative (preimplementation) group, demonstrating a significant reduction in blood loss in the conservative group (p = 0.012). The groups showed no significant differences in terms of the required blood transfusion volume postoperatively during the first 24 hours, first 48 hours, or after 48 hours (p = 0.061, 0.536, 0.442, respectively). The frequency of blood transfusion was comparable between the groups during the first 24 hours, first 48 hours, or after 48 hours postoperatively (p = 0.277, 0.639, 0.075, respectively). In addition, the groups did not show significant differences in the duration of mechanical ventilation, length of ICU stay, length of hospital stay, or mortality. CONCLUSIONS: The closed-loop sampling method can be efficient in decreasing blood loss during postoperative PICU follow-up for pediatric patients after cardiac surgeries. However, its application did not reduce the frequency or the volume of blood transfusion in these patients.
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OBJECTIVES: Investigating the impact of thermal and mechanical loading on the force generation of orthodontic aligners made from various thermoplastic materials and different compositions. MATERIALS AND METHODS: Five distinct materials were utilized including, three multi-layer (Zendura FLX, Zendura VIVA, CA Pro) and two single-layer (Zendura A and Duran). A total of 50 thermoformed aligners (n = 10) underwent a 48-hour ageing protocol, which involved mechanical loading resulting from a 0.2 mm facial malalignment of the upper right central incisor (Tooth 11) and thermal ageing through storage in warm distilled water at 37°C. The force exerted on Tooth 11 of a resin model was measured both before and after ageing using pressure-sensitive films and a biomechanical setup. RESULTS: Before ageing, pressure-sensitive films recorded normal contact forces ranging from 83.1 to 149.7 N, while the biomechanical setup measured resultant forces ranging from 0.1 to 0.5 N, with lingual forces exceeding facial forces. Multi-layer materials exhibited lower force magnitudes compared to single-layer materials. After ageing, a significant reduction in force was observed, with some materials experiencing up to a 50% decrease. Notably, multi-layer materials, especially Zendura VIVA, exhibited lower force decay. CONCLUSIONS: The force generated by aligners is influenced by both the aligner material and the direction of movement. Multi-layer materials exhibit superior performance compared to single-layer materials, primarily because of their lower initial force, which enhances patient comfort, and their capability to maintain consistent force application even after undergoing ageing.
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OBJECTIVES: To investigate the effects of material type and thickness on force generation and distribution by aligners. MATERIALS AND METHODS: Sixty aligners were divided into six groups (n = 10): one group with a thickness of 0.89 mm using Zendura Viva (Multi-layer), four groups with a thickness of 0.75 mm using Zendura FLX (Multi-layer), CA Pro (Multi-layer), Zendura (Single-layer), and Duran (Single-layer) sheets, and one group with a thickness of 0.50 mm using Duran sheets. Force measurements were conducted using Fuji® pressure-sensitive films. RESULTS: The lowest force values, both active and passive, were recorded for the multi-layered sheets: CA Pro (83.1 N, 50.5 N), Zendura FLX (88.9 N, 60.7 N), and Zendura Viva (92.5 N, 68.5 N). Conversely, the highest values were recorded for the single-layered sheets: Duran (131.9 N, 71.8 N) and Zendura (149.7 N, 89.8 N). The highest force was recorded at the middle third of the aligner, followed by the incisal third, and then the cervical third. The net force between the incisal and cervical thirds (FI-FC) showed insignificant difference across different materials. However, when comparing the incisal and middle thirds, the net force (FI-FM) was higher with single-layered materials. Both overall force and net force (FI-FM) were significantly higher with 0.75 mm compared to those with a thickness of 0.50 mm. CONCLUSIONS: Multi-layered aligner materials exert lower forces compared to their single-layered counterparts. Additionally, increased thickness in aligners results in enhanced retention and greater force generation. For effective bodily tooth movement, thicker and single-layered rigid materials are preferred. CLINICAL RELEVANCE: This research provides valuable insights into the biomechanics of orthodontic aligners, which could have significant clinical implications for orthodontists. Orthodontists might use this information to more effectively tailor aligner treatments, considering the specific tooth movement required for each individual patient. In light of these findings, an exchangeable protocol for aligner treatment is suggested, which however needs to be proven clinically. This protocol proposes alternating between multi-layered and single-layered materials within the same treatment phase. This strategy is suggested to optimize treatment outcomes, particularly when planning for a bodily tooth movement.
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Desenho de Aparelho Ortodôntico , Técnicas de Movimentação Dentária , Humanos , Fenômenos Biomecânicos , Resultado do Tratamento , Técnicas de Movimentação Dentária/métodosRESUMO
Bifenthrin (BF) is a broad-spectrum type I pyrethroid insecticide that acts on insects by impairing the nervous system and inhibiting ATPase activity, and it has toxic effects on non-target organisms and high persistence in the environment. This study aimed to determine the potential of six different fungi, including Pseudozyma hubeiensis PA, Trichoderma reesei PF, Trichoderma koningiopsis PD, Purpureocillium lilacinum ACE3, Talaromyces pinophilus ACE4, and Aspergillus niger AJ-F3, to degrade BF. Three different concentrations of BF, including 0.1%, 0.2%, and 0.3% w/v, were used in the sensitivity testing that revealed a significant (p ≤ 0.01) impact of BF on fungal growth. Enzymatic assays demonstrated that both intracellular and extracellular carboxylesterases hydrolyzed BF with the enzymatic activity of up to 175 ± 3 U (µmol/min) and 45 ± 1 U, respectively. All tested fungi were capable of utilizing BF as a sole carbon source producing 0.06 ± 0.01 to 0.45 ± 0.01 mg dry biomass per mg BF. Moreover, the presence of PytH was determined in the fungi using bioinformatics tools and was found in A. niger, T. pinophilus, T. reesei, and P. lilacinum. 3D structures of the PytH homologs were predicted using AlphaFold2, and their intermolecular interactions with pyrethroids were determined using MOE. All the homologs interacted with different pyrethroids with a binding energy of lesser than - 10 kcal/mol. Based on the study, it was concluded that the investigated fungi have a greater potential for the biodegradation of BF.
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PURPOSE: To study the effect of brimonidine on vascular density and flow index of optic nerve head (ONH) and macula in primary open angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). METHODS: Twenty-three brimonidine-naïve POAG patients were started on brimonidine. They underwent OCTA ONH and macula before commencing brimonidine and one month thereafter. Systemic arterial blood pressure (SABP) and intraocular pressure (IOP) were measured at each visit to calculate mean ocular perfusion pressure (MOPP). The OCT angiograms were analyzed using ImageJ software to calculate ONH and macular flow indices. RESULTS: Thirty-seven eyes (23 patients) with a mean age of 56.7 ± 12.49 years were included of whom 60.8% were males. Brimonidine was associated with an increase in the superficial flow index (SFI) (P-value = 0.02) and optic nerve head flow index (ONHFI) (P-value = 0.01). Also, superficial vascular density (SVD) for whole image, superior-hemi and fovea increased (P-value = 0.03, 0.02, 0.03 respectively). ONH inferior-hemi vascular density decreased (P-value = 0.01) despite an increase in inferior quadrant retinal nerve fiber layer thickness (RNFLT) (P-value = 0.03). There was no statistically significant correlation between flow indices and MOPP at baseline and follow-up. A moderate negative correlation was found between SVD and DVD at the fovea and MOPP at baseline and follow-up (P-value = 0.03, 0.05) (P-value = 0.02, 0.01) respectively. CONCLUSIONS: Brimonidine was associated with an increase in SFI, ONHFI and SVD indicating improved GCC and RNFL perfusion in POAG. Despite the increase in inferior quadrant RNFLT, the concomitant decrease in inferior-hemi ONHVD precluded a conclusion of hemodynamically-mediated improvement of RNFLT.
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Tartarato de Brimonidina , Angiofluoresceinografia , Glaucoma de Ângulo Aberto , Pressão Intraocular , Macula Lutea , Disco Óptico , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Glaucoma de Ângulo Aberto/fisiopatologia , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/diagnóstico , Masculino , Disco Óptico/irrigação sanguínea , Tartarato de Brimonidina/administração & dosagem , Tartarato de Brimonidina/farmacologia , Tartarato de Brimonidina/uso terapêutico , Pessoa de Meia-Idade , Feminino , Tomografia de Coerência Óptica/métodos , Macula Lutea/irrigação sanguínea , Macula Lutea/diagnóstico por imagem , Pressão Intraocular/fisiologia , Pressão Intraocular/efeitos dos fármacos , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/fisiopatologia , Vasos Retinianos/efeitos dos fármacos , Angiofluoresceinografia/métodos , Fluxo Sanguíneo Regional/fisiologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Idoso , Fundo de Olho , Estudos Prospectivos , Campos Visuais/fisiologia , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/efeitos dos fármacos , Anti-Hipertensivos/uso terapêutico , Fibras Nervosas/patologia , Fibras Nervosas/efeitos dos fármacos , Adulto , SeguimentosRESUMO
The use of nanotechnology has the potential to revolutionize the detection and treatment of cancer. Developments in protein engineering and materials science have led to the emergence of new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers for medicinal purposes have been approved for human trials, only a few have been authorized for clinical use in targeting cancer cells. In this review, we analyze some of the authorized formulations and discuss the challenges of translating findings from the lab to the clinic. This study highlights the various nanocarriers and compounds that can be used for selective tumor targeting and the inherent difficulties in cancer therapy. Nanotechnology provides a promising platform for improving cancer detection and treatment in the future, but further research is needed to overcome the current limitations in clinical translation.
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Nanopartículas , Neoplasias , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Nanotecnologia/métodos , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos , Composição de MedicamentosRESUMO
The realization of solar-light-driven CO2 reduction reactions (CO2 RR) is essential for the commercial development of renewable energy modules and the reduction of global CO2 emissions. Combining experimental measurements and theoretical calculations, to introduce boron dopants and nitrogen defects in graphitic carbon nitride (g-C3 N4 ), sodium borohydride is simply calcined with the mixture of g-C3 N4 (CN), followed by the introduction of ultrathin Co phthalocyanine through phosphate groups. By strengthening H-bonding interactions, the resultant CoPc/P-BNDCN nanocomposite showed excellent photocatalytic CO2 reduction activity, releasing 197.76 and 130.32 µmol h-1 g-1 CO and CH4 , respectively, and conveying an unprecedented 10-26-time improvement under visible-light irradiation. The substantial tuning is performed towards the conduction and valance band locations by B-dopants and N-defects to modulate the band structure for significantly accelerated CO2 RR. Through the use of ultrathin metal phthalocyanine assemblies that have a lot of single-atom sites, this work demonstrates a sustainable approach for achieving effective photocatalytic CO2 activation. More importantly, the excellent photoactivity is attributed to the fast charge separation via Z-scheme transfer mechanism formed by the universally facile strategy of dimension-matched ultrathin (≈4 nm) metal phthalocyanine-assisted nanocomposites.
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Diabetes mellitus is usually accompanied by nephropathy, retinopathy, and neuropathy as microvascular complications. MicroRNAs (miRNAs) can affect the kidney, retina, and peripheral neurons through their implication in pathways involved in angiogenesis, inflammation, apoptosis, as well as fibrosis within these tissues and hence, play a crucial role in the pathogenesis of microvascular complications. In this review, the updated knowledge of the role of miRNAs in the pathogenesis of diabetic microvascular complications was summarized. PubMed Central was searched extensively to retrieve data from a wide range of reputable biomedical reports/articles published after the year 2000 to systematically collect and present a review of the key molecular pathways mediating the hyperglycemia-induced adverse effects on vascular tissues, particularly in persons with T2DM. In the present review, miR-126, miR-29b, and miR-125a are implicated in diabetes-induced microvascular complications, while miR-146a is found to be connected to all these complications. Also, vascular endothelial growth factors are noted to be the most impacted targets by miRNAs in all diabetic microvascular problems.
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Diabetes Mellitus Tipo 2 , Retinopatia Diabética , MicroRNAs , Humanos , MicroRNAs/genética , Retinopatia Diabética/genética , Retinopatia Diabética/complicações , Retinopatia Diabética/patologia , Retina/patologia , Inflamação/genética , Inflamação/complicações , Rim , Diabetes Mellitus Tipo 2/complicaçõesRESUMO
Growing antimicrobial resistance (AMR) is a threat to human and animal populations citing the limited available options. Alternative antimicrobial options or functional enhancement of currently available antimicrobials remains only options. One of the potential options seems stem cells especially the mesenchymal stem cells (MSCs) that show antimicrobial properties. These cells additionally have pro-healing effects that may plausibly improve healing outcomes. MSCs antimicrobial actions are mediated either through direct cell-cell contact or their secretome that enhances innate immune mediated antimicrobial activities. These cells synergistically enhance efficacy of currently available antimicrobials especially against the biofilms. Reciprocal action from antimicrobials on the MSCs functionality remains poorly understood. Currently, the main limitation with MSCs based therapy is their limited efficacy. This demands further understanding and can be enhanced through biotechnological interventions. One of the interventional options is the 'priming' to enhance MSCs resistance and specific expression potential. The available literature shows potential antimicrobial actions of MSCs both ex vivo as well as in vivo. The studies on veterinary species are very promising although limited by number and extensiveness in details for their utility as standard therapeutic agents. The current review aims to discuss the role of animals in AMR and the potential antimicrobial actions of MSCs in veterinary medicine. The review also discusses the limitations in their utilization as standard therapeutics.
Assuntos
Infecções Bacterianas , Terapia Baseada em Transplante de Células e Tecidos , Células-Tronco Mesenquimais , Animais , Animais Domésticos , Infecções Bacterianas/terapia , Infecções Bacterianas/veterinária , Terapia Baseada em Transplante de Células e Tecidos/veterinária , Resistência a Medicamentos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Moléculas com Motivos Associados a Patógenos/metabolismo , Viroses/terapia , Viroses/veterinária , Secretoma , Peptídeos Antimicrobianos/metabolismoRESUMO
BACKGROUND: Limited data exists on herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections in migrant populations. This study investigated HSV-1 and HSV-2 seroprevalences and associations among craft and manual workers (CMWs) in Qatar who constitute 60% of Qatar's population. METHODS: A national population-based cross-sectional seroprevalence survey was conducted on the CMW population, all men, between July 26 and September 9, 2020. 2,612 sera were tested for anti-HSV-1 IgG antibodies using HerpeSelect 1 ELISA IgG kits and for anti-HSV-2 IgG antibodies using HerpeSelect 2 ELISA IgG kits (Focus Diagnostics, USA). Univariable and multivariable logistic regression analyses were conducted to identify associations with HSV-1 and HSV-2 infections. RESULTS: Serological testing identified 2,171 sera as positive, 403 as negative, and 38 as equivocal for HSV-1 antibodies, and 300 sera as positive, 2,250 as negative, and 62 as equivocal for HSV-2 antibodies. HSV-1 and HSV-2 seroprevalences among CMWs were estimated at 84.2% (95% CI 82.8-85.6%) and 11.4% (95% CI 10.1-12.6%), respectively. HSV-1 infection was associated with nationality, educational attainment, and occupation. HSV-2 infection was associated with age, nationality, and educational attainment. CONCLUSIONS: Over 80% of CMWs are infected with HSV-1 and over 10% are infected with HSV-2. The findings highlight the need for sexual health programs to tackle sexually transmitted infections among the CMW population.
Assuntos
Herpes Simples , Herpesvirus Humano 1 , Migrantes , Masculino , Humanos , Catar/epidemiologia , Estudos Transversais , Estudos Soroepidemiológicos , Herpes Simples/epidemiologia , Herpesvirus Humano 2 , Anticorpos Antivirais , Imunoglobulina GRESUMO
Catalytic oxidation is considered a highly effective method for the elimination of volatile organic compounds. Oxygen vacancy defect engineering in a catalyst is considered an effective approach for high-performance catalysts. Herein, a series of doped MnxCe1-xO2 catalysts (x = 0.05-0.2) with oxygen vacancy defects were synthesized by doping low-valent Mn in a CeO2 lattice. Different characterization techniques were utilized to inspect the effect of doping on oxygen vacancy defect generation. The characterization results revealed that the Mn0.15Ce0.85O2 catalyst has the maximum oxygen vacancy concentration, leading to increased active oxygen species and enhanced oxygen mobility. Thus, Mn0.15Ce0.85O2 catalyst showed an excellent toluene oxidation activity with 90% toluene conversion temperature (T90) of 197 °C at a weight hourly space velocity of 40,000 mL g-1 h-1 as compared to undoped CeO2 (T90 = 225 °C) and Ce based oxides in previous reports. In addition, the Mn0.15Ce0.85O2 catalyst displayed strong recyclability, water resistant ability and long-time stability. The in situ DRIFT results showed that the Mn0.15Ce0.85O2 catalyst has a robust oxidation capability as toluene is quickly adsorbed and actuated as compared to CeO2. Thus, the present work lays the foundation for designing a highly active catalyst for toluene elimination from the environment.