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To evaluate EEG monitoring during neonatal ECMO and to identify any correlations between seizure detection to abnormal neuroimaging. Eight-year, service evaluation of neonates who received at least one continuous EEG (cEEG) whilst on ECMO at Great Ormond Street Hospital. Pearson's chi-square test and multivariate logistic regression analysis were used to assess clinical and EEG variables association with seizures and neuroimaging findings. Fifty-seven neonates were studied; 57 cEEG recordings were reviewed. The incidence of seizures was 33% (19/57); of these 74% (14/19) were electrographic-only. The incidence of status epilepticus was 42%, (8/19 with 6 neonates having electrographic-only status and 2 electro-clinical status. Seizures were detected within an hour of recording in 84%, (16/19). The overall mortality rate was 39% (22/57). Seizure detection was strongly associated with female gender (OR 4.8, 95% CI: 1.1-20.4, p = 0.03), abnormal EEG background activity (OR 2.8, 95% CI: 1.1-7.4, p = 0.03) and abnormal EEG focal features (OR 23.6, 95% CI: 5.4-103.9, p = 0.001). There was a strong association between the presence of seizures and abnormal neuroimaging findings (OR 10.9, 95% CI: 2.8-41.9, p = 0.001). Neonates were highly likely to have abnormal neuroimaging findings in the presence of severely abnormal background EEG (OR 9.5, 95% CI 1.7-52.02, p = 0.01) and focal EEG abnormalities (OR 6.35, 95% CI 1.97-20.5, p = 0.002)Conclusion: The study highlights the importance of cEEG in neonates undergoing ECMO. An association between seizure detection and abnormal neuroimaging findings was described. What is Known: ⢠Patients on ECMO are at a higher risk of seiures. ⢠Continuous EEG monitoring is recommended by the ACNS for high risk and ECMO patients. What is New: ⢠In this cohort, neonates with sezirues were 11 times more likely of having abnromal neuroimaging findings. ⢠Neonates with burst suppressed or suppressed EEG background were 9.5 times more likely to have abnormal neuroimaging findings. What does this study add? ⢠This study reports a 33% incidence of neonatal seizures during ECMO. ⢠Neonates with seizures were 11 times more likely to have an abnormal brain scan. ⢠The study captures the real-time approach of EEG monitoring. ⢠Recommended cEEG monitoring should last at least 24 h for ECMO patients. ⢠This is the first study to assess this in neonates only.
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Eletroencefalografia , Oxigenação por Membrana Extracorpórea , Convulsões , Humanos , Masculino , Recém-Nascido , Feminino , Eletroencefalografia/métodos , Convulsões/etiologia , Convulsões/diagnóstico , Estudos Retrospectivos , Incidência , Estado Epiléptico/etiologia , Estado Epiléptico/diagnóstico , Neuroimagem/métodos , Modelos LogísticosRESUMO
OBJECTIVE: Compare the effectiveness of palatoplasty and pharyngoplasty procedures at resolving hypernasality in patients with 22q11.2 deletion syndrome (22q). DESIGN: Retrospective cohort study. SETTING: Metropolitan children's hospital. PATIENTS: Fourteen patients with 22q presenting for management of velopharyngeal insufficiency. INTERVENTIONS: Palatoplasty or pharyngoplasty procedure. MAIN OUTCOME MEASURE: Resolution of hypernasality 12 months postoperatively. RESULTS: Both procedure groups had a mean preoperative velopharyngeal gap of 6.2â mm during phonation. No patient who underwent palatoplasty achieved resolution of hypernasality; 1/7 patients had worse hypernasality, 4/7 had no change, and 2/7 had improved hypernasality. In contrast, hypernasality was resolved in 6/7 patients in the pharyngoplasty group, which was significantly (P = .03) higher than the palatoplasty group. CONCLUSIONS: In patients with 22q, palatoplasty procedures may be less effective than pharyngoplasty procedures at resolving hypernasality. This may be due to underlying anatomic or physiologic differences, such as increased pharyngeal depth and hypodynamic muscles.
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OBJECTIVE: To investigate whether flexible nasopharyngoscopy, when performed in addition to magnetic resonance imaging (MRI), influences the type of surgery selected or success of surgery in patients with velopharyngeal insufficiency (VPI). DESIGN: Cohort study. SETTING: A metropolitan children's hospital. PATIENTS: Patients with non-syndromic, repaired cleft palate presenting for management of VPI. INTERVENTIONS: MRI and nasopharyngoscopy or MRI alone for preoperative imaging of the velopharyngeal mechanism. MAIN OUTCOME MEASURES: (1) Surgical selection and (2) resolution of hypernasality. All speech, MRI, and nasopharyngoscopy measurements were performed by raters blinded to patients' medical and surgical history. RESULTS: Of the 25 patients referred for nasopharyngoscopy, 76% completed the exam. Of the 41 patients referred for MRI, the scan was successfully completed by 98% of patients. Completion of nasopharyngoscopy was significantly (p=0.01) lower than MRI. Surgical selection did not significantly differ (p=0.73) between the group receiving MRI and nasopharyngoscopy and the group receiving MRI alone, nor was there a significant difference between these groups in the proportion of patients achieving resolution of hypernasality postoperatively (p=0.63). Percent total velopharyngeal closure assessments on nasopharyngoscopy and MRI were strongly correlated (r=0.73). CONCLUSIONS: In patients receiving MRI as part of their preoperative VPI evaluation, the addition of nasopharyngoscopy did not result in a difference in surgical selection or resolution of hypernasality. Routine inclusion of nasopharyngoscopy may not be necessary for the evaluation of velopharyngeal anatomy when MRI is available.
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INTRODUCTION: The levator veli palatini (LVP) muscle has two segments with distinct roles in velopharyngeal function. Previous research suggests longer extravelar segments with shorter intravelar segments may lead to a more advantageous mechanism for velopharyngeal closure. The purpose of this study was to examine whether the distribution of the LVP intravelar and extravelar segments differs between children with cleft palate with and without VPI and controls. METHODS: The study included 97 children: 37 with cleft palate +/- lip with VPI, 37 controls, and 19 with cleft palate with normal resonance. Measures included mean LVP length, mean extravelar LVP length, and intravelar LVP length. RESULTS: Overall mean LVP length was similar (P = .267) between controls and children with cleft palate (with and without VPI). However, there was a significant difference (P < .001) between group for both intravelar and extravelar LVP lengths: the intravelar segment was significantly longer in those with VPI compared to controls and children with cleft palate and normal resonance; and the extravelar segment was significantly shorter in those with VPI compared to controls and children with cleft palate and normal resonance. CONCLUSIONS: Results from this study demonstrate a significant difference between the distribution of the functional segments of the LVP among children with VPI, with a more disadvantageous distribution of the muscle segments among those with VPI.
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BACKGROUND & AIMS: Artificial intelligence (AI) may detect colorectal polyps that have been missed due to perceptual pitfalls. By reducing such miss rate, AI may increase the detection of colorectal neoplasia leading to a higher degree of colorectal cancer (CRC) prevention. METHODS: Patients undergoing CRC screening or surveillance were enrolled in 8 centers (Italy, UK, US), and randomized (1:1) to undergo 2 same-day, back-to-back colonoscopies with or without AI (deep learning computer aided diagnosis endoscopy) in 2 different arms, namely AI followed by colonoscopy without AI or vice-versa. Adenoma miss rate (AMR) was calculated as the number of histologically verified lesions detected at second colonoscopy divided by the total number of lesions detected at first and second colonoscopy. Mean number of lesions detected in the second colonoscopy and proportion of false negative subjects (no lesion at first colonoscopy and at least 1 at second) were calculated. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted by endoscopist, age, sex, and indication for colonoscopy. Adverse events were also measured. RESULTS: A total of 230 subjects (116 AI first, 114 standard colonoscopy first) were included in the study analysis. AMR was 15.5% (38 of 246) and 32.4% (80 of 247) in the arm with AI and non-AI colonoscopy first, respectively (adjusted OR, 0.38; 95% CI, 0.23-0.62). In detail, AMR was lower for AI first for the ≤5 mm (15.9% vs 35.8%; OR, 0.34; 95% CI, 0.21-0.55) and nonpolypoid lesions (16.8% vs 45.8%; OR, 0.24; 95% CI, 0.13-0.43), and it was lower both in the proximal (18.3% vs 32.5%; OR, 0.46; 95% CI, 0.26-0.78) and distal colon (10.8% vs 32.1%; OR, 0.25; 95% CI, 0.11-0.57). Mean number of adenomas at second colonoscopy was lower in the AI-first group as compared with non-AI colonoscopy first (0.33 ± 0.63 vs 0.70 ± 0.97, P < .001). False negative rates were 6.8% (3 of 44 patients) and 29.6% (13 of 44) in the AI and non-AI first arms, respectively (OR, 0.17; 95% CI, 0.05-0.67). No difference in the rate of adverse events was found between the 2 groups. CONCLUSIONS: AI resulted in an approximately 2-fold reduction in miss rate of colorectal neoplasia, supporting AI-benefit in reducing perceptual errors for small and subtle lesions at standard colonoscopy. CLINICALTRIALS: gov, Number: NCT03954548.
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Adenoma , Pólipos do Colo , Neoplasias Colorretais , Adenoma/diagnóstico por imagem , Adenoma/patologia , Inteligência Artificial , Pólipos do Colo/diagnóstico por imagem , Pólipos do Colo/patologia , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/métodos , HumanosRESUMO
The objective of the present investigation was to prepare and optimize lyophilized mixed micelles (Lyp-EXE-MMs) of exemestane (EXE) with improved solubility, bioavailability, in vivo anticancer activity, and physical stability, by using various cryoprotectants. The prepared lyophilized mixed micelles were characterized by various techniques, including dynamic light scattering, zeta potential, powdered X-ray diffraction, differential scanning calorimetry (DSC), nuclear magnetic resonance (1 H NMR), transmission electron microscopy (TEM), and so on. Thereafter, the lyophilized micelles were evaluated for ex vivo permeation, in vitro drug release and gene/protein expression (RT-PCR and Western blot analysis) in MCF-7 breast cancer cells. The developed formulation was also investigated for its in vivo anticancer study in BALB/c mice with induced breast cancer. The use of trehalose (10% w/w) was proven to be a suitable cryoprotectant for these micelles. Lyp-EXE-MMs were spherical, with a particle size of 42.9 ± 3.8 nm and a polydispersity index of 0.307 ± 0.122. Furthermore, % drug loading and % entrapment efficiency were found to be 5.8 ± 1.4 and 89.1 ± 1.1, respectively. Lyp-EXE-MMs showed sustained release behavior as compared to EXE-suspensions in SGF/SIF (pH 1.2 and 6.8) and phosphate buffer saline (pH 7.4). The micelles induced apoptosis through the regulation of BAX, BCL2, Caspase-3, p53, and CYP19A1 in MCF-7 cells, which was correlated to enhanced ex vivo drug permeation. Animals receiving EXE micelle formulations showed reduced tumor volume and improved survivability and pharmacokinetic parameters as compared to pure EXE. Lyp-EXE-MMs were found to withstand simulated harsh conditions of SGF/SIF during stability studies. The fabricated EXE micellar preparations hold a promising approach for breast cancer treatment.
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Androstadienos , Micelas , Animais , Camundongos , Relação Estrutura-Atividade , Solubilidade , Androstadienos/química , Androstadienos/farmacocinética , Portadores de Fármacos/químicaRESUMO
Frontal orbital advancement (FOA) is frequently performed for patients with syndromic and/or multisuture craniosynostosis. A small proportion of patients who undergo FOA have unfavorable growth and subsequently require a second FOA later in life; however, the perioperative risks associated with this second procedure are not well studied. We report results from a retrospective review of FOAs conducted from 2007 to 2022 at a single site with the same craniofacial surgeon. A total of 33 patients were included. Perioperative outcomes were compared between primary and secondary FOA procedures. The two groups were similar in regard to suture involvement and diagnosis, although the secondary FOA group was older at the time of their FOA (1.23 versus 7.07 y, P <0.001). There was no significant difference between groups in operating time, volume of blood transfusion by weight, or in the incidence of postoperative wound complications ( P >0.05). Primary FOA procedures had significantly higher weight-adjusted blood loss (28 versus 18 mL/kg, P =0.014), with a higher proportion of patients receiving a blood transfusion (95% versus 62%, P =0.025). There was no significant difference between groups in the incidence of intraoperative dural injury (50% versus 84%, P =0.067). Our findings suggest that secondary procedures appear to impose less of a surgical risk relative to primary FOA traditionally performed in infancy, likely because of the advanced age at the time of secondary FOA.
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Craniossinostoses , Humanos , Lactente , Craniossinostoses/cirurgia , Craniossinostoses/complicações , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Morbidade , Transfusão de Sangue , Estudos RetrospectivosRESUMO
OBJECTIVE: To predict the morbidity of sagittal suturectomy using preoperative computer tomographic measurement of frontal and parietal bone thickness in osteotomy sites. DESIGN: Retrospective analysis. SETTING: Tertiary children's hospital. PATIENTS: Fifty infants with nonsyndromic, isolated sagittal craniosynostosis who underwent extended sagittal suturectomy from 2015-2022. METHODS: Mean thickness of the frontal and parietal bone in regions of osteotomies were determined for each patient from preoperative CT images obtained within 30 days prior to suturectomy. The relationship between bone thickness (mm) and estimated blood loss (mL) was evaluated using Spearman's correlation and a multivariable model that adjusted for patient weight and surgery duration. The association between bone thickness and perioperative blood transfusion was evaluated using a multivariable logistic model controlling for patient weight and surgery duration. MAIN OUTCOME MEASURES: Estimated blood loss, perioperative blood transfusion. RESULTS: Frontal and parietal bone thickness in the region of osteotomies were positively correlated with estimated blood loss (p < 0.01). After adjusting for patient weight and duration of operation, both parietal and frontal bone thickness were associated with intraoperative blood loss (R2 = 0.292, p = 0.002 and R2 = 0.216, p = 0.026). Thicker frontal and parietal bone in the line of osteotomies resulted in significantly higher odds of blood transfusion. Bone thickness in the line of parietal osteotomies was 76% accurate at identifying patients who would require blood transfusion (p = 0.004). CONCLUSIONS: Frontal and parietal bone thickness in the line of osteotomies is associated with blood loss and perioperative blood transfusion for sagittal suturectomy operations.
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BACKGROUND: Patients undergoing orthognathic surgery may have limited information surrounding surgery. This leads to less satisfaction with surgical outcomes, anxiety surrounding surgery and difficulty following perioperative instructions. SOLUTION: Providing a multi-disciplinary pre-operative educational experience for patients and caregivers improves surgical readiness and satisfaction. WHAT IS NEW: Our team provides a "Jaw Surgery Workshop" which includes lectures from providers, previous patients, cookbooks and supplies. This allows for improved confidence and expectations surrounding jaw surgery.
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BACKGROUND: The objective of this randomized trial was to evaluate the short-term effect of bilingual written and interpersonal education regarding mammographic breast density (MBD). METHODS: Latinas aged 40 to 74 years who were presenting for screening mammography were recruited and randomized 1:1:1 to receive a letter with their mammogram and MBD results (usual care [UC]), a letter plus a brochure (enhanced care [ENH]), or a letter plus a brochure and telephonic promotora education (interpersonal care [INT]). Surveys were administered at enrollment (T0 ) and 2 weeks to 6 months after intervention delivery (T1 ). Differences were assessed with χ2 , Kruskal-Wallis, and McNemar tests and pairwise comparisons as appropriate. INT metrics and audio recordings were analyzed with descriptive statistics and qualitative content analysis. RESULTS: Between October 2016 and October 2019, 943 of 1108 Latina participants (85%) completed both surveys. At T1 , INT participants were more likely (P < .001) to report seeing their MBD results in the letter (70.2%) than UC (53.1%) or ENH participants (55.1%). The percentage of INT women who reported speaking with a provider about MBD (29.0%) was significantly greater (P < .001) than the percentage of UC (14.7%) or ENH participants (15.6%). All groups saw significant (P < .001) but nondifferential improvements in their knowledge of MBD as a masking and risk factor. In the INT group, the promotora delivered education to 77.1% of the 446 participants randomized to INT and answered questions at 28.3% of the encounters for an average of $4.70 per participant. CONCLUSIONS: Among Latinas in a low-resource setting, MBD knowledge may increase with written or interpersonal education, but with modest investment, interpersonal education may better improve MBD awareness and prompt patient-provider discussions.
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Densidade da Mama , Neoplasias da Mama , Adulto , Idoso , Detecção Precoce de Câncer , Feminino , Hispânico ou Latino , Humanos , Mamografia , Pessoa de Meia-IdadeRESUMO
A library of 49 analogs of imidazo[1,2-a]pyridine with 2-halo, aryl, styryl and phenylethynyl-substitution at C-2 position and N-/O-/S-methyl linkage at C-3 position, have been synthesized and evaluated for their anti-proliferative activity against breast (MCF-7, MDA-MB-231), pancreatic (MiaPaca-2), lung (A549), prostate (PC-3) and colon (HCT-116) cancer cell lines and normal cells (HEK-293). Among the screened compounds, 5b exhibited best anticancer potential in all tested cancer cells with IC50 ranging from 3.5 to 61.1 µM and no toxicity in normal cells. Further, mechanistic study of 5b revealed concentration dependent increased generation of ROS, reduced mitochondrial membrane potential (MMP), surface and nuclear morphological alterations and inhibition of colony formation in HCT-116 cells. Western blot results had shown that the cell death in HCT-116 colon cancer cells was achieved through the induction of apoptosis via upregulation of the PTEN gene and downregulation of AKT pathway. Similarly, 5b treatment induced caspase-3 cleavage which is a hallmark of apoptosis. Molecular docking and binding energy (ΔG) studies of hit 5b with respect to three important cancer targets (EGFR, mTOR and PI3Kα) revealed strong binding of inhibitor with PI3Kα (docking score -6.932 and ΔG -56.297).
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Antineoplásicos , Antineoplásicos/química , Apoptose , Caspase 3 , Linhagem Celular Tumoral , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Células HEK293 , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Piridinas/farmacologia , Relação Estrutura-AtividadeRESUMO
In the present work we synthesize nickel oxide nanoparticles (NiO NPs) using Rhododendron arboretum (flower) (RNi), Tinospora cordifolia (stems) (GNi), Corylus jacquemontii (seeds) (CNi), and Nardostachys jatamansi (roots) (NNi) extracts by co-precipitation method. The synthesized NiO NPs were characterized in detail in terms of their morphological, crystalline nature, structural and antiproliferative activity against rat skeletal myoblast (L-6) cell lines. Morphological studies confirmed the formation of nanoparticles, while the structural and compositional characterization revealed the well-crystallinity and high purity of the synthesized nanoparticles. For biological applications and cytotoxicity examinations of the synthesized NPs, the rat skeletal myoblast (L-6) cell lines were subjected to study. By detailed cytotoxic investigations, it was observed that among the four kinds of NiO NPs prepared through different plant extracts, the Tinospora cordifolia (stems) showed strong antiproliferative activity against rat skeletal myoblast (L-6) cell lines and the calculated IC50 was 1.671 mg/mL. The observed antiproliferative activity towards different NiO NPs were in the order of GNi > NNi > RNi > CNi. The present studies demonstrate that simply synthesized NiO can efficiently be used as antiproliferative agents.
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Antineoplásicos , Nanopartículas Metálicas , Nanopartículas , Animais , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Níquel/metabolismo , Níquel/toxicidade , Extratos Vegetais/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Microbial endophytes are ubiquitous and exist in each recognised plant species reported till date. Within the host plant, the entire community of microbes lives non-invasively within the active internal tissues without causing any harm to the plant. Endophytes interact with their host plant via metabolic communication enables them to generate signal molecules. In addition, the host plant's genetic recombination with endophytes helps them to imitate the host's physicochemical functions and develop identical active molecules. Therefore, when cultured separately, they begin producing the host plant phytochemicals. The fungal species Penicillium chrysogenum has portrayed the glory days of antibiotics with the invention of the antibiotic penicillin. Therefore, fungi have substantially supported social health by developing many bioactive molecules utilised as antioxidant, antibacterial, antiviral, immunomodulatory and anticancerous agents. But plant-related microbes have emanated as fountainheads of biologically functional compounds with higher levels of medicinal perspective in recent years. Researchers have been motivated by the endless need for potent drugs to investigate alternate ways to find new endophytes and bioactive molecules, which tend to be a probable aim for drug discovery. The current research trends with these promising endophytic organisms are reviewed in this review paper. KEY POINTS: ⢠Identified 54 important bioactive compounds as agricultural relevance ⢠Role of genome mining of endophytes and "Multi-Omics" tools in sustainable agriculture ⢠A thorough description and graphical presentation of agricultural significance of plant endophytes.
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Endófitos , Plantas , Agricultura , Antibacterianos , Segurança Alimentar , Fungos , Compostos FitoquímicosRESUMO
Enzymes are one of the most significant products produced primarily from microbial sources for human requirements. The purpose of this work was to isolate, screen, and optimize enzyme production under solid-state fermentation. In the present study, amylase-producing bacteria were isolated from the local region of Ambala. A total of six samples were taken, out of which 14 isolates were isolated, among which seven isolates were found to be amylase producing. Highest amylase yield was obtained from isolate A11, further studied for the production of amylase under solid substrate fermentation (SSF), and also optimized the conditions for increased production of amylase. The molecular and biochemical characterization confirmed it as a strain of Alkalihalobacillus clausii. It was observed that growth parameters showed a profound effect on the production. The bacterium produces ample amount (7.3 × 103 IU/g) of alpha amylase using wheat bran using OVAT (one variable at a time) approach. Further using RSM (Response Surface Methodology) resulted in 3.78-fold increase in alpha amylase production, i.e., 27.57 × 103 IU/g.
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Amilases , alfa-Amilases , Humanos , Fermentação , Fibras na Dieta , Bactérias/genéticaRESUMO
Microalgae are a potential source of a wide range of food and novel value-added products. The versatility of microalgae to produce different kind of pigments is gaining interest as a sustainable source of natural carotenoids. Currently, commercial production of carotenoids from selected microalgae requires special culture conditions which are difficult to maintain. The present study has been undertaken to optimize culture conditions for growth and carotenoid production by a new isolate Scenedesmus quadricauda PUMCC 4.1.40. The results revealed that test organism produced 1.54 mg dry biomass/ml with a content of 40 µg carotenoids/mg dry biomass during stationary phase. The growth and carotenoid production was increased by 2.4-fold under combined optimized culture conditions. The optimized conditions were growth medium, Chu-10; pH 8.5; temperature, 30°C; nitrogen, 20 mM nitrate; phosphate, 0.22 mM; NaCl, 0.42 mM and blue light. Separation and identification of four important carotenoids through high-performance thin-layer chromatography (HPTLC) followed by purification using flash chromatography and quantification by HPLC revealed 23.8, 19.0, 6.5, and 4.0 µg astaxanthin, ß-carotene, lutein, and canthaxanthin /mg dry biomass, respectively. The amount of total carotenoids (98 µg/mg dry biomass) containing 40% valuable astaxanthin and ß-carotene produced under optimized conditions was significantly higher than control cultures. This justifies that S. quadricauda is a promising candidate for scale-up production of carotenoid.
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Microalgas , Scenedesmus , Biomassa , Carotenoides/química , beta CarotenoRESUMO
Leaf rust, caused by Puccinia hordei, is a devastating fungal disease affecting barley (Hordeum vulgare subsp. vulgare) production globally. Despite the effectiveness of genetic resistance, the deployment of single genes often compromises durability due to the emergence of virulent P. hordei races, prompting the search for new sources of resistance. Here we report on the cloning of Rph15, a resistance gene derived from barley's wild progenitor H. vulgare subsp. spontaneum. We demonstrate using introgression mapping, mutation and complementation that the Rph15 gene from the near-isogenic line (NIL) Bowman + Rph15 (referred to as BW719) encodes a coiled-coil nucleotide-binding leucine-rich repeat (NLR) protein with an integrated Zinc finger BED (ZF-BED) domain. A predicted KASP marker was developed and validated across a collection of Australian cultivars and a series of introgression lines in the Bowman background known to carry the Rph15 resistance. Rph16 from HS-680, another wild barley derived leaf rust resistance gene, was previously mapped to the same genomic region on chromosome 2H and was assumed to be allelic with Rph15 based on genetic studies. Both sequence analysis, race specificity and the identification of a knockout mutant in the HS-680 background suggest that Rph15- and Rph16-mediated resistances are in fact the same and not allelic as previously thought. The cloning of Rph15 now permits efficient gene deployment and the production of resistance gene cassettes for sustained leaf rust control.
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Basidiomycota , Hordeum , Austrália , Basidiomycota/genética , Mapeamento Cromossômico , Resistência à Doença/genética , Hordeum/genética , Doenças das Plantas/genéticaRESUMO
PURPOSE: Multiple efforts are underway to increase the inclusion of racial minority participants in genomic research and new forms of individualized medicine. These efforts should include studies that characterize how individuals from minority communities experience genomic medicine in diverse health-care settings and how they integrate genetic knowledge into their understandings of health-care needs. METHODS: As part of a large, multisite genomic sequencing study, we surveyed individuals to assess their decision to pursue genomic risk evaluation. Participants included Latino patients recruited at Mountain Park Health Center, a Federally Qualified Health Center in Phoenix, Arizona, and non-Latino patients recruited at a large academic medical center (Mayo Clinic in Rochester, MN). Both groups agreed to receive individualized genomic risk assessments. RESULTS: Comparisons between cohorts showed that Latino respondents had lower levels of decisional conflict about pursuing genomic screening but generally scored lower on genetic knowledge. Latino respondents were also more likely to have concerns about the misuse of genomic information, despite both groups having similar views about the value of genomic risk evaluation. CONCLUSION: Our results highlight the importance of evaluating sociocultural factors that influence minority patient engagement with genomic medicine in diverse health-care settings.
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Hispânico ou Latino , Medicina de Precisão , Estudos de Coortes , Genômica , Hispânico ou Latino/genética , Humanos , Grupos MinoritáriosRESUMO
Herein, we disclose an efficient Pd(II)-catalyzed site selective C8 alkenylation of imidazo[1,2-a]pyridines with electronically biased olefinic substrates. Notably, besides the presence of four C-H sites available, selective mono-alkenylation was achieved by N-chelation overriding O-chelation. The versatility and scalability of the catalysis enabled the selective late-stage functionalization of a marketed drug, zolimidine. Various substituted heteroaryl alkenes can be afforded with moderate to good yields with high C8 regioselectivity.
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OBJECTIVES: To 1) analyze the short-term biochemical improvements and clinical outcomes following treatment of children with post-severe acute respiratory syndrome coronavirus-2 inflammatory syndrome (multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2) admitted to U.K. PICUs and 2) collate current treatment guidance from U.K. PICUs. DESIGN: Multicenter observational study. SETTING: Twenty-one U.K. PICUs. PATIENTS: Children (< 18 yr) admitted to U.K. PICUs between April 1, 2020, and May 10, 2020, fulfilling the U.K. case definition of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Routinely collected, deidentified data were analyzed. Propensity score and linear mixed effects models were used to analyze the effect of steroids, IV immunoglobulin, and biologic agents on changes in C-reactive protein, platelet counts, and lymphocyte counts over the course of PICU stay. Treatment recommendations from U.K. clinical guidelines were analyzed. Over the 6-week study period, 59 of 78 children (76%) received IV immunoglobulin, 57 of 78 (73%) steroids, and 18 of 78 (24%) a biologic agent. We found no evidence of a difference in response in clinical markers of inflammation between patients with multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 who were treated with IV immunoglobulin, steroids, or biologics, compared with those who were not. By the end of the study period, most patients had received immunomodulation. The 12 patients who did not receive any immunomodulators had similar decrease in inflammatory markers as those treated. Of the 14 guidelines analyzed, the use of IV immunoglobulin, steroids, and biologics was universally recommended. CONCLUSIONS: We were unable to identify any short-term benefit from any of the treatments, or treatment combinations, administered. Despite a lack of evidence, treatment guidelines for multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 have become very similar in advising step-wise treatments. Retaining clinical equipoise regarding treatment will allow clinicians to enroll children in robust clinical trials to determine the optimal treatment for this novel important condition.
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COVID-19 , Criança , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
OBJECTIVE: This article describes the methodology used for the Pediatric Craniofacial Collaborative Group (PCCG) Consensus Conference. DESIGN: This is a novel Consensus Conference of national experts in Pediatric Craniofacial Surgery and Anesthesia, who will follow standards set by the Institute of Medicine and using the Research and Development/University of California, Los Angeles appropriateness method, modeled after the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. Topics related to pediatric craniofacial anesthesia for open cranial vault surgery were divided into twelve subgroups with a systematic review of the literature. SETTING: A group of 20 content experts met virtually between 2019 and 2020 and will collaborate in their selected topics related to perioperative management for pediatric open cranial vault surgery for craniosynostosis. These groups will also identify where future research is needed. CONCLUSIONS: Experts in pediatric craniofacial surgery and anesthesiology are developing recommendations on behalf of the Pediatric Craniofacial Collaborative Group for perioperative management of patients undergoing open cranial vault surgery for craniosynostosis and identifying future research priorities.