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1.
J Nutr ; 154(1): 152-162, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37717629

RESUMEN

BACKGROUND: The taxonomic composition of the gut microbiome undergoes rapid development during the first 2-3 y of life. Poor diet during complementary feeding has been associated with alterations in infant growth and compromised bone, immune system, and neurodevelopment, but how it may affect gut microbial composition is unknown. OBJECTIVES: This cross-sectional study aimed to examine the associations between early-life nutrition and the developing infant gut microbiota at 6 mo of age. METHODS: Latino mother-infant pairs from the Mother's Milk Study (n = 105) were included. Infant gut microbiota and dietary intake were analyzed at 6 mo of age using 16S ribosomal RNA amplicon sequencing and 24-h dietary recalls, respectively. Poisson generalized linear regression analysis was performed to examine associations between dietary nutrients and microbial community abundance while adjusting for infants' mode of delivery, antibiotics, infant feeding type, time of introduction of solid foods, energy intake, and body weight. A P value of <0.05 was used to determine the statistical significance in the study. RESULTS: Infants with higher consumption of total sugar exhibited a lower relative abundance of the genera Bacteroides (ß = -0.01; 95% CI: -0.02, -0.00; P = 0.03) and genus Clostridium belonging to the Lachnospiraceae family (ß = -0.02; 95% CI: -0.03, -0.00; P = 0.01). In addition, a higher intake of free sugar (which excludes sugar from milk, dairy, and whole fruit) was associated with several bacteria at the genus level, including Parabacteroides genus (ß = 0.03; 95% CI: 0.01, 0.05; P = 0.001). Total insoluble fiber intake was associated with favorable bacteria at the genus level such as Faecalibacterium (ß = 0.28; 95% CI: 0.03, 0.52; P = 0.02) and Coprococcus (ß = 0.28; 95% CI: 0.02, 0.52; P = 0.03). CONCLUSION: These findings demonstrate that early-life dietary intake at 6 mo impacts the developing gut microbiome associated with the presence of both unfavorable gut microbes and dietary fiber-associated commensal microbes.


Asunto(s)
Microbioma Gastrointestinal , Lactante , Humanos , Microbioma Gastrointestinal/genética , Azúcares de la Dieta , Estudios Transversales , Bacterias/genética , Fibras de la Dieta , Leche Humana , ARN Ribosómico 16S/genética , Heces/microbiología
2.
Artículo en Inglés | MEDLINE | ID: mdl-38728602

RESUMEN

Rapid control of the content of Parkinson's drugs in biological fluids and pharmaceutical formulations is of great importance because changes in the concentration of these drugs affect their bioavailability and biopharmaceutical properties. Therefore, we presented a simple and convenient method for the ratiometric detection of carbidopa and levodopa for carbon dots (CDs) dual-fluorescent emission. Dual-emission CDs were prepared from chitosan using a microwave method, following which the surface was chemically modified with terephthalaldehyde. CDs had two strong well-separated peaks at 445 and 510 nm. The relative measurement of carbidopa and levodopa was based on the static extinction of CDs at 445 nm and increase at 510 nm, respectively. The linear range for carbidopa measurement was 2.5-300 nM, with a limit of detection (LOD) of 2.1 nM, and a relative standard deviation (RSD) of 1.68%. Further, the linear range for levodopa measurement was equal to 3.0-400 nM, with LOD and RSD% of 2.8 nM and 3.5%, respectively. Also, selectivity of ratiometric sensor in the presence of interferences was investigated, which showed that the recovery of carbidopa and levodopa in serum and urine samples has changed between 96.80% and 116.24% with RSD% 0.11-0.77. CDs also provided good results for the determination of carbidopa and levodopa in real samples, and had high selectivity in the presence of possible interferences.

3.
Pediatr Dermatol ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38684232

RESUMEN

Actinic prurigo is a rare photodermatosis characterized by pruritic papulonodular lesions. Treatment is challenging, especially in children, as sun protection strategies need to be rigorously implemented and symptoms often persist throughout the year. Herein, we present a case of actinic prurigo in an 8-year-old patient with rapid and successful relief with baricitinib.

4.
Expert Opin Emerg Drugs ; 27(3): 241-261, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35929974

RESUMEN

INTRODUCTION: Acne vulgaris is one of the commonest dermatoses encountered in a dermatology clinic. Although the inflammatory processes are centered around the pilosebaceous unit, a myriad of external factors that alter the pathogenesis have been hypothesized. Newer therapies are focused on targeting these as possible scaffolds for drug development. Existing topical and oral medications have considerable overlap between pharmacotherapy and cosmeceuticals directed toward acne treatment making new drug development extremely competitive and financially burdening. Teratogenicity associated with retinoids, cutaneous adverse effects of topical anti-acne medications, and lack of long-term remission induction are a few hindrances that have to be tackled by novel therapies. AREAS COVERED: Numerous topical and systemic medications for acne vulgaris are undergoing clinical trials presently. The review has dealt with anti-acne drugs undergoing phase II and III clinical trials with emphasis on the rationale of various combinations in tandem with the complex pathogenesis of the disease. EXPERT OPINION: The current strategies in new drug development target sebocyte function, neo-inflammatory mediators, and methods combatting drug resistance while broadening the anti-microbial spectrum against Cutibacterium acnes. A holistic approach is pivotal to strengthen the management protocol for acne to achieve precision dermatological practice.


Asunto(s)
Acné Vulgar , Antibacterianos , Humanos , Antibacterianos/efectos adversos , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/etiología , Acné Vulgar/patología , Retinoides/efectos adversos , Administración Cutánea , Quimioterapia Combinada , Ensayos Clínicos Fase II como Asunto
5.
Med J Islam Repub Iran ; 36: 138, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36479533

RESUMEN

Background: Blood sampling is expensive, time-consuming, invasive, and requires technical facilities, which can be replaced by more convenient samples such as saliva. C-reactive protein (CRP) is a widely used biomarker in the management of many disorders and plasma CRP (pCRP) is suggested to be replaced by salivary CRP (sCRP). This study aimed to systematically review all available literature on the sCRP levels in systemic and oral disorders and how sCRP and pCRP levels correlate among these patients and healthy individuals. Methods: In this systematic review, a PubMed, Embase, Scopus, and Google Scholar search was conducted on October-2021 to identify all research investigating sCRP levels in systemic and oral disorders. Results: A total of 130 publications were analyzed in the review. Most of the studies reported that sCRP and pCRP levels are correlated, and sCRP is a reliable alternative for pCRP level for the diagnosis and management of medical conditions. sCRP has been measured in many different medical and oral disorders and significantly correlated with disease activity in most cases. Conclusion: Salivary CRP is a good alternative for Plasma CRP levels in most cases.

6.
Metab Eng ; 64: 52-63, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33465478

RESUMEN

Synthetic biology enables the production of small molecules by recombinant microbes for pharma, food, and materials applications. The secretion of products reduces the cost of separation and purification, but it is challenging to engineer due to the limited understanding of the transporter proteins' functions. Here we describe a method for genome-wide transporter disruption that, in combination with a metabolite biosensor, enables the identification of transporters impacting the production of a given target metabolite in yeast Saccharomyces cerevisiae. We applied the method to study the transport of xenobiotic compounds, cis,cis-muconic acid (CCM), protocatechuic acid (PCA), and betaxanthins. We found 22 transporters that influenced the production of CCM or PCA. The transporter of the 12-spanner drug:H(+) antiporter (DHA1) family Tpo2p was further confirmed to import CCM and PCA in Xenopus expression assays. We also identified three transporter proteins (Qdr1p, Qdr2p, and Apl1p) involved in betaxanthins transport. In summary, the described method enables high-throughput transporter identification for small molecules in cell factories.


Asunto(s)
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Antiportadores , Ingeniería Metabólica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Ácido Sórbico , Biología Sintética
7.
FEMS Yeast Res ; 21(4)2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33893795

RESUMEN

Biotechnological production requires genetically stable recombinant strains. To ensure genomic stability, recombinant DNA is commonly integrated into the genome of the host strain. Multiple genetic tools have been developed for genomic integration into baker's yeast Saccharomyces cerevisiae. Previously, we had developed a vector toolkit EasyClone-MarkerFree for stable integration into eleven sites on chromosomes X, XI, and XII of S. cerevisiae. The markerless integration was enabled by CRISPR-Cas9 system. In this study, we have expanded the kit with eight additional intergenic integration sites located on different chromosomes. The integration efficiency into the new sites was above 80%. The expression level of green fluorescence protein (gfp) for all eight sites was similar or above XI-2 site from the original EasyClone-MarkerFree toolkit. The cellular growth was not affected by the integration into any of the new eight locations. The eight-vector expansion kit is available from AddGene.


Asunto(s)
Ingeniería Metabólica , Saccharomyces cerevisiae/genética , Sistemas CRISPR-Cas , Cromosomas Fúngicos/genética , Microbiología Industrial , Plásmidos , ARN Guía de Kinetoplastida
8.
J Headache Pain ; 22(1): 20, 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33823785

RESUMEN

BACKGROUND: Reversible Cerebral Vasoconstriction Syndrome is a condition of transient cerebral vascular spasms, which usually presents with recurrent thunderclap headaches and recovers within 3 months. Several probable triggers and underlying factors, such as sex hormones, vasoactive drugs, head trauma or surgery, and tumors, have been implicated. CASE PRESENTATION: In this paper, we present a 53-year-old woman with thunderclap headaches and normal lab tests who was radio-clinically diagnosed with reversible cerebral vasoconstriction syndrome and treated accordingly. Then, she experienced the recurrence of RCVS after about 2 years and headaches after 1 year in association with high blood pressure, high blood sugar, hypothyroidism, hyperlipidemia, and a urine metanephrine level of 5 times higher than the normal limit, suggesting a diagnosis of pheochromocytoma. After confirmation of the diagnosis with further imaging studies, surgical removal of the tumor resolved all the signs and symptoms. CONCLUSION: Often underdiagnosed, pheochromocytoma could be an important condition associated with RCVS. It is important for clinicians to bear this diagnosis in mind while dealing with similar cases of recurrent thunderclap headaches.


Asunto(s)
Cefaleas Primarias , Vasoespasmo Intracraneal , Femenino , Cefaleas Primarias/diagnóstico , Cefaleas Primarias/etiología , Humanos , Persona de Mediana Edad , Vasoconstricción , Vasoespasmo Intracraneal/diagnóstico , Vasoespasmo Intracraneal/diagnóstico por imagen
9.
Public Health Nutr ; 23(4): 691-700, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31588884

RESUMEN

OBJECTIVE: To develop and validate a Dental Nutrition Knowledge Competency Scale to assess dental health-related nutrition knowledge of low-income women. DESIGN: This is a cross-sectional study. A literature search for foods/dietary practices related to dental caries was conducted and the items were incorporated into an initial questionnaire. A panel of ten nutrition experts evaluated it for its content, readability and relevance, and a focus group of six low-income women determined its readability and comprehension. Then the questionnaire was administered to 150 low-income women. Construct validity was evaluated by item difficulty, item discrimination and factor analysis. Internal consistency reliability was tested via Cronbach's α. In a sub-sample of forty women, test-retest reliability was established. Paired-sample t tests were conducted to examine differences between test scores at the two time points, 2 weeks apart. SETTINGS: Community centres in low-income housing in Central Texas, USA. PARTICIPANTS: A total of 150 low-income women, aged 18-50 years; annual household income <250 % of the federal poverty level. RESULTS: Item difficulty and discrimination analysis resulted in elimination of eight questions. Factor analysis identified twenty-four items that loaded on three factors related to knowledge. These included foods/dietary practices that affect dental caries, added sugars in foods and on food labels, and recommended frequency of oral hygiene practices. The subscales and the completed scale exhibited good internal consistency (mean 0·7 (sd 0·97)) and test-retest reliability (mean 0·8 (sd 0·013)). CONCLUSIONS: The Dental Nutrition Knowledge Competency Scale is a validated and reliable instrument to assess nutrition knowledge related to dental health in low-income women.


Asunto(s)
Atención Odontológica/psicología , Caries Dental/psicología , Conocimientos, Actitudes y Práctica en Salud , Pobreza/psicología , Encuestas y Cuestionarios/normas , Adolescente , Adulto , Estudios Transversales , Análisis Factorial , Femenino , Humanos , Competencia Mental/psicología , Persona de Mediana Edad , Reproducibilidad de los Resultados , Texas , Adulto Joven
10.
Appl Opt ; 59(12): 3645-3651, 2020 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-32400480

RESUMEN

In response to the increasing demands of the capacity enhancement of optical communication, a compact and high-performance silicon mode division multiplexer is proposed that multiplexes the fundamental and first-order transverse magnetic modes. The device structure is based on an asymmetric bent directional coupler with an ultrasmall coupling length of 3.67 µm. Utilizing single-layer silicon waveguides with the same heights allows the proposed device to be fabricated using a single-step CMOS-compatible fabrication process, which provides a cost-effective design in comparison with the previously reported structures. The three-dimensional finite-difference time-domain simulation results confirm that the device has a low loss of 0.87 dB, low crosstalk of ${-}{21.8}\;{\rm dB}$-21.8dB, and high mode conversion efficiency of 98.3% at the communication wavelength of 1.55 µm. Furthermore, the device shows a broad bandwidth of about 110 nm, completely covering the C and L bands with crosstalk less than ${-}{10}\;{\rm dB}$-10dB. Moreover, it is shown that the proposed mode (de)multiplexer is fabrication tolerant for the coupling gap variation of ${-}{40}\;{\rm nm} \lt \Delta {g} \lt {23}\;{\rm nm}$-40nm<Δg<23nm and the waveguide width variation of ${-}{25}\;{\rm nm} \lt \Delta {W} \lt {25}\;{\rm nm}$-25nm<ΔW<25nm for a low loss of ${ \lt }- {1.67}\;{\rm dB}$<-1.67dB and low crosstalk of ${ \lt }- {10}\;{\rm dB}$<-10dB.

11.
Appl Opt ; 59(4): 975-984, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-32225234

RESUMEN

In this paper, a compact, broadband, and CMOS compatible ${2} \times {2}$2×2 optical switch based on hybrid plasmonic waveguides (HPWs) and curved directional coupler is presented. The proposed coupler consists of a combination of straight and curved hybrid plasmonic waveguides. By using the ability of HPWs for confining the light wave in a sub-wavelength scale and the curved structure to decrease the wavelength dependence of the directional coupler, a 3 dB power splitter with a ${3}\,\,\textrm{dB} \pm 0.5$3dB±0.5 bandwidth of about 410 nm and a footprint of ${7.6}\,\,\unicode{x00B5}\textrm{m} \times {2}\,\,\unicode{x00B5}\textrm{m}$7.6µm×2µm is achieved. By exploiting this optimal power splitter in a Mach-Zehnder interferometer structure, a ${2} \times {2}$2×2 electro-optic switch with a broad bandwidth of 400 nm and a small footprint of ${33}\,\,\unicode{x00B5}\textrm{m} \times {2.5}\,\,\unicode{x00B5}\textrm{m}$33µm×2.5µm is realized, which denotes the widest bandwidth compared to the previously reported similar structures. The three-dimensional finite-difference time-domain simulation results show a switching speed of 0.15 THz for the proposed optical switch, while the extinction ratio, power consumption, and insertion loss are 20 dB, 95.2 fJ/bit, and 4 dB, respectively, at the central wavelength of 1550 nm.

12.
J Mol Cell Cardiol ; 85: 207-14, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26073630

RESUMEN

Genome-wide association studies (GWAS) have identified genetic variants in a number of chromosomal regions that are associated with atrial fibrillation (AF). The mechanisms underlying these associations are unknown, but are likely to involve effects of the risk haplotypes on expression of neighbouring genes. To investigate the association between genetic variants at AF-associated loci and expression of nearby candidate genes in human atrial tissue and peripheral blood. Right atrial appendage (RAA) samples were collected from 122 patients undergoing cardiac surgery, of these, 12 patients also had left atrial appendage samples taken. 22 patients had a history of AF. Peripheral blood samples were collected from 405 patients undergoing diagnostic cardiac catheterisation. In order to tag genetic variation at each of nine loci, a total of 367 single nucleotide polymorphisms (SNPs) were genotyped using the Sequenom platform. Total expression of 16 candidate genes in the nine AF-associated regions was measured by quantitative PCR. The relative expression of each allele of the candidate genes was measured on the Sequenom platform using one or more transcribed SNPs to distinguish between alleles in heterozygotes. We tested association between the SNPs of interest and gene expression using total gene expression (integrating cis and trans acting sources of variation), and allelic expression ratios (specific for cis acting influences), in atrial tissue and peripheral blood. We adjusted for multiple comparisons using a Bonferroni approach. In subsidiary analyses, we compared the expression of candidate genes between patients with and without a history of AF. Total expression of 15 transcripts of 14 genes and allelic expression ratio of 14 transcripts of 14 genes in genomic regions associated with AF were measured in right atrial appendage tissue. 8 of these transcripts were also expressed in peripheral blood. Risk alleles at AF-associated SNPs were associated in cis with an increased expression of PITX2a (2.01-fold, p=6.5×10(-4)); and with decreased expression of MYOZ1 (0.39 fold; p=5.5×10(-15)), CAV1 (0.89 fold; p=5.9×10(-8)), C9orf3 (0.91 fold; 1.5×10(-5)), and FANCC (0.94-fold; p=8.9×10(-8)) in right atrial appendage. Of these five genes, only CAV1 was expressed in peripheral blood; association between the same AF risk alleles and lower expression of CAV1 was confirmed (0.91 fold decrease; p=4.2×10(-5)). A history of AF was also associated with a decrease in expression of CAV1 in both right and left atria (0.84 and 0.85 fold, respectively; p=0.03), congruent with the magnitude of the effect of the risk SNP on expression, and independent of genotype. The analyses in peripheral blood showed association between AF risk SNPs and decreased expression of KCNN3 (0.85-fold; p=2.1×10(-4)); and increased expression of SYNE2 (1.12-fold; p=7.5×10(-24)); however, these associations were not detectable in atrial tissue. We identified novel cis-acting associations in atrial tissue between AF risk SNPs and increased expression of PITX2a/b; and decreased expression of CAV1 (an association also seen in peripheral blood), C9orf3 and FANCC. We also confirmed a previously described association between AF risk variants and MYOZ1 expression. Analyses of peripheral blood illustrated tissue-specificity of cardiac eQTLs and highlight the need for larger-scale genome-wide eQTL studies in cardiac tissue. Our results suggest novel aetiological roles for genes in four AF-associated genomic regions.


Asunto(s)
Aminopeptidasas/metabolismo , Fibrilación Atrial/genética , Proteínas Portadoras/metabolismo , Caveolina 1/metabolismo , Proteína del Grupo de Complementación C de la Anemia de Fanconi/metabolismo , Proteínas de Homeodominio/metabolismo , Proteínas Musculares/metabolismo , Factores de Transcripción/metabolismo , Aminopeptidasas/genética , Fibrilación Atrial/metabolismo , Proteínas Portadoras/genética , Caveolina 1/genética , Proteína del Grupo de Complementación C de la Anemia de Fanconi/genética , Expresión Génica , Regulación de la Expresión Génica , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Atrios Cardíacos/metabolismo , Proteínas de Homeodominio/genética , Humanos , Proteínas Musculares/genética , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Factores de Riesgo , Factores de Transcripción/genética , Proteína del Homeodomínio PITX2
13.
Nutrients ; 16(2)2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38257168

RESUMEN

This research comprehensively examines 88 infant formulas available in the US market, with an emphasis on their diverging nutritional attributes based on lactose content. We stratified formulas into three categories: lactose-free, lactose-reduced, and entirely lactose-based. The formulas' nutritional content for 58 nutrients was obtained from the Nutrition Data System for Research (NDSR). Nutritional analysis revealed significant differences in nutrient composition across formula categories. For example, the results showed significant associations between the lactose content and glycemic index (GI) of the formula as well as 25 other nutrients. Specifically, we showed that for every gram of lactose per 100 g of formula that is removed, there was a 10.1% increase in GI (ß = -10.12, p ≤ 0.000), a 19%,5%, and a 2% increase in added sugar (ß = -0.19, p < 0.01), protein (ß = -0.05, p < 0.001), and polyunsaturated fatty acids (ß = -0.01, p < 0.01). The substitution of lactose in infant formulas significantly alters their nutritional profile, inducing changes in GI, added sugar, protein, and polyunsaturated fatty acids. These modifications have potential consequences for infant growth and metabolic responses and could influence long-term health trajectories. The clinical relevance of the composition differences between formulas should be further explored.


Asunto(s)
Fórmulas Infantiles , Lactosa , Lactante , Humanos , Nutrientes , Índice Glucémico , Ácidos Grasos Insaturados
14.
J Cosmet Dermatol ; 23(4): 1205-1216, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38059697

RESUMEN

BACKGROUND: Botulinum toxin has been widely and mainly used for the treatment of conditions affecting the upper and middle face; however, recent efforts have expanded the indications of botulinum toxin injection to the lower face and neck areas for cosmetic and medical purposes. AIMS: We have reviewed the latest updates on using botulinum toxin in the lower face and neck focusing on cosmetic purposes and have discussed the existing concerns as well as the adverse sequelae of these newer indications. PATIENTS/METHODS: A comprehensive literature search was performed using the following keywords [[botulinum] AND [[Toxin] OR [Neurotoxin]]] AND [[Lower AND Face] AND/OR [Neck]] within the main databases including Web of Science, PubMed, Embase and gray literature on and before February 2023. The data were screened using titles and abstracts and those relevant to the topic were included in the paper. RESULTS: Botulinum toxin injection has considerable cosmetic and therapeutic effect on facial contouring, masseteric hypertrophy, lower face and neck scars, gummy smile, drooping lip corner and even skin rejuvenation. CONCLUSION: BNT injection has been widely used for the treatment of different medical and cosmetic purposes. Low rates of side effects, which were self-limited in most cases, have been reported in the literature, making BNT a safe therapeutic medication in most cases. However, regulatory status needs to be updated and more accurately revised in many countries and more comprehensive research is required to address the existing gaps in this area including the site, dosage, and method of injection in each case.


Asunto(s)
Toxinas Botulínicas Tipo A , Fármacos Neuromusculares , Humanos , Estética Dental , Encía , Sonrisa , Neurotoxinas
15.
ACS Synth Biol ; 13(1): 168-182, 2024 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-38141039

RESUMEN

Identification of metabolic engineering targets is a fundamental challenge in strain development programs. While high-throughput (HTP) genetic engineering methodologies capable of generating vast diversity are being developed at a rapid rate, a majority of industrially interesting molecules cannot be screened at sufficient throughput to leverage these techniques. We propose a workflow that couples HTP screening of common precursors (e.g., amino acids) that can be screened either directly or by artificial biosensors, with low-throughput targeted validation of the molecule of interest to uncover nonintuitive beneficial metabolic engineering targets and combinations hereof. Using this workflow, we identified several nonobvious novel targets for improving p-coumaric acid (p-CA) and l-DOPA production from two large 4k gRNA libraries each deregulating 1000 metabolic genes in the yeast Saccharomyces cerevisiae. We initially screened yeast cells transformed with gRNA library plasmids for individual regulatory targets improving the production of l-tyrosine-derived betaxanthins, identifying 30 targets that increased intracellular betaxanthin content 3.5-5.7 fold. Hereafter, we screened the targets individually in a high-producing p-CA strain, narrowing down the targets to six that increased the secreted titer by up to 15%. To investigate whether any of the six targets could be additively combined to improve p-CA production further, we created a gRNA multiplexing library and subjected it to our proposed coupled workflow. The combination of regulating PYC1 and NTH2 simultaneously resulted in the highest (threefold) improvement of the betaxanthin content, and an additive trend was also observed in the p-CA strain. Lastly, we tested the initial 30 targets in a l-DOPA producing strain, identifying 10 targets that increased the secreted titer by up to 89%, further validating our screening by proxy workflow. This coupled approach is useful for strain development in the absence of direct HTP screening assays for products of interest.


Asunto(s)
Ingeniería Metabólica , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ingeniería Metabólica/métodos , Levodopa/metabolismo , ARN Guía de Sistemas CRISPR-Cas , Tirosina/genética , Tirosina/metabolismo
16.
Obesity (Silver Spring) ; 32(5): 979-988, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38600046

RESUMEN

OBJECTIVE: This study explores the impact of maternal pre-pregnancy BMI on infant neurodevelopment at 24 months in low-income Latino families. It also investigates whether infant diet mediates this relationship. METHODS: Latino mother-infant pairs (n = 163) were enrolled at 1 month post partum and were followed for 2 years, with assessments at 6-month intervals. Maternal pre-pregnancy anthropometrics were self-reported at baseline, and child neurodevelopment was assessed at 24 months using the Bayley Scales of Infant Development. Diet quality of infants was measured using the Healthy Eating Index (HEI)-2015 and HEI-Toddlers-2020 scores at multiple time points. Mediation and regression models that adjust for maternal factors were used to examine the associations. RESULTS: Pre-pregnancy BMI showed significant negative associations with child cognitive scores (ß = -0.1, 95% CI: -0.2 to -0.06, p < 0.001) and language scores (ß = -0.1, 95% CI: -0.2 to -0.03, p = 0.01) at 24 months. Infant HEI-2015 scores at 24 months partly mediated these associations, explaining 23% and 30% of the total effect on cognitive and language subscales, respectively. No specific dietary components in infants mediated the relationship, except for the total HEI-2015 score. CONCLUSIONS: Managing maternal obesity pre-pregnancy is crucial for improving infant neurodevelopmental outcomes, especially in low-income Latino families. Promoting healthy weight and enhancing infant diet quality can enhance neurodevelopment in these populations.


Asunto(s)
Índice de Masa Corporal , Desarrollo Infantil , Hispánicos o Latinos , Obesidad Materna , Adulto , Femenino , Humanos , Lactante , Masculino , Embarazo , Cognición , Dieta , Dieta Saludable , Hispánicos o Latinos/estadística & datos numéricos , Madres/psicología , Pobreza
17.
PLoS One ; 19(2): e0297235, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38349929

RESUMEN

OBJECTIVES: Caffeine's potential benefits on multiple sclerosis (MS), as well as on the ambulatory performance of non-MS populations, prompted us to evaluate its potential effects on balance, mobility, and health-related quality of life (HR-QoL) of persons with MS (PwMS). METHODS: This single-arm pilot clinical trial consisted of a 2-week placebo run-in and a 12-week caffeine treatment (200 mg/day) stage. The changes in outcome measures during the study period (weeks 0, 2, 4, 8, and 12) were evaluated using the Generalized Estimation Equation (GEE). The outcome measures were the 12-item Multiple Sclerosis Walking Scale (MSWS-12) for self-reported ambulatory disability, Berg Balance Scale (BBS) for static and dynamic balance, Timed Up and Go (TUG) for dynamic balance and functional mobility, Multiple Sclerosis Impact Scale (MSIS-29) for patient's perspective on MS-related QoL (MS-QoL), and Patients' Global Impression of Change (PGIC) for subjective assessment of treatment efficacy. GEE was also used to evaluate age and sex effect on the outcome measures over time. (Iranian Registry of Clinical Trials, IRCT2017012332142N1). RESULTS: Thirty PwMS were included (age: 38.89 ± 9.85, female: 76.7%). Daily caffeine consumption significantly improved the objective measures of balance and functional mobility (BBS; P-value<0.001, and TUG; P-value = 0.002) at each study time point, and the subjective measure of MS-related QoL (MSIS-29; P-value = 0.005) two weeks after the intervention. Subjective measures of ambulatory disability (MSWS-12) and treatment efficacy (PGIC) did not significantly change. The effect of age and sex on the outcome measures were also assessed; significant sex-time interaction effects were found for MSWS-12 (P-value = 0.001) and PGIC (P-value<0.001). The impact of age on BBS scores increased as time progressed (P-value = 0.006). CONCLUSIONS: Caffeine may enhance balance, functional mobility, and QoL in PwMS. Being male was associated with a sharper increase in self-reported ambulatory disability over time. The effects of aging on balance get more pronounced over time. TRIAL REGISTRATION: This study was registered with the Iranian Registry of Clinical Trials (Registration number: IRCT2017012332142N1), a Primary Registry in the WHO Registry Network.


Asunto(s)
Esclerosis Múltiple , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cafeína/uso terapéutico , Ingestión de Alimentos , Irán , Equilibrio Postural , Calidad de Vida , Caminata , Proyectos Piloto
18.
Nutrients ; 16(12)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38931150

RESUMEN

Growing evidence indicates that human milk oligosaccharides (HMOs) are important bioactive compounds that enhance health and developmental outcomes in breastfed babies. Maternal dietary intake likely contributes to variation in HMO composition, but studies identifying diet-HMO relationships are few and inconsistent. This study aimed to investigate how the maternal intake of macronutrients and micronutrients-specifically proteins, fats, vitamins, and minerals-associated with HMOs at 1 month (n = 210), 6 months (n = 131), and 12 months postpartum (n = 84). Several associations between maternal dietary factors and HMO profiles were identified utilizing partial correlation analysis. For example, maternal free sugar (rho = -0.02, p < 0.01), added sugar (rho = -0.22, p < 0.01), and sugary sweetened beverage (rho = -0.22, p < 0.01) intake were negatively correlated with the most abundant HMO, 2'-fucosyllactose (2'-FL), at 1 month, suggesting that higher sugar consumption was associated with reduced levels of 2'-FL. Further, vitamins D, C, K, and the minerals zinc and potassium were positively correlated with 2'-FL at 1 month (pAll < 0.05). For the longitudinal analysis, a mixed-effects linear regression model revealed significant associations between maternal vitamin intake and HMO profiles over time. For example, for each unit increase in niacin intake, there was a 31.355 nmol/mL increase in 2'-FL concentration (p = 0.03). Overall, the results provide additional evidence supporting a role for maternal nutrition in shaping HMO profiles, which may inform future intervention strategies with the potential of improving infant growth and development through optimal HMO levels in mothers' milk.


Asunto(s)
Dieta , Hispánicos o Latinos , Fenómenos Fisiologicos Nutricionales Maternos , Leche Humana , Oligosacáridos , Humanos , Leche Humana/química , Femenino , Oligosacáridos/análisis , Adulto , Adulto Joven , Lactante , Lactancia Materna , Trisacáridos/análisis , Vitaminas/análisis , Vitaminas/administración & dosificación , Estudios Longitudinales , Madres
19.
Expert Rev Med Devices ; 20(6): 433-447, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37042425

RESUMEN

INTRODUCTION: Migraine is a prevalent, inherited and disabling brain disease with multiple symptoms and a variety of treatment options. Nerivio, utilizing remote electrical neuromodulation (REN) a wearable device, offers users good efficacy, tolerability and safety. It is user-friendly, affordable, non-addictive and cleared by the FDA and the European Conformity. AREAS COVERED: The device structure, mechanism of action, indications for use, application instructions, efficacy, adverse events, tolerability, safety, patient satisfaction, associated application and the research highlights are discussed herein. EXPERT OPINION: The device works well for most people living with migraine, often without concomitant medication, is tolerable, safe and causes minimal and mild adverse effects. It expands our migraine treatment options and improves patient adherence to treatment. Nerivio is easy-to-use and can be worn at any time of the day; it provides a non-pharmacologic option for the optimization of migraine treatment without significant adverse events.


Asunto(s)
Trastornos Migrañosos , Humanos , Resultado del Tratamiento , Trastornos Migrañosos/prevención & control , Satisfacción del Paciente , Cooperación del Paciente
20.
Clin Case Rep ; 11(11): e8109, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38028097

RESUMEN

Key Clinical Message: Although increasing in number, cases of CVS are being frequently misdiagnosed and many are refractory to the available treatments. This paper draws attention to a timely consideration of this disorder upon suspicion and proposes rectal diazepam and cinnarizine as highly effective treatments in refractory cases of CVS. Abstract: Cyclic vomiting syndrome (CVS) is a set of recurrent episodic attacks of nausea and vomiting. This is a migraine-related disorder that mostly affects children. Several medications have been recommended for abortive and prophylactic treatment. Unfortunately, in some cases, the treatment is not completely effective and affects the quality of life of the sufferer. In this paper, we report on two cases of children experiencing refractory CVS attacks who were not responsive to recommended medications for acute phase and prophylaxis. This account highlights the efficacy of rectal diazepam for the acute phase of CVS and cinnarizine, an anti-migraine and anti-histamine agent, for prophylaxis of further attacks.

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