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1.
Artículo en Inglés | MEDLINE | ID: mdl-39166799

RESUMEN

OBJECTIVE: Breast milk (BM) enhancement is often used to meet the nutritional needs of preterm infants after hospital discharge to achieve optimal growth. This study compared growth at 18-28 months corrected age (CA) among very preterm (VP) and very low birth weight (VLBW) infants discharged from the neonatal intensive care units (NICUs) on two BM enhancements. METHODS: We conducted a retrospective chart review study of infants born between January 1, 2013 and December 31, 2017, with gestational age < 32 weeks or birthweight < 1500 g, discharged from the NICU on BM enhancements; fortification of BM with infant formula additives (BM-F) or unfortified BM supplemented with bottle feeds of infant formula (BM-S). BM enhancements were nonrandomized and determined by the medical team. A linear mixed model regression analysis with propensity score matching was used to estimate the adjusted associations between the nutrition plan at discharge and growth outcomes at 18-28 months CA follow-up. RESULTS: Two hundred and fifty-one VLBW/VP infants were included. Compared with BM-S, infants discharged on BM-F were more likely to continue receiving BM at 8-12 months CA, and had lower head circumference, weight-for-length z scores, and higher incidence of moderate malnutrition (p ≤ 0.01). After adjusting for confounders, discharge on BM-F was associated with a lower incidence of overweight/obesity at 18-28 months CA (odds interval: 0.45; confidence interval: 0.21-0.96; p = 0.04). CONCLUSIONS: This retrospective study suggests that VLBW/VP infants discharged on BM-F received BM longer, had lower growth parameter and were less likely to be overweight/obese at 18-28 months CA. Further studies are needed to evaluate the role of postdischarge nutrition on preterm born children's growth, metabolic disease, and neurodevelopmental outcomes.

2.
Microb Genom ; 10(8)2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39133528

RESUMEN

At the end of 2022 into early 2023, the UK Health Security Agency reported unusually high levels of scarlet fever and invasive disease caused by Streptococcus pyogenes (StrepA or group A Streptococcus). During this time, we collected and genome-sequenced 341 non-invasive throat and skin S. pyogenes isolates identified during routine clinical diagnostic testing in Sheffield, a large UK city. We compared the data with that obtained from a similar collection of 165 isolates from 2016 to 2017. Numbers of throat-associated isolates collected peaked in early December 2022, reflecting the national scarlet fever upsurge, while skin infections peaked later in December. The most common emm-types in 2022-2023 were emm1 (28.7 %), emm12 (24.9 %) and emm22 (7.7 %) in throat and emm1 (22 %), emm12 (10 %), emm76 (18 %) and emm49 (7 %) in skin. While all emm1 isolates were the M1UK lineage, the comparison with 2016-2017 revealed diverse lineages in other emm-types, including emm12, and emergent lineages within other types including a new acapsular emm75 lineage, demonstrating that the upsurge was not completely driven by a single genotype. The analysis of the capsule locus predicted that only 51 % of throat isolates would produce capsule compared with 78% of skin isolates. Ninety per cent of throat isolates were also predicted to have high NADase and streptolysin O (SLO) expression, based on the promoter sequence, compared with only 56% of skin isolates. Our study has highlighted the value in analysis of non-invasive isolates to characterize tissue tropisms, as well as changing strain diversity and emerging genomic features which may have implications for spillover into invasive disease and future S. pyogenes upsurges.


Asunto(s)
Infecciones Estreptocócicas , Streptococcus pyogenes , Streptococcus pyogenes/genética , Streptococcus pyogenes/clasificación , Streptococcus pyogenes/aislamiento & purificación , Humanos , Reino Unido , Infecciones Estreptocócicas/microbiología , Proteínas de la Membrana Bacteriana Externa/genética , Antígenos Bacterianos/genética , Faringe/microbiología , Escarlatina/microbiología , Escarlatina/epidemiología , Proteínas Portadoras/genética , Estreptolisinas/genética , Secuenciación Completa del Genoma/métodos , Proteínas Bacterianas/genética , Filogenia , Niño , Adulto , NAD+ Nucleosidasa/genética , NAD+ Nucleosidasa/metabolismo , Piel/microbiología , Preescolar , Masculino
3.
Artículo en Inglés | MEDLINE | ID: mdl-39036578

RESUMEN

This study, conducted in Pakistan, examines the perspectives of 1200 physicians across diverse specialties regarding Left Atrial Appendage Occlusion (LAAO) procedures for atrial fibrillation (AF) patients with chronic kidney disease (CKD). Using a random sampling approach, physicians participated in a survey that assessed their familiarity with LAAO, views on its effectiveness and safety, experience levels, and encountered challenges. The results unveil a spectrum of knowledge levels among physicians, reinforcing the need for tailored medical education and training programs. The majority of respondents were between 30 and 49 years old (59.8 %). A notable proportion, 33.3 %, had limited or no knowledge of LAAO, with 16.7 % having never heard of the procedure, and 16.7 % having limited knowledge but no experience. About 36.2 % of physicians believed LAAO was moderately to extremely effective in reducing stroke risk, with 23.3 % considering it very effective and 25.4 % believing it to be extremely effective. The most commonly cited clinical indications were a history of recurrent strokes despite anticoagulation (34.6 %) and a high CHA2DS2-VASc score (27.3 %). Renal considerations played a significant role, with 33.1 % considering LAAO for CKD stage 4 or 5 patients with elevated stroke risk. Patient preferences, such as a desire to avoid long-term anticoagulant use, were important for 28.7 % of physicians. Identified challenges encompass limited equipment access, training gaps, patient reluctance, and administrative complexities. Furthermore, the study underscores the pivotal role of shared decision-making in healthcare delivery. These findings lay essential groundwork for improving LAAO utilization and patient-centered care in Pakistan's healthcare system.

4.
PLoS One ; 19(5): e0303426, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38805437

RESUMEN

This paper aims to extend the applications of the projected fractional improved Adomian Decomposition method (fIADM) to the fractional order new coupled Korteweg-de Vries (cKdV) system. This technique is significantly recognized for its effectiveness in addressing nonlinearities and iteratively handling fractional derivatives. The approximate solutions of the fractional-order new cKdV system are obtained by employing the improved ADM in fractional form. These solutions play a crucial role in designing and optimizing systems in engineering applications where accurate modeling of wave phenomena is essential, including fluid dynamics, plasma physics, nonlinear optics, and other mathematical physics domains. The fractional order new cKdV system, integrating fractional calculus, enhances accuracy in modeling wave interactions compared to the classical cKdV system. Comparison with exact solutions demonstrates the high accuracy and ease of application of the projected method. This proposed technique proves influential in resolving fractional coupled systems encountered in various fields, including engineering and physics. Numerical results obtained using Mathematica software further verify and demonstrate its efficacy.


Asunto(s)
Algoritmos , Modelos Teóricos , Dinámicas no Lineales , Programas Informáticos , Simulación por Computador
5.
Front Pediatr ; 12: 1377195, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38655274

RESUMEN

Despite the global improvements in neonatal outcomes, mortality and morbidity rates among preterm infants are still unacceptably high. Therefore, it is crucial to thoroughly analyze the factors that affect these outcomes, including sex, race, and social determinants of health. By comprehending the influence of these factors, we can work towards reducing their impact and enhancing the quality of neonatal care. This review will summarize the available evidence on sex differences, racial differences, and social determinants of health related to neonates. This review will discuss sex differences in neonatal outcomes in part I and racial differences with social determinants of health in part II. Research has shown that sex differences begin to manifest in the early part of the pregnancy. Hence, we will explore this topic under two main categories: (1) Antenatal and (2) Postnatal sex differences. We will also discuss long-term outcome differences wherever the evidence is available. Multiple factors determine health outcomes during pregnancy and the newborn period. Apart from the genetic, biological, and sex-based differences that influence fetal and neonatal outcomes, racial and social factors influence the health and well-being of developing humans. Race categorizes humans based on shared physical or social qualities into groups generally considered distinct within a given society. Social determinants of health (SDOH) are the non-medical factors that influence health outcomes. These factors can include a person's living conditions, access to healthy food, education, employment status, income level, and social support. Understanding these factors is essential in developing strategies to improve overall health outcomes in communities.

6.
Children (Basel) ; 11(3)2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38539300

RESUMEN

Challenging the assumption of uniform nutritional needs in preterm feeding, this study identifies crucial sex-specific disparities in formula milk intake and growth among late preterm infants. Premature infants have difficulty regulating their oral intake during feeds, which is why clinicians prescribe feeding volume, calories, and protein via the nasogastric route. However, premature male and female infants have different body compositions at birth, and, subsequently, there is no evidence to suggest that male and female preterm infants differ in their nutritional consumption once they begin feeding ad libitum. This study investigates whether there are any differences in the volume and nutrient intake between the sexes when fed formula ad libitum. METHODS: The study involved a retrospective analysis of preterm infants admitted to the NICU and evaluated between 34 0/7 and 36 6/7 weeks of corrected gestation. Late preterm infants appropriate for gestational age who were spontaneously fed formula milk ad-lib and free of any respiratory support for at least two days were included. The study excluded infants with short gut syndrome, severe chromosomal anomalies, or congenital heart conditions. We included 85 male and 85 female infants in this study. The data collected included sex, gestational age, birth weight, anthropometric data at birth, maternal data, nutritional intake, and neonatal morbidity. RESULTS: This study found that female infants consumed more volume, protein, and calories than male infants. The mean formula intake in female and male infants was 145.5 ± 20.8 mL/kg/d and 135.3 ± 19.3 mL/kg/d, respectively, with p = 0.002. However, ad-lib feeding duration was not different between the sexes. Growth velocity was also higher in female infants. CONCLUSIONS: This study is the first to demonstrate differences in formula milk intake among late preterm infants fed ad libitum. Additional research is needed to confirm our findings and understand sex-specific differences in neonatal nutrition in extremely early preterm infants.

7.
Antimicrob Agents Chemother ; 68(4): e0153323, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38477706

RESUMEN

Pharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic approach using dried blood spots (DBS) to evaluate a population pharmacokinetic model of metronidazole in critically ill preterm infants of gestational age (GA) ≤31 weeks from the Metronidazole Pharmacokinetics in Premature Infants (PTN_METRO, NCT01222585) study. First, we used linear correlation to compare 42 paired DBS and plasma metronidazole concentrations from 21 preterm infants [mean (SD): post natal age 28.0 (21.7) days, GA 26.3 (2.4) weeks]. Using the resulting predictive equation, we estimated plasma metronidazole concentrations (ePlasma) from 399 DBS collected from 122 preterm and term infants [mean (SD): post natal age 16.7 (15.8) days, GA 31.4 (5.1) weeks] from the Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP, NCT01994993) trial. When evaluating the PTN_METRO model using ePlasma from the SCAMP trial, we found that the model generally predicted ePlasma well in preterm infants with GA ≤31 weeks. When including ePlasma from term and preterm infants with GA >31 weeks, the model was optimized using a sigmoidal Emax maturation function of postmenstrual age on clearance and estimated the exponent of weight on volume of distribution. The optimized model supports existing dosing guidelines and adds new data to support a 6-hour dosing interval for infants with postmenstrual age >40 weeks. Using an opportunistic DBS to externally validate and optimize a metronidazole population pharmacokinetic model was feasible and useful in this vulnerable population.


Asunto(s)
Recien Nacido Prematuro , Metronidazol , Humanos , Lactante , Recién Nacido , Antibacterianos/farmacocinética , Enfermedad Crítica , Edad Gestacional , Metronidazol/farmacocinética
8.
Biotechnol Bioeng ; 120(8): 2092-2116, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37475649

RESUMEN

Amylases are biologically active enzymes that can hydrolyze starch to produce dextrin, glucose, maltose, and oligosaccharides. The amylases contribute approximately 30% to the global industrial enzyme market. The globally produced amylases are widely used in textile, biofuel, starch processing, food, bioremediation of environmental pollutants, pulp, and paper, clinical, and fermentation industries. The purpose of this review article is to summarize recent trends and aspects of α-amylases, classification, microbial production sources, biosynthesis and production methods, and its broad-spectrum applications for industrial purposes, which will depict the latest trends in α-amylases production. In the present article, we have comprehensively compared the biodiversity of α-amylases in different model organisms ranging from archaea to eukaryotes using in silico structural analysis tools. The detailed comparative analysis: regarding their structure, function, cofactor, signal peptide, and catalytic domain along with their catalytic residues of α-amylases in 16 model organisms were discussed in this paper. The comparative studies on alpha (α) amylases' secondary and tertiary structures, multiple sequence alignment, transmembrane helices, physiochemical properties, and their phylogenetic analysis in model organisms were briefly studied. This review has documented the recent trends and future perspectives of industrially important novel thermophilic α-amylases. In conclusion, this review sheds light on the current understanding and prospects of α-amylase research, highlighting its importance as a versatile enzyme with numerous applications and emphasizing the need for further exploration and innovation in this field.


Asunto(s)
Amilasas , alfa-Amilasas , alfa-Amilasas/química , alfa-Amilasas/genética , Filogenia , Amilasas/genética , Catálisis , Almidón
9.
Adv Sci (Weinh) ; 10(26): e2301872, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37395639

RESUMEN

The increasing demand for clean energy conversion and storage has increased interest in hydrogen production via electrolytic water splitting. However, the simultaneous production of hydrogen and oxygen in this process poses a challenge in extracting pure hydrogen without using ionic conducting membranes. Researchers have developed various innovative designs to overcome this issue, but continuous water splitting in separated tanks remains a desirable approach. This study presents a novel, continuous roll-to-roll process that enables fully decoupled hydrogen evaluation reaction (HER) and oxygen evolution reaction (OER) in two separate electrolyte tanks. The system utilizes specially designed "cable-car" electrodes (CCE) that cycle between the HER and OER tanks, resulting in continuous hydrogen production with a purity of over 99.9% and Coulombic efficiency of 98% for prolonged periods. This membrane-free water splitting system offers promising prospects for scaled-up industrial-scale green hydrogen production, as it reduces the cost and complexity of the system, and allows for the use of renewable energy sources to power the electrolysis process, thus reducing the carbon footprint of hydrogen production.

10.
Small ; 19(36): e2207759, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37150859

RESUMEN

Homogeneous and nanometric metal clusters with unique electronic structures are promising for catalysis, however, common synthesis techniques for metal clusters suffer from large size and even metal nanocrystals attributing to their high surface energy and unsaturated configurations. Herein, a generalized rapid annealing strategy for synthesizing a series of supported metal clusters as superior catalysts is developed. Remarkably, TiO2 supported platinum nanoclusters (Pt NC/TiO2 ) exhibits the excellent catalytic activity to realize phenol hydrogenation under mild conditions. The complete phenol conversion rate and 100% selectivity toward KA oil are achieved in aqueous solution at room temperature and normal pressure. Semi-continuous scale up production of KA oil is successfully performed under mild conditions. Such excellent performance mainly originates from the partial reconstruction of Pt NC/TiO2 in aqueous phenol solution. Considering that the phenol can be produced from lignin, this study underpins a facile, sustainable, and economical route to synthesize nylon from biomass.

11.
Am J Perinatol ; 2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-36963432

RESUMEN

OBJECTIVE: This study aimed to estimate national time trends of overall and statewise antibiotic utilization (AU) rates for suspected neonatal sepsis (SNS) in the United States. STUDY DESIGN: In this cross-sectional study, we used retrospective linked birth cohort and vital records data from the Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research database for the years 2016 to 2020 and analyzed data containing antibiotic use for SNS. The primary outcome was proportional national and state-specific AU rates per 1,000 live births during the birth hospitalization. Secondary outcomes included overall trends and association between maternal education, race, sex, chorioamnionitis, mode of delivery, gestational age at birth, Apgar's scores, and insurance status with antibiotics exposure for SNS among newborns. Contingency tables, two-tailed t-test, and chi-square for independence tests were performed with statistical significance set at p < 0.05. RESULTS: For a birth cohort of >18 million, 2.2% of infants received antibiotics during birth hospitalization nationwide. There were wide variations in AU among U.S. states and territories, whereas overall treatment rates decreased by 16.1% (95% confidence interval [CI]: 15.2-17.0; p < 0.001). Compared with White newborns, Black newborns had higher AU rates (odds ratio [OR]: 1.33; 95% CI: 1.32-1.34), and Asians had the lowest rates (OR: 0.96; 95% CI: 0.95-0.97). There was a significant difference in mean AU rates by race (p < 0.001). Chorioamnionitis at birth significantly increased the odds for AU (OR: 14.5 ;95% CI: 14.4-14.6), although AU rates for chorioamnionitis showed a significant downward trend (OR: 0.52; 95% CI: 0.50-0.53) during the study period. CONCLUSION: Our findings suggest that there has been a gradual decline in AU for SNS in more than a third of states in last 5 years. While risk-based management approaches achieve widespread implementation, state- and nationwide quality improvement collaborates might have contributed to the relative decline in antibiotic use in newborns. Further studies are warranted to understand factors related to practice variation in the management of SNS in the United States KEY POINTS: · Early and prolonged use of antibiotics can lead to altered gut microbiome and adverse long-term neonatal outcomes.. · There is considerable clinical practice variation in antibiotic-prescribing practices for suspected neonatal sepsis.. · This cross-sectional study reports the differences in neonatal antibiotic usage patterns by region and maternal factors.. · Antibiotic use should be limited to newborns at high risk of infection and proven sepsis.. · Judicious use of antibiotics can be promoted by following evidence-based approaches to sepsis risk assessment..

12.
JAMA Pediatr ; 177(1): 90-93, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36315137

RESUMEN

This cross-sectional study reports recent trends in US national live births at 22 completed weeks' gestational age and analyzes the association of antenatal corticosteroid use and cesarean delivery with birth-linked survival at birth certificate reporting time, 27 days of life, and 364 days of life.


Asunto(s)
Corticoesteroides , Nacimiento Prematuro , Humanos , Embarazo , Femenino , Estados Unidos , Corticoesteroides/uso terapéutico , Edad Gestacional
14.
Small ; 18(52): e2204302, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36251779

RESUMEN

Photoluminescence (PL) in state-of-the-art 2D materials suffers from narrow spectral coverage, relatively broad linewidths, and poor room-temperature (RT) functionality. The authors report ultra-narrow linewidth photo-emitters (ULPs) across the visible to near-infrared wavelength at RT in polymorphic selenium nanoflakes (SeNFs), synthesized via a hot-pressing strategy. Photo-emitters in NIR exhibit full width at half maximum (Γ) of 330 ± 90 µeV, an order of magnitude narrower than the reported ULPs in 2D materials at 300 K, and decrease to 82 ± 70 µeV at 100 K, with coherence time (τc ) of 21.3 ps. The capping substrate enforced spatial confinement during thermal expansion at 250 °C is believed to trigger a localized crystal symmetry breaking in SeNFs, causing a polymorphic transition from the semiconducting trigonal (t) to quasi-metallic orthorhombic (orth) phase. Fine structure splitting in orth-Se causes degeneracy in defect-associated bright excitons, resulting in ultra-sharp emission. Combined theoretical and experimental findings, an optimal biaxial compressive strain of -0.45% cm-1 in t-Se is uncovered, induced by the coefficient of thermal expansion mismatch at the selenium/sapphire interface, resulting in bandgap widening from 1.74 to 2.23 ± 0.1 eV. This report underpins the underlying correlation between crystal symmetry breaking induced polymorphism and RT ULPs in SeNFs, and their phase change characteristics.

15.
Nanoscale Adv ; 4(6): 1608-1616, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36134375

RESUMEN

Optical filters operating in the visible region of the spectrum are highly desired for applications ranging from optical communication and sensing to fluorescence microscopy and skin therapy. However, complex fabrication procedures and/or inferior performance, limit the practical applications of previously reported thin-film-based optical filters. Herein, we describe the structual design concepts and facile fabrication of vertically stacked heterolayers of TiO2/Al2O3 to obtain a bandpass filter and a longwave pass edge filter operating in the spectral range 410-600 nm and 400-597 nm, respectively. The optical filters are designed according to MacLeod simulation and fabricated via magnetron sputtering, depositing alternative stacks of low (Al2O3) and high (TiO2) refractive index materials with different thicknesses, as confirmed by spectroscopic ellipsometry. Owing to a reasonable matching between the design and the fabrication, our developed TiO2/Al2O3 heterolayer optical filters exhibited 54.60% transmission for 7-layer longwave pass edge filter and 15% reflectance for 14-layer bandpass filter of a selective set of wavelengths (400-800 nm).

16.
Tuberculosis (Edinb) ; 136: 102253, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36067572

RESUMEN

Tuberculosis (TB) stays a major cause of death globally after COVID-19 and HIV. An early diagnosis to control TB effectively, needs a fast reliable diagnostic method with high sensitivity. Serodiagnosis involving polyclonal antibodies detection against an antigen of Mycobacterium tuberculosis (Mtb) in serum samples can be instrumental. In our study, Rv3874 and Rv3875 antigens were cloned, expressed, and purified individually and as a chimeric construct in Escherichia coli BL21. Enzyme-Linked Immunosorbent Assay (ELISA) based findings revealed that the Rv3874-Rv3875 chimeric construct was two-fold more sensitive (59.7%) than the individual sensitivities of Rv3874 (28.4%) and Rv3875 (24.9%) for 201 serum TB positive samples. Furthermore, the fusion construct was a little more sensitive (60.4%) for male subjects than that for females (58.8%). Lastly, our preliminary findings, molecular insights of secondary structure, and statistical and in silico analysis of each construct also advocate that CEP can be considered a better immunodiagnostic tool in addition to previously reported EC skin test.


Asunto(s)
COVID-19 , Mycobacterium tuberculosis , Tuberculosis , Antígenos Bacterianos , Ensayo de Inmunoadsorción Enzimática/métodos , Escherichia coli , Femenino , Humanos , Masculino , Mycobacterium tuberculosis/genética , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Sensibilidad y Especificidad , Pruebas Serológicas , Tuberculosis/diagnóstico
17.
Nano Lett ; 22(17): 7212-7219, 2022 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-36054509

RESUMEN

The ongoing coronavirus (COVID-19) pandemic requires enormous production of facemasks and related personal protection materials, thereby increasing the amount of nondegradable plastic waste. The core material for facemasks is melt-blown polypropylene (PP) fiber. Each disposable facemask consumes ∼0.7 g of PP fibers, resulting in annual global consumption and disposal of more than 1 150 000 tons of PP fibers annually. Herein, we developed a laser-assisted melt-blown (LAMB) technique to manufacture PP nanofibers with a quality factor of 0.17 Pa-1 and significantly reduced the filter's weight. We demonstrated that a standard surgical facemask could be made with only 0.13 g of PP nanofibers, saving approximately 80% of the PP materials used in commercial facemasks. Theoretical analysis and modeling were also conducted to understand the LAMB process. Importantly, nanofibers can be easily scaled up for mass production by upgrading traditional melt blown line with scanning laser-assisted melt-blown (SLAMB).


Asunto(s)
COVID-19 , Nanofibras , COVID-19/prevención & control , Humanos , Rayos Láser , Máscaras , Polipropilenos
18.
Proc Natl Acad Sci U S A ; 119(31): e2205412119, 2022 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-35858383

RESUMEN

Camelid single-domain antibodies, also known as nanobodies, can be readily isolated from naïve libraries for specific targets but often bind too weakly to their targets to be immediately useful. Laboratory-based genetic engineering methods to enhance their affinity, termed maturation, can deliver useful reagents for different areas of biology and potentially medicine. Using the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and a naïve library, we generated closely related nanobodies with micromolar to nanomolar binding affinities. By analyzing the structure-activity relationship using X-ray crystallography, cryoelectron microscopy, and biophysical methods, we observed that higher conformational entropy losses in the formation of the spike protein-nanobody complex are associated with tighter binding. To investigate this, we generated structural ensembles of the different complexes from electron microscopy maps and correlated the conformational fluctuations with binding affinity. This insight guided the engineering of a nanobody with improved affinity for the spike protein.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Afinidad de Anticuerpos , SARS-CoV-2 , Anticuerpos de Dominio Único , Glicoproteína de la Espiga del Coronavirus , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/genética , Anticuerpos Antivirales/química , Anticuerpos Antivirales/genética , Afinidad de Anticuerpos/genética , Microscopía por Crioelectrón , Entropía , Ingeniería Genética , Humanos , Unión Proteica , Dominios Proteicos , SARS-CoV-2/inmunología , Anticuerpos de Dominio Único/química , Anticuerpos de Dominio Único/genética , Glicoproteína de la Espiga del Coronavirus/inmunología
19.
Placenta ; 124: 62-66, 2022 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-35640456

RESUMEN

INTRODUCTION: COVID-19 has been associated with several adverse pregnancy outcomes, including perinatal loss. Differential effects of COVID-19 in a twin pregnancy may provide unique insights into virus-placental interactions. We present a case of perinatal loss of a female fetus with survival of the male co-twin in a pregnancy complicated by COVID-19 and premature delivery. METHODS: Viral detection methods recommended by the NICHD task force were used to identify SARS-CoV-2 and its viral receptors in the placentas and fetal tissue (Antoun et al., 2020) [1] RESULTS: Compared with the surviving twin, we found a more severe intervillous necrosis and a relatively low detection of ACE2 membranous expression in the syncytiotrophoblasts of the female twin that succumbed. DISCUSSION: The interactions of SARS-CoV-2 and ACE2 at the maternal fetal interface within the placenta may play a significant role in perinatal loss, and the effects of fetal sex and gestational age at time of infection need to be explored further.


Asunto(s)
COVID-19 , Complicaciones Infecciosas del Embarazo , Enzima Convertidora de Angiotensina 2 , Femenino , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Placenta/metabolismo , Embarazo , Complicaciones Infecciosas del Embarazo/patología , SARS-CoV-2
20.
Pediatr Res ; 92(6): 1695-1704, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35338349

RESUMEN

BACKGROUND: The aim of this study was to investigate the influence of early-life pain/stress and medical characteristics on neurobehavioral outcomes in preterm infants. METHODS: A prospective cohort study was conducted with 92 preterm infants (28-32 weeks gestational age [GA]). Early-life pain/stress was measured via the Neonatal Infant Stressor Scale (NISS) during the first 28 days of NICU hospitalization. Neurobehavioral outcomes were evaluated using the NICU Network Neurobehavioral Scale at 36-38 weeks post-menstrual age. Functional regression and machine learning models were performed to investigate the predictors of neurobehavioral outcomes. RESULTS: Infants experienced daily acute pain/stress (24.99 ± 7.13 frequencies) and chronic events (41.13 ± 17.81 h). Up to 12 days after birth, both higher acute and chronic NISS scores were associated with higher stress scores; and higher chronic NISS scores were also related to lower self-regulation and quality of movement. Younger GA predicted worse neurobehavioral outcomes; GA < 31.57 weeks predicted worse stress/abstinence, self-regulation, and excitability; GA < 30.57 weeks predicted poor quality of movement. A higher proportion of maternal breastmilk intake predicted better self-regulation, excitability, and quality of movement in older GA infants. CONCLUSIONS: Preterm infants are vulnerable to the impact of early-life pain/stress. Neurobehavioral outcomes are positively associated with increased GA and higher maternal breastmilk intake. IMPACT: During the first 12 days of life, preterm infant neurobehavioral outcomes were vulnerable to the negative impact of acute and chronic pain/stress. Future research is warranted to investigate the long-term effects of early-life pain/stress on neurobehavioral outcomes. Gestational age remains one of the critical factors to predict neurobehavioral outcomes in preterm infants; older gestational age significantly predicted better neurobehavioral outcomes. Feeding with a higher proportion of maternal breastmilk predicted better neurobehavioral outcomes. Future research is warranted to investigate how maternal breastmilk may buffer the negative effects of early-life pain/stress on neurobehavioral outcomes.


Asunto(s)
Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Lactante , Humanos , Recién Nacido , Anciano , Recien Nacido Prematuro/fisiología , Estudios Prospectivos , Hospitalización , Dolor
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