RESUMO
Asians are underrepresented across many omics databases, thereby limiting the potential of precision medicine in nearly 60% of the global population. As such, there is a pressing need for multi-omics derived quantitative trait loci (QTLs) to fill the knowledge gap of complex traits in populations of Asian ancestry. Here, we provide the first blood-based multi-omics analysis of Asian pregnant women, constituting high-resolution genotyping (N = 1079), DNA methylation (N = 915) and transcriptome profiling (N = 238). Integrative omics analysis identified 219 154 CpGs associated with cis-DNA methylation QTLs (meQTLs) and 3703 RNAs associated with cis-RNA expression QTLs (eQTLs). Ethnicity was the largest contributor of inter-individual variation across all omics datasets, with 2561 genes identified as hotspots of this variation; 395 of these hotspot genes also contained both ethnicity-specific eQTLs and meQTLs. Gene set enrichment analysis of these ethnicity QTL hotspots showed pathways involved in lipid metabolism, adaptive immune system and carbohydrate metabolism. Pathway validation by profiling the lipidome (~480 lipids) of antenatal plasma (N = 752) and placenta (N = 1042) in the same cohort showed significant lipid differences among Chinese, Malay and Indian women, validating ethnicity-QTL gene effects across different tissue types. To develop deeper insights into the complex traits and benefit future precision medicine research in Asian pregnant women, we developed iMOMdb, an open-access database.
Assuntos
Gestantes , Locos de Características Quantitativas , Povo Asiático/genética , Feminino , Humanos , Lipídeos , Gravidez , Locos de Características Quantitativas/genética , RNARESUMO
PURPOSE: Vitamin A deficiency (VAD) remains a significant contributor to childhood morbidity and mortality in developing countries; therefore, the implementation of sustainable and cost-effective approaches to control VAD is of utmost pertinence. This study aims to investigate the efficacy of red palm olein (RPO)-enriched biscuit supplementation in improving vitamin A, haematological, iron, and inflammatory status among vitamin A-deficient schoolchildren. METHODS: We conducted a double-blinded, randomised controlled trial involving 651 rural primary schoolchildren (8-12 years) with VAD in Malaysia. The schoolchildren were randomised to receive either RPO-enriched biscuits (experimental group, n = 334) or palm olein-enriched biscuits (control group, n = 317) for 6-month duration. RESULTS: Significant improvements in retinol and retinol-binding protein 4 levels were observed in both groups after supplementation (P < 0.001). The improvement in retinol levels were similar across groups among subjects with confirmed VAD (P = 0.40). Among those with marginal VAD, greater improvement in retinol levels was recorded in the control group (P < 0.001) but lacked clinical significance. The levels of α- and ß-carotenes, haematological parameters (haemoglobin, packed cell volume, mean corpuscular volume and mean corpuscular haemoglobin) and iron enhanced more significantly in the experimental group (P < 0.05). The significant reduction in the prevalence of microcytic anaemia (- 21.8%) and high inflammation (- 8.1%) was only observed in the experimental group. CONCLUSION: The supplementation of RPO-enriched biscuits enhanced levels of provitamin A carotenes, iron, and erythropoiesis, and exhibited anti-inflammatory effects. Therefore, the incorporation of RPO into National Nutritional Intervention Programs may be a potential measure to improve the health status of vitamin A-deficient children, among various other interventions. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03256123).
Assuntos
Deficiência de Vitamina A , Vitamina A , Criança , Humanos , Carotenoides , Provitaminas , Ferro , Eritropoese , Deficiência de Vitamina A/tratamento farmacológico , Deficiência de Vitamina A/epidemiologia , Suplementos Nutricionais , Estado NutricionalRESUMO
PURPOSE: Biofilms are a significant cause of morbidity in patients with indwelling medical devices. Biofilms pose a potential risk with reusable inner cannulas by increasing the risk of infections. Effective decontamination is thus vital in decreasing bioburden. The current guidelines for cleaning inner cannulas are varied, with multiple techniques being recommended, which are not supported by strong evidence. This randomized, controlled, cross-over study attempted to enumerate the bacterial count of inner cannulas used in tracheostomy patients (n = 60) pre-and post-decontamination with detergent (A) or sterile water (B). MATERIALS AND METHODS: The patients were randomly allocated to sequence A > B or B > A in 1:1 fashion. The saline flushing of the inner cannulas was plated on trypticase soy agar with 5 % sheep blood to enumerate the bacterial count. RESULTS: The mean ratio [Log (CFU)post/Log (CFU)pre]A/[Log (CFU)post/Log (CFU)pre]B based on 53 samples was 0.918 ± 0.470, two-sided 90 % confidence interval (CI) 0.812, 1.024. The equivalence criterion was met as the mean ratio after cleaning fell within the equivalence region of 0.8 and 1.25. CONCLUSION: This study demonstrated the microbiological efficacy of both detergent and sterile water in the decontamination of inner cannulas, and that sterile water was not less effective than detergent in reducing the bacterial load for safe re-use of inner cannulas. This has the potential to promote cost savings for patients with tracheostomy, both in the hospital and the community. The study findings may also be relevant in formulating tracheostomy care policies.
Assuntos
Cânula , Traqueostomia , Humanos , Contagem de Colônia Microbiana , Estudos Cross-Over , Detergentes , ÁguaRESUMO
BACKGROUND: Auricularia auricula is rich in bioactive components, and microbial fermentation can further dramatically increase its content and bioavailability. However, there are few studies on the relationship between fermented A. auricula pulp (FAAP) and gut microbiota. In this study, standard strains Lactobacillus plantarum 21801 and 21805 purchased from the China Center of Industrial Culture Collection were used to ferment A. auricula pulp at a ratio of 2:1, with an inoculum of 5%, a fermentation temperature of 31 °C, and a fermentation time of 22 h. The nutritional properties, aroma, and color of FAAP and their effects on the body characteristics of mice and the structure and abundance of gut microbiota are discussed. RESULTS: The results showed that, compared with A. auricula pulp, FAAP significantly increased the nutritional properties while maintaining favorable sensory quality and flavor profiles. Among them, the content of total polyphenols and total flavonoids reached 22.04 µg mL-1 and 20.56 µg mL-1 respectively, and the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid free-radical scavenging rate increased to 73.21%. The consumption of FAAP had no negative effects on weight or liver and kidney function in mice and dramatically enhanced the antioxidant capacity in the liver and serum. The production of short-chain fatty acids in the gut was promoted, the relative abundance of beneficial bacteria (Lactobacillus, Bifidobacterium, norank_f__Muribaculaceae and unclassified_f__Lachnospiraceae) increased, and the growth of some pathogenic bacteria (Helicobacter, Mucispirillum, and Alloprevotella) was inhibited. CONCLUSION: These findings demonstrate that FAAP is rich in nutrients and has unique functional properties that promote host health and regulate the gut microbiota. © 2023 Society of Chemical Industry.
Assuntos
Auricularia , Microbioma Gastrointestinal , Lactobacillus , Lactobacillus/metabolismo , Antioxidantes/metabolismo , Polifenóis/farmacologia , Bactérias , FermentaçãoRESUMO
Emerging evidence has suggested that circular RNAs (circRNAs) have vital functions during the initiation and progression of various diseases. However, circRNA potential mechanisms in colorectal cancer (CRC) are largely unknown. Here, we sought to investigate the role and underlying regulatory mechanism of circ0104103 in CRC. circ0104103 was validated by quantitative RT-PCR (qRT-PCR) and Sanger sequencing. Gain- and loss-of-function assays in cell lines and mouse xenograft models were utilized to investigate the effects of circ0104103 in CRC. RNA pull-down assays, RNA immunoprecipitation assays, bioinformatics analyses, RNA FISH, and luciferase reporter assays were used to elucidate the potential mechanism of circ0104103 in CRC. We identified circ0104103, which is strongly downregulated in CRC tissues and cell lines. Functional studies revealed that circ0104103 inhibited CRC cell growth, migration, and invasion both in vitro and in vivo. Mechanistically, circ0104103 binds to HuR, a functional RNA-binding protein commonly expressed in CRC. HuR binds to the 3'UTR of LACTB mRNA to facilitate stabilization and increase its expression. Moreover, circ0104103 was verified as a competing endogenous RNA (ceRNA) via negative regulation of miR-373-5p to increase LACTB expression, resulting in inhibiting the occurrence and progression of CRC. Taken together, our study revealed that circ0104103 acts as a tumor suppressor and may be a novel biomarker and therapeutic target in CRC.
Assuntos
Neoplasias Colorretais , Proteína Semelhante a ELAV 1 , MicroRNAs , RNA Circular , Animais , Humanos , Camundongos , beta-Lactamases/genética , beta-Lactamases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/genética , Proteínas de Membrana/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Mitocondriais/metabolismo , Interferência de RNA , RNA Circular/genética , Proteína Semelhante a ELAV 1/genética , Proteína Semelhante a ELAV 1/metabolismoRESUMO
Childhood malnutrition is known as a public health concern globally. The present study aims to assess the anthropometry and blood biochemical status of rural primary schoolchildren in Malaysia. A total of 776 children (7-11 years old) from ten rural primary schools from five states were included in this study. Nutritional outcomes were assessed based on sex, age group and school categories among the children (median age: 9 years (P25:8, P75:10)). The overall prevalence of malnutrition was 53·4 %. Vitamin A deficiency (VAD) was recorded at 20·6 and 39·8 % based on retinol and retinol-binding protein (RBP) levels, respectively. Anaemia, iron deficiency (ID), iron-deficiency anaemia (IDA) and elevated inflammation were found at 14·9, 17·9, 9·1 and 11·5 %, respectively. Malnutrition, VAD, anaemia, ID, IDA and elevated inflammation were more prevalent among Orang Asli (OA) schoolchildren compared with Non-Orang Asli schoolchildren. Higher occurrences of VAD and anaemia were also found among children aged <10 years. Retinol, RBP, α-carotene, ferritin and haemoglobin levels were lower among undernourished children. Besides, overweight/obese children exhibited a higher level of high-sensitivity C-reactive protein. Multivariate analysis demonstrated that OA school children (adjusted OR (AOR): 6·1; 95 % CI 4·1, 9·0) and IDA (AOR: 3·6; 95 % CI 1·9, 6·6) were associated with stunting among this population. The present study revealed that malnutrition, micronutrient deficiencies and anaemia are prevalent among rural primary schoolchildren in Malaysia, especially those from OA schools and younger age children (<10 years). Hence, more appropriate and targeted measures are needed to improve the nutritional status of these children.
Assuntos
Anemia Ferropriva , Anemia , Deficiências de Ferro , Desnutrição , Obesidade Infantil , Deficiência de Vitamina A , Criança , Humanos , Deficiência de Vitamina A/epidemiologia , Vitamina A , Prevalência , Malásia/epidemiologia , Desnutrição/epidemiologia , Anemia Ferropriva/epidemiologia , Estado Nutricional , Anemia/epidemiologia , Anemia/etiologia , Inflamação , Instituições AcadêmicasRESUMO
BACKGROUND: The anion gap (AG) is often used to evaluate acid-base disorders. The reference interval for normal AG is used to differentiate between raised (gap) or normal AG (non-gap) acidosis. Historically accepted AG values may not be valid with the evolution of modern analytical techniques and the reference interval requires revalidation. AIMS: To determine the reference interval for AG based on current laboratory techniques. METHODS: During a health-screening exercise, 284 participants with no major illnesses volunteered surplus blood for analysis. The samples were tested in an internationally accredited clinical laboratory. AG was calculated by [Na+ ] - [Cl- ] - [HCO3 - ] and AGK by [Na+ ] + [K+ ] - [Cl- ] - [HCO3 - ]. The reference interval was determined at 2.5th-97.5th percentiles. Analysis was further undertaken for a subcohort of 156 individuals with no suboptimal health indicators. RESULTS: Median age was 35 years, body mass index 23.4 kg/m2 and the glomerular filtration rate was 106 mL/min/1.73 m2 . Median AG was 13 mmol/L and the reference interval for normal AG is 10-18 mmol/L with a 99% level of confidence. Statistically significant differences in AG were detected for sex, race, obesity and serum albumin, but the difference was 1 mmol/L between subgroups. The reference interval was the same for the sub-cohort of 156 individuals. Median AGK was 17.7 mmol/L and reference interval was 14.6-22.5 mmol/L. CONCLUSIONS: The AG reference interval of 10-18 mmol/L is valid for laboratories with similar reference intervals for electrolytes. Lower values expected with current laboratory techniques were not observed. The median AG of 13 mmol/L may be used to differentiate gap acidosis, non-gap acidosis or mixed acid-base disorders.
Assuntos
Equilíbrio Ácido-Base , Acidose , Adulto , Eletrólitos , Humanos , Valores de Referência , Albumina Sérica/análiseRESUMO
Songs are commonly used in educational public health programmes to facilitate the understanding of health messages. During the COVID-19 pandemic, national blood banks witnessed a pronounced reduction in blood donors. Thus, we created a song with the title 'Keep the World Beating' to raise awareness of the need for blood and to promote blood donation. To maximise participation, we carried out a live broadcast of the donation process and the music video on social media, increasing visibility and accessibility to the event. The number of donations increased in the month after the song was released. Songs can be used to strengthen current entertainment-education strategies promoting blood donation and to increase the level of awareness among the local population, thus motivating people to donate blood in a time of need.
RESUMO
3D cellular spheroids/microcarriers (100 µm-1 mm) are widely used in biomanufacturing, and non-invasive biosensors are useful to monitor cell quality in bioprocesses. In this work, a novel microfluidic approach for label-free and continuous-flow monitoring of single spheroid/microcarrier (hydrogel and Cytodex) based on electrical impedance spectroscopy using co-planar Field's metal electrodes is reported. Through numerical simulation and experimental validation, two unique impedance signatures (|ZLF | (60 kHz), |ZHF | (1 MHz)) which are optimal for spheroid growth and viability monitoring are identified. Using a closed-loop recirculation system, it is demonstrated that |ZLF | increases with breast cancer (MCF-7) spheroid biomass, while higher opacity (impedance ratio |ZHF |/|ZLF |) indicates cell death due to compromised cell membrane. Anti-cancer drug (paclitaxel)-treated spheroids also exhibit lower |ZLF | with increased cell dissociation. Interestingly, impedance characterization of adipose-derived mesenchymal stem cell differentiation on Cytodex microcarriers reveals that adipogenic cells (higher intracellular lipid content) exhibit higher impedance than osteogenic cells (more conductive due to calcium ions) for both microcarriers and single cell level. Taken together, the developed platform offers great versatility for multi-parametric analysis of spheroids/microcarriers at high throughput (≈1 particle/s), and can be readily integrated into bioreactors for long-term and remote monitoring of biomass and cell quality.
Assuntos
Células-Tronco Mesenquimais , Microfluídica , Diferenciação Celular , Impedância Elétrica , Esferoides CelularesRESUMO
CONTEXT: Studies find surgery superior to medications in the treatment of primary aldosteronism (PA). It would be ideal to compare surgical and medical therapy in patients with unilateral PA only, who have the option between these treatment modalities. However, this is challenging as most patients with unilateral PA on adrenal vein sampling (AVS) undergo surgery. OBJECTIVE: To compare outcomes of surgery and medications in patients with confirmed or likely unilateral PA. DESIGN: Retrospective cohort study of 274 patients with PA managed at two referral centres from 2000 to 2019. PATIENTS: 154 patients identified with unilateral PA using AVS and a validated clinical prediction model were treated with surgical (n = 86) or medical (n = 68) therapy. MEASUREMENTS: Primary outcome was a composite incident cardiovascular event comprising acute myocardial infarction, coronary revascularization, stroke, atrial fibrillation or congestive cardiac failure. Secondary outcomes were clinical and biochemical control. RESULTS: Cardiovascular outcomes were comparable, with the surgery group having an adjusted hazard ratio of 0.93 (95% CI: 0.32-2.67), p = .89. Both treatments improved clinical and biochemical control, but surgery resulted in better systolic blood pressure, 133.0 ± 11.7 mmHg versus 137.9 ± 14.6 mmHg, p = .02, and lower defined daily dosages of antihypertensive medications, 1.0 (IQR 0.0-2.0) versus 2.6 (IQR 0.8-4.3), p < .001. In addition, 12 of 86 patients in the surgery group failed medical therapy before opting for surgery. CONCLUSION: In patients with unilateral PA who can tolerate medications, medical therapy improves clinical and biochemical control, and may offer similar cardiovascular protection. However, surgery reduces pill burden, may cure hypertension and is recommended for unilateral PA.
Assuntos
Hiperaldosteronismo , Modelos Estatísticos , Glândulas Suprarrenais , Adrenalectomia , Humanos , Hiperaldosteronismo/tratamento farmacológico , Hiperaldosteronismo/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
In this work, we aim to observe and study the physics of bacteria and cancer cells pearl chain formation under dielectrophoresis (DEP). Experimentally, we visualized the formation of Bacillus subtilis bacterial pearl chain and human breast cancer cell (MCF-7) chain under positive and negative dielectrophoretic force, respectively. Through a simple simulation with creeping flow, AC/DC electric fields, and particle tracing modules in COMSOL, we examined the mechanism by which bacteria self-organize into a pearl chain across the gap between two electrodes via DEP. Our simulation results reveal that the region of greatest positive DEP force shifts from the electrode edge to the leading edge of the pearl chain, thus guiding the trajectories of free-flowing particles toward the leading edge via positive DEP. Our findings additionally highlight the mechanism why the free-flowing particles are more likely to join the existing pearl chain rather than starting a new pearl chain. This phenomenon is primarily due to the increase in magnitude of electric field gradient, and hence DEP force exerted, with the shortening gap between the pearl chain leading edge and the adjacent electrode. The findings shed light on the observed behavior of preferential pearl chain formation across electrode gaps.
Assuntos
Bactérias , Linhagem Celular Tumoral , Simulação por Computador , Eletrodos , Eletroforese , Desenho de Equipamento , Humanos , NeoplasiasRESUMO
We highlight two distinct cases of myocardial infarction occurring concurrently with anaphylaxis at our centre in Singapore. The first case had cardiac symptoms and electrocardiogram changes concomitant with his anaphylaxis presentation, suggestive of Kounis syndrome, while the second case presented with anaphylaxis and only developed cardiac symptoms and electrocardiogram changes after treatment with intramuscular epinephrine, suggestive of epinephrine-induced myocardial infarction. Both these conditions are uncommon and under-recognised, and we review the current literature to compare the similarities and differences in their clinical manifestations, pathophysiology, and management. Kounis syndrome occurs secondary to mast cell degranulation ultimately resulting in coronary vasospasm, platelet activation and inflammatory response, whereas epinephrine causes platelet aggregation. Therefore, treatment priorities of Kounis syndrome are treatment of allergy, treatment of vasospasm, and treatment with anti-platelet therapy and revascularization if coronary plaques are present. For epinephrine-induced myocardial infarction, after epinephrine treatment is discontinued, considerations in management are re-vascularisation or pharmacotherapy. Further research will help with better understanding of both conditions and formulation of clinical management guidelines.
Assuntos
Anafilaxia , Síndrome de Kounis , Infarto do Miocárdio , Anafilaxia/induzido quimicamente , Eletrocardiografia , Epinefrina , Humanos , Síndrome de Kounis/tratamento farmacológico , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológicoRESUMO
BACKGROUND: In October 2019, surgeons from Changi General Hospital (CGH) Breast Centre delivered a series of health talk for its employees to assess the knowledge and perception of breast cancer screening and to improve the level of related knowledge amongst the institution's healthcare workers. This was to enable CGH, a healthcare provider to not only care for our patients, but also to look after its staff. METHODS: 141 hospital staff attended a 40-min talk followed by an open question and answer forum. Pre and post talk surveys were conducted to gauge knowledge, attitudes, beliefs and misconceptions towards breast cancer screening and treatment. Question domains were divided into (1) breast cancer knowledge, (2) breast cancer screening guidelines and (3) attitudes and perception of breast cancer screening and treatment. Univariate and multivariate logistic regression analysis were used to examine the relationship between demographics and performance in question domains. RESULTS: The overall response rate was 131 out of a total of 141 attendees (92.9%). The median age was 44 years old (range, 22-67), with nursing staff making up 40% of the cohort. Analysis showed statistically significant improvement in median score across all 3 domains. (p < 0.05) after the forum. We found that respondents who were women ≥ 40 years (eligible age for screening), had higher income, lived in larger housing types, had attended previous talks, had served > 10 years in healthcare and had personal encounter with breast cancer patients performed better. Surprisingly, being a nurse or having a university degree did not translate to a better score. 99% of respondents found the forum beneficial and would recommend it to others. Several knowledge gaps about breast cancer screening and misconceptions were identified. Future campaigns should focus on raising awareness of the national screening program BreastScreen Singapore. We aim to reinforce its recommendations, promote on the affordability and ready accessibility. CONCLUSIONS: A simple Breast Cancer Awareness Month campaign targeted at healthcare workers was found to be effective at educating hospital staff on breast cancer, screening practices and improving perception of screening and treatment practices. This may empower them to not only care for themselves but also to serve patients better.
Assuntos
Neoplasias da Mama , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Criança , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Percepção , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The application of intra-operative blood salvage autotransfusion(IBSA) in liver transplantation(LT) for hepatocellular carcinoma(HCC) remains controversial due to the theoretical risk of tumour cell(TC) reintroduction. Current studies evaluating for presence of TC are limited by suboptimal detection techniques. This study aims to analyze the presence of TC in HCC LT autologous blood using microfluidics technology. METHODS: A prospective study of HCC patients who underwent LT from February 2018-April 2019 was conducted. Blood samples were collected peri-operatively. TCs were isolated using microfluidics technology and stained with antibody cocktails for confirmation. RESULTS: A total of 15 HCC LT patients were recruited. All recipients had tumour characteristics within the University of California, San Francisco(UCSF) criteria pre-operatively. TC was detected in all of the autologous blood samples collected from the surgical field. After IOCS wash, five patients had no detectable TC, while 10 patients had detectable TC; of these two remained positive for TC after Leukocyte Depletion Filter(LDF) filtration. CONCLUSION: The risk of tumour cell reintroduction using IBSA in HCC LT patients can be reduced with a single LDF. Future studies should evaluate the proliferation capacity and tumorigenicity of HCC TC in IBSA samples, and the effects of TC reintroduction in patients with pre-existing HCC TCs.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Recuperação de Sangue Operatório , Transfusão de Sangue Autóloga , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Microfluídica , Recidiva Local de Neoplasia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
OBJECTIVE: To develop and validate a questionnaire which evaluates the blood donors' satisfaction. BACKGROUND: In Malaysia, blood procurement relies mainly on voluntary non-remunerated donors. Hence, it is important to ensure the satisfaction of the blood donors in order to increase retention. METHODS: This study was conducted among blood donors who attended blood donation and understood the Malay language. Non-Malaysian and illiterate donors were excluded. The questionnaire was developed by the transfusion medicine team. Content validity was established by content reviewers, while face validity was examined in the cognitive debriefing stage. For the 18-item questionnaire, 90 respondents were required based on the 1:5 ratio. A retest was performed in two weeks' time. RESULTS: One hundred and thirty-seven participants responded in the first phase, while 103 responded after two weeks. The five domains were: technical, interpersonal, accessibility/ convenience, physical experience and overall satisfaction. The Kaiser-Meyer-Olkin (KMO) value was 0.896, with significant Bartlett's Test of Sphericity (P < 0.001). The factor loadings ranged from 0.729 to 0.953. The Cronbach alpha values of the five domains ranged from 0.814 to 0.955 and the intraclass correlation coefficient ranged from 0.663 to 0.847. CONCLUSION: The Malaysian blood donor's satisfaction (M-BDS) questionnaire is a reliable and valid tool suitable for the assessment of blood donor's satisfaction in blood donation centres.
RESUMO
In bacterial chemotaxis, chemoattractant molecules may bind either directly or indirectly with receptors within the cell periplasmic space. The indirect binding mechanism, which involves an intermediate periplasmic binding protein, has been reported to increase sensitivity to dilute attractant concentrations as well as range of response. Current mathematical models for bacterial chemotaxis at the population scale do not appear to take the periplasmic binding protein (BP) concentration or the indirect binding mechanics into account. We formulate an indirect binding extension to the existing Rivero equation for chemotactic velocity based on fundamental reversible enzyme kinetics. The formulated indirect binding expression accounts for the periplasmic BP concentration and the dissociation constants for binding between attractant and periplasmic BP, as well as between BP and chemoreceptor. We validate the indirect-binding model using capillary assay simulations of the chemotactic responses of E. coli to the indirectly-binding attractants maltose and AI-2. The predicted response agrees well with experimental data from a number of maltose capillary assay studies conducted in previous literature. The model is also able to achieve good agreement with AI-2 capillary assay data of one study out of two tested. The chemotactic response of E. coli towards AI-2 appears to be of higher complexity due to reports of variable periplasmic BP concentration as well as the low concentration of periplasmic BP relative to the total receptor concentration. Our current model is thus suitable for indirect binding chemotactic response systems with constant periplasmic BP concentration that is significantly larger than the total receptor concentration, such as the response of E. coli towards maltose. Further considerations may be taken into account to model the chemotactic response towards AI-2 with greater accuracy.
Assuntos
Quimiotaxia , Proteínas de Escherichia coli , Proteínas de Bactérias , Escherichia coli , Proteínas de MembranaRESUMO
PURPOSE: To explore the associations between type of milk feeding (the "nutrients") and mode of breast milk feeding (the "nursing") with child cognition. METHODS: Healthy children from the GUSTO (Growing Up in Singapore Toward healthy Outcomes) cohort participated in repeated neurodevelopmental assessments between 6 and 54 months. For "nutrients", we compared children exclusively bottle-fed according to type of milk received: formula only (n = 296) vs some/all breast milk (n = 73). For "nursing", we included only children who were fully fed breast milk, comparing those fed directly at the breast (n = 59) vs those fed partially/completely by bottle (n = 63). RESULTS: Compared to infants fed formula only, those who were bottle-fed breast milk demonstrated significantly better cognitive performance on both the Bayley Scales of Infant and Toddler Development (Third Edition) at 2 years [adjusted mean difference (95% CI) 1.36 (0.32, 2.40)], and on the Kaufman Brief Intelligence Test (Second Edition) at 4.5 years [7.59 (1.20, 13.99)]. Children bottle-fed breast milk also demonstrated better gross motor skills at 2 years than those fed formula [1.60 (0.09, 3.10)]. Among infants fully fed breast milk, those fed directly at the breast scored higher on several memory tasks compared to children bottle-fed breast milk, including the deferred imitation task at 6 months [0.67 (0.02, 1.32)] and relational binding tasks at 6 [0.41 (0.07, 0.74)], 41 [0.67 (0.04, 1.29)] and 54 [0.12 (0.01, 0.22)] months. CONCLUSIONS: Our findings suggest that nutrients in breast milk may improve general child cognition, while nursing infants directly at the breast may influence memory.
Assuntos
Alimentação com Mamadeira/estatística & dados numéricos , Aleitamento Materno/estatística & dados numéricos , Desenvolvimento Infantil/fisiologia , Cognição/fisiologia , Nutrientes/administração & dosagem , Adolescente , Adulto , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Leite Humano , Singapura , Adulto JovemRESUMO
BACKGROUND: Iron deficiency is the most prevalent nutrient deficiency and the most common cause of anaemia worldwide. Because of the increased iron requirements during pregnancy, iron deficiency can lead to maternal anaemia and reduced newborn iron stores. We examined the proportion and risk factors of iron deficiency among pregnant women in a developed Asian country. METHODS: Within a prospective cohort in Singapore, 985 Asian women were assessed for iron status at 26-28 weeks' gestation, with plasma ferritin and soluble transferrin receptor (sTfR) measurements. Iron status was determined according to plasma ferritin concentrations at ≥30 µg/L (iron sufficiency), 15 to < 30 µg/L (modest iron depletion) and < 15 µg/L (severe iron depletion). Multivariable ordinal logistic regression was used to analyze risk factors for modest and severe iron depletion. RESULTS: The median (25-75th percentile) plasma ferritin concentration was 24.2 (19.9-30.6) µg/L. Overall, 660 (67.0%) and 67 (6.8%) women had modest and severe iron depletion, respectively. Higher plasma sTfR was observed in women with severe iron depletion than among those with iron sufficiency (median 17.6 versus 15.5 nmol/L; p < 0.001). Age < 25 years (odds ratio 2.36; 95% confidence interval 1.15-4.84), Malay (2.05; 1.30-3.24) and Indian (1.98; 1.14-3.44) ethnicities (versus Chinese), university qualification (1.64; 1.13-2.38), multiparity (1.73; 1.23-2.44) and lack of iron-containing supplementation (3.37; 1.25-8.53) were associated with increased odds of modest and severe iron depletion. CONCLUSIONS: Nearly three-quarters of Singaporean women were iron deficient in the early third trimester of pregnancy. These results suggest universal screening and supplementation of at-risk pregnancies may be evaluated as a preventive strategy. TRIAL REGISTRATION: NCT01174875 . Registered 1 July 2010 (retrospectively registered).
Assuntos
Anemia Ferropriva/epidemiologia , Ferritinas/sangue , Ferro da Dieta/administração & dosagem , Complicações Hematológicas na Gravidez/epidemiologia , Adulto , Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Ferro/sangue , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/diagnóstico , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Receptores da Transferrina/sangue , Fatores de Risco , Singapura , Adulto JovemRESUMO
The evolutionarily conserved family of AP-2 transcription factors (TF) regulates proliferation, differentiation, and apoptosis. Mutations in human AP-2 TF have been linked with bronchio-occular-facial syndrome and Char Syndrome, congenital birth defects characterized by craniofacial deformities and patent ductus arteriosus, respectively. How mutations in AP-2 TF cause the disease phenotypes is not well understood. Here, we characterize the aptf-2(qm27) allele in Caenorhabditis elegans, which carries a point mutation in the conserved DNA binding region of AP-2 TF. We show that compromised APTF-2 activity leads to defects in dorsal intercalation, aberrant ventral enclosure and elongation defects, ultimately culminating in the formation of morphologically deformed larvae or complete arrest during epidermal morphogenesis. Using cell lineaging, we demonstrate that APTF-2 regulates the timing of cell division, primarily in ABarp, D and C cell lineages to control the number of neuroblasts, muscle and epidermal cells. Live imaging revealed nuclear enrichment of APTF-2 in lineages affected by the qm27 mutation preceding the relevant morphogenetic events. Finally, we found that another AP-2 TF, APTF-4, is also essential for epidermal morphogenesis, in a similar yet independent manner. Thus, our study provides novel insight on the cellular-level functions of an AP-2 transcription factor in development.
Assuntos
Anormalidades Múltiplas/genética , Caenorhabditis elegans/genética , Diferenciação Celular/genética , Permeabilidade do Canal Arterial/genética , Desenvolvimento Embrionário/genética , Face/anormalidades , Dedos/anormalidades , Fator de Transcrição AP-2/genética , Anormalidades Múltiplas/patologia , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas de Caenorhabditis elegans/genética , Linhagem da Célula/genética , Permeabilidade do Canal Arterial/patologia , Epiderme/crescimento & desenvolvimento , Face/patologia , Dedos/patologia , Humanos , Morfogênese/genética , Mutação , Células-Tronco Neurais/metabolismoRESUMO
BACKGROUND: This study investigated the in vivo prophylactic effect of probiotic chocolate on constipation. Rats were administered chocolate containing 2.5 × 1010 CFU g-1 of probiotics daily for 4 weeks and treated with loperamide (5 mg kg-1 ) daily at the fourth week of treatment. RESULTS: Probiotic chocolate treatment significantly (P < 0.05) increased the intestinal motility, colon length, fecal moisture content and number of excreted fecal pellets in constipated rats. Moreover, quantitative real-time polymerase chain reaction data and histological images also revealed that both probiotic chocolate LYC and BB12 treatments were capable of upregulating the mRNA expression levels of colonic ZO-1, occludin and AQP8, leading to the maintenance of the defensive barrier function in the constipated rats compared with the negative controls. Interestingly, these treatments also modulated gut bacterial populations by increasing the abundance levels of Lactobacillus and Bifidobacterium, as well as reducing the abundance level of Enterobacteriaceae. CONCLUSION: The present study demonstrated that probiotic chocolate LYC and BB12 could potentially be used as alternative agents for prophylactic constipation. © 2018 Society of Chemical Industry.