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Gel lubrication is routinely used during gynecological examination to prevent or reduce pain, yet its impact on microbial composition during sampling remains unclear. This study aimed to investigate whether lubricating gel affects the microbial composition of vaginal samples. We included 31 pregnant women presenting during their third trimester to clinics or emergency room and collected 143 unique vaginal samples for 16S amplicon microbial analysis. Vaginal samples were obtained using sterile swabs under various conditions: without gel-immediately frozen (n = 30), with gel-immediately frozen, without gel-at room temperature (RT) for 5 h before freezing, with gel-at RT for 5 h before freezing, and additional sampling after 24 h without gel-immediate freezing. We found that sample collection with gel lubrication influenced specimen quality-half of the gel samples failing to meet processing limitation compared to those without gel. The effect of gel on testing quality dissipated after 24 h. However, when samples met post-sequencing filters, gel lubrication did not alter the microbial composition, individual taxa abundance or alpha and beta diversity. We recommend sampling either before gel exposure or 24 h after. These findings underscore the importance of considering sample collection methodologies in vaginal microbiome studies to ensure high-quality microbial data for accurate analysis.
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Géis , Microbiota , Manejo de Espécimes , Vagina , Feminino , Humanos , Vagina/microbiologia , Manejo de Espécimes/métodos , Gravidez , Adulto , Lubrificantes , RNA Ribossômico 16S/genética , Lubrificação , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Cremes, Espumas e Géis VaginaisRESUMO
OBJECTIVE: Excessive consumption of added sugars has been linked to the rise in obesity and associated metabolic abnormalities. Non-nutritive sweeteners (NNSs) offer a potential solution to reduce sugar intake, yet their metabolic safety remains debated. This study aimed to systematically assess the long-term metabolic effects of commonly used NNSs under both normal and obesogenic conditions. METHODS: To ensure consistent sweetness level and controlling for the acceptable daily intake (ADI), eight weeks old C57BL/6 male mice were administered with acesulfame K (ace K, 535.25 mg/L), aspartame (411.75 mg/L), sucralose (179.5 mg/L), saccharin (80 mg/L), or steviol glycoside (Reb M, 536.25 mg/L) in the drinking water, on the background of either regular or high-fat diets (in high fat diet 60% of calories from fat). Water or fructose-sweetened water (82.3.gr/L), were used as controls. Anthropometric and metabolic parameters, as well as microbiome composition, were analyzed following 20-weeks of exposure. RESULTS: Under a regular chow diet, chronic NNS consumption did not significantly affect body weight, fat mass, or glucose metabolism as compared to water consumption, with aspartame demonstrating decreased glucose tolerance. In diet-induced obesity, NNS exposure did not increase body weight or alter food intake. Exposure to sucralose and Reb M led to improved insulin sensitivity and decreased weight gain. Reb M specifically was associated with increased prevalence of colonic Lachnospiracea bacteria. CONCLUSIONS: Long-term consumption of commonly used NNSs does not induce adverse metabolic effects, with Reb M demonstrating a mild improvement in metabolic abnormalities. These findings provide valuable insights into the metabolic impact of different NNSs, aiding in the development of strategies to combat obesity and related metabolic disorders.
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Crohn disease (CD) burden has increased with globalization/urbanization, and the rapid rise is attributed to environmental changes rather than genetic drift. The Study Of Urban and Rural CD Evolution (SOURCE, n = 380) has considered diet-omics domains simultaneously to detect complex interactions and identify potential beneficial and pathogenic factors linked with rural-urban transition and CD. We characterize exposures, diet, ileal transcriptomics, metabolomics, and microbiome in newly diagnosed CD patients and controls in rural and urban China and Israel. We show that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirror those seen in CD. Ileal transcriptomics highlights personal metabolic and immune gene expression modules, that are directly linked to potential protective dietary exposures (coffee, manganese, vitamin D), fecal metabolites, and the microbiome. Bacteria-associated metabolites are primarily linked with host immune modules, whereas diet-linked metabolites are associated with host epithelial metabolic functions.
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Doença de Crohn , Dieta , Microbioma Gastrointestinal , População Rural , População Urbana , Doença de Crohn/microbiologia , Doença de Crohn/genética , Humanos , Masculino , Feminino , China/epidemiologia , Adulto , Israel/epidemiologia , Metabolômica , Estudos de Coortes , Pessoa de Meia-Idade , Fezes/microbiologia , Íleo/microbiologia , Íleo/metabolismo , Transcriptoma , Adulto JovemRESUMO
Spinal cord injury (SCI) is a devastating event that significantly changes daily function and quality of life and is linked to bowel and bladder dysfunction and frequent antibiotic treatment. We aimed to study the composition of the gut microbiome in individuals with SCI during the initial sub-acute rehabilitation process and during the chronic phase of the injury. This study included 100 fecal samples from 63 participants (Median age 40 years, 94% males): 13 cases with SCI in the sub-acute phase with 50 longitudinal samples, 18 cases with chronic SCI, and 32 age and gender-matched controls. We show, using complementary methods, that the time from the injury was a dominant factor linked with gut microbiome composition. Surprisingly, we demonstrated a lack of gut microbial recovery during rehabilitation during the sub-acute phase, with further deviation from the non-SCI control group in the chronic ambulatory SCI group. To generalize the results, we were able to show significant similarity of the signal when comparing to a previous cohort with SCI, to subjects from the American Gut Project who reported low physical activity, and to subjects from another population-based cohort who reported less normal stool consistency. Restoration of the microbiome composition may be another desirable measure for SCI recovery in the future, but further research is needed to test whether such restoration is associated with improved neurological outcomes and quality of life.
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Microbioma Gastrointestinal , Microbiota , Traumatismos da Medula Espinal , Masculino , Humanos , Adulto , Feminino , Qualidade de Vida , Exercício FísicoRESUMO
To evaluate the whiteout duration (WOd) and intensity (WOi) during Fiberoptic Endoscopic Evaluation of Swallowing (FEES) and examine their correlation with each other and age, gender, bolus consistencies, residue, and aspiration. Retrospective review of 75 videorecorded FEES. The first swallow of each of the following were scored: "Empty" swallow, semisolids, solids, and liquids (International dysphagia diet standardization initiative (IDDSI) 4, 7, 0, respectively). Data scored for each swallow included WOd, WOi, Penetration and aspiration scale (PAS), Pharyngeal residue (Yale Pharyngeal Residue Severity Rating Scale, YPR-SRS), and saliva pooling (Murray Secretion scale, MSS). The highest PAS and YPR-SRS for each consistency during the entire examination were also collected. WOd was significantly longer for stronger WOi in IDDSI4 swallows (p = 0.019). WOi was weaker for IDDSI0 swallows compared to IDDSI7, IDDSI4, and empty swallows (p < 0.05). Patients with saliva pooling had significantly shorter WOd (0.81 ± 0.3 s for MSS = 0 vs. 0.62 ± 0.24 for MSS = 3, p = 0.04). Lower WOi was associated with higher mean age for IDDSI0 (mean ages of 73 ± 12, 64 ± 14, 73 ± 7, 59 ± 16 years for intensity levels 1-4 respectively, p = 0.019). Swallows with weaker WOi and longer WOd had significantly more aspirations in IDDSI7 (28.8% of PAS ≥ 6 for intensity 2 vs 0% for intensity 4, p = 0.003 and 0.77 ± 0.4 s for PAS 1-2 vs. 1.02 ± 0.08 for PAS 6-8, p = 0.049). WOi and WOd are significantly associated with each other. WOi may vary for different bolus consistencies and decreases with age. Longer WOd and weaker WOi are associated with penetration-aspiration. Shorter WOd is associated with saliva pooling.
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OBJECTIVE: The association between follicular carcinoma and iodine deficiency (ID) is based on epidemiological studies and their inherent biases. The aim of the study was to assess the impact of long-term ID exposure on thyroid nodule cytology and final pathology in a distinct group of patients within a single institution. METHODS: Ethiopian origin patients were compared to an aged-matched group of non-Ethiopian patients. Demographics, risk factors, clinical presentation, cytology and pathology were collected and compared. Final outcomes were cytology and pathology distribution. RESULTS: A total of 489 (246 Ethiopian, 243 control) nodules of 461 patients (230 and 231 respectively) were included. Ethiopian patients had lower rates of thyroid cancer risk factors (p=0.05). Cytology analysis demonstrated significant group differences (p=0.03), as Ethiopian patients had higher rates of benign cytology (85% vs. 75.7%, respectively). Pathology analysis demonstrated a significantly lower malignancy rate among Ethiopian patients (39.2% (20/51) vs. 63.3% (31/49), p=0.027, respectively). The Ethiopian group had a significant higher rate of follicular carcinoma compared to the control group (25% [5/20] vs. 3.2% [1/31], p=0.034, respectively) and lower rates of papillary thyroid carcinoma (25% [5/20] vs. 61.3% [19/31], p=0.017, respectively). CONCLUSIONS: The association between ID and FC exists years following immigration and exposure to a better iodine diet, implying that differentiation may be affected in earlier stages and levels of exposure.
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Adenocarcinoma Folicular , Iodo , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Idoso , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/patologia , Estudos de Casos e Controles , Estudos Retrospectivos , Biópsia por Agulha Fina , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/etiologia , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/patologiaRESUMO
Ulcerative colitis (UC), Crohn's disease (CD), and celiac disease are prevalent intestinal inflammatory disorders with nonsatisfactory therapeutic interventions. Analyzing patient data-driven cohorts can highlight disease pathways and new targets for interventions. Long noncoding RNAs (lncRNAs) are attractive candidates, since they are readily targetable by RNA therapeutics, show relative cell-specific expression, and play key cellular functions. Uniformly analyzing gut mucosal transcriptomics from 696 subjects, we have highlighted lncRNA expression along the gastrointestinal (GI) tract, demonstrating that, in control samples, lncRNAs have a more location-specific expression in comparison with protein-coding genes. We defined dysregulation of lncRNAs in treatment-naive UC, CD, and celiac diseases using independent test and validation cohorts. Using the Predicting Response to Standardized Pediatric Colitis Therapy (PROTECT) inception UC cohort, we defined and prioritized lncRNA linked with UC severity and prospective outcomes, and we highlighted lncRNAs linked with gut microbes previously implicated in mucosal homeostasis. HNF1A-AS1 lncRNA was reduced in all 3 conditions and was further reduced in more severe UC form. Similarly, the reduction of HNF1A-AS1 ortholog in mice gut epithelia showed higher sensitivity to dextran sodium sulfate-induced colitis, which was coupled with alteration in the gut microbial community. These analyses highlight prioritized dysregulated lncRNAs that can guide future preclinical studies for testing them as potential targets.
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Doença Celíaca , Colite Ulcerativa , Doença de Crohn , RNA Longo não Codificante , Animais , Camundongos , Colite Ulcerativa/genética , Doença de Crohn/genética , RNA Longo não Codificante/genética , Doença Celíaca/genética , Transcriptoma , Estudos ProspectivosRESUMO
We aimed to determine microbial signature linked with lung cancer (LC) diagnosis and to define taxa linked with durable clinical benefit (DCB) of advanced LC patients. Stool samples for microbial 16S amplicon sequencing and clinical data were collected from 75 LC patients (50 of which were treated with checkpoint inhibitors) and 31 matched healthy volunteers. We compared LC to healthy controls and patients with DCB to those without. LC patients had lower α-diversity and higher between-subject diversity. Random Forests model to differentiate LC cases from controls ROC-AUC was 0.74. Clostridiales, Lachnospiraceae, and Faecalibacterium prausnitzii taxa abundance was decreased in LC compared to controls. High Akkermansia muciniphila correlated with DCB (HR 4.26, 95% CI 1.98-9.16), not only for the immunotherapy-treated patients. In addition, high Alistipes onderdonkii (HR 3.08, 95% CI 1.34-7.06) and high Ruminococcus (HR 7.76, 95% CI 3.23-18.65) correlated with DCB.Our results support the importance of gut microbiome in LC. We have validated the apparent predictive value of Akkermansia muciniphila, and highlighted Alistipes onderdonkii and Ruminococcus taxa correlation with DCB. Upon additional validations those can be used as biomarkers or as targets for future therapeutic interventions.
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Microbioma Gastrointestinal , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Bacteroidetes , Verrucomicrobia , ClostridialesRESUMO
BACKGROUND: Perturbagen analysis of Crohn's disease (CD) ileal gene expression data identified small molecules including eicosatetraynoic acid (ETYA), which may exert an antifibrotic effect. We developed a patient-specific human intestinal organoid (HIO) model system to test small molecule regulation of mitochondrial and wound-healing functions implicated in stricturing behavior. METHODS: HIOs were made from CD induced pluripotent stem cells with and without a loss-of-function haplotype in the DUOX2 gene implicated in ileal homeostasis and characterized under basal conditions and following exposure to butyrate and ETYA using RNA sequencing, flow cytometry, and immunofluorescent and polarized light microscopy. Mitochondrial activity was measured using high-resolution respirometry and tissue stiffness using atomic force microscopy. RESULTS: HIOs expressed core mitochondrial and extracellular matrix (ECM) genes and enriched biologic functions implicated in CD ileal strictures; ECM gene expression was suppressed by both butyrate and ETYA, with butyrate also suppressing genes regulating epithelial proliferation. Consistent with this, butyrate, but not ETYA, exerted a profound effect on HIO epithelial mitochondrial function, reactive oxygen species production, and cellular abundance. Butyrate and ETYA suppressed HIO expression of alpha smooth muscle actin expressed by myofibroblasts, type I collagen, and collagen protein abundance. HIOs exhibited tissue stiffness comparable to normal human ileum; this was reduced by chronic ETYA exposure in HIOs carrying the DUOX2 loss-of-function haplotype. CONCLUSIONS: ETYA regulates ECM genes implicated in strictures and suppresses collagen content and tissue stiffness in an HIO model. HIOs provide a platform to test personalized therapeutics, including small molecules prioritized by perturbagen analysis.
A subset of pediatric Crohn's disease patients develop intestinal strictures requiring surgery. The microbial metabolite butyrate and eicosatetraynoic acid regulate pathways implicated in stricture formation in a human intestinal organoid model system, which may be used to test new therapies.
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Doença de Crohn , Butiratos/metabolismo , Butiratos/farmacologia , Colágeno/metabolismo , Constrição Patológica/metabolismo , Doença de Crohn/genética , Oxidases Duais/metabolismo , Matriz Extracelular/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Mitocôndrias/metabolismo , Organoides/metabolismoRESUMO
BACKGROUND: Gut microbial alteration is implicated in inflammatory bowel disease but is noted in other diseases. Systematic comparison to define similarities and specificities is hampered since most studies focus on a single disease. RESULTS: We develop a pipeline to compare between disease cohorts starting from the raw V4 16S amplicon sequence variants. Including 12,838 subjects, from 59 disease cohorts, we demonstrate a predominant shared signature across diseases, indicating a common bacterial response to different diseases. We show that classifiers trained on one disease cohort predict relatively well other diseases due to this shared signal, and hence, caution should be taken when using such classifiers in real-world scenarios, where diseases are intermixed. Based on this common signature across a large array of diseases, we develop a universal dysbiosis index that successfully differentiates between cases and controls across various diseases and can be used for prioritizing fecal donors and samples with lower disease probability. Finally, we identify a set of IBD-specific bacteria, which can direct mechanistic studies and design of IBD-specific microbial interventions. CONCLUSIONS: A robust non-specific general response of the gut microbiome is detected in a large array of diseases. Disease classifiers may confuse between different diseases due to this shared microbial response. Our universal dysbiosis index can be used as a tool to prioritize fecal samples and donors. Finally, the IBD-specific taxa may indicate a more direct association to gut inflammation and disease pathogenesis, and those can be further used as biomarkers and as future targets for interventions.
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Colite Ulcerativa , Doença de Crohn , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Bactérias/genética , Colite Ulcerativa/microbiologia , Doença de Crohn/microbiologia , Disbiose/microbiologia , Fezes/microbiologia , Humanos , Doenças Inflamatórias Intestinais/microbiologiaRESUMO
The human gut microbiome develops during the first years of life, followed by a relatively stable adult microbiome. Day care attendance is a drastic change that exposes children to a large group of peers in a diverse environment for prolonged periods, at this critical time of microbial development, and therefore has the potential to affect microbial composition. We characterize the effect of day care on the gut microbial development throughout a single school year in 61 children from 4 different day care facilities, and in additional 24 age-matched home care children (n = 268 samples, median age of entering the study was 12 months). We show that day care attendance is a significant and impactful factor in shaping the microbial composition of the growing child, the specific daycare facility and class influence the gut microbiome, and each child becomes more similar to others in their day care. Furthermore, in comparison to home care children, day care children have a different gut microbial composition, with enrichment of taxa more frequently observed in older populations. Our results provide evidence that daycare may be an external factor that contributes to gut microbiome maturation and make-up in early childhood.
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Microbioma Gastrointestinal , Microbiota , Adulto , Idoso , Criança , Pré-Escolar , Hospital Dia , Humanos , LactenteRESUMO
The coronavirus disease 2019 (COVID-19) has rapidly spread around the world, impacting the lives of many individuals. Growing evidence suggests that the nasopharyngeal and respiratory tract microbiome are influenced by various health and disease conditions, including the presence and the severity of different viral disease. To evaluate the potential interactions between Severe Acute Respiratory Syndrome Corona 2 (SARS-CoV-2) and the nasopharyngeal microbiome. Microbial composition of nasopharyngeal swab samples submitted to the clinical microbiology lab for suspected SARS-CoV-2 infections was assessed using 16S amplicon sequencing. The study included a total of 55 nasopharyngeal samples from 33 subjects, with longitudinal sampling available for 12 out of the 33 subjects. 21 of the 33 subjects had at least one positive COVID-19 PCR results as determined by the clinical microbiology lab. Inter-personal variation was the strongest factor explaining > 75% of the microbial variation, irrespective of the SARS-CoV-2 status. No significant effect of SARS-CoV-2 on the nasopharyngeal microbial community was observed using multiple analysis methods. These results indicate that unlike some other viruses, for which an effect on the microbial composition was noted, SARS-CoV-2 does not have a strong effect on the nasopharynx microbial habitants.
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COVID-19/microbiologia , Microbiota , Nasofaringe/microbiologia , SARS-CoV-2/fisiologia , Adulto , Idoso , COVID-19/virologia , Feminino , Humanos , Masculino , Microbiota/genética , Pessoa de Meia-Idade , RNA Ribossômico 16S/genéticaRESUMO
INTRODUCTION: Rehabilitating hearing loss is highly important due to its positive impact on the ability to understand speech, and the related consequences on family, social and work communication abilities. Children with hearing loss have learning difficulties that adversely affect speech and language acquirement. Most patients with hearing loss can use conventional hearing aids that are partially or completely placed in the external ear canal. Middle ear implants are used when conventional hearing aids are not suitable due to medical reasons, mainly diseases of the external ear canal and the tympanic membrane. The external component of the middle ear implant digitally translates the acoustic information (sound waves) to the implanted part, where the digital information is back-translated to mechanical information (vibrations) which vibrates the ossicle to which it is attached. We present a patient who underwent a Vibrant Soundbridge implantation after unsuccessfully using hearing aids due to recurrent otitis externa. The patient's hearing improved significantly. We conclude that middle ear implants can be an effective treatment for patients who cannot use conventional hearing aids.
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Auxiliares de Audição , Perda Auditiva Neurossensorial , Perda Auditiva , Prótese Ossicular , Otite Externa , Criança , Feminino , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/terapia , HumanosRESUMO
BACKGROUND & AIMS: Environmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED. METHODS: The Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan. Biomarkers were measured at 9 months and tested for association with growth at 24 months. The duodenal methylome and transcriptome were determined in 52 undernourished SEEM participants and 42 North American controls and patients with celiac disease. RESULTS: After accounting for growth at study entry, circulating insulin-like growth factor-1 (IGF-1) and ferritin predicted linear growth, whereas leptin correlated with future weight gain. The EED transcriptome exhibited suppression of antioxidant, detoxification, and lipid metabolism genes, and induction of anti-microbial response, interferon, and lymphocyte activation genes. Relative to celiac disease, suppression of antioxidant and detoxification genes and induction of antimicrobial response genes were EED-specific. At the epigenetic level, EED showed hyper-methylation of epithelial metabolism and barrier function genes, and hypo-methylation of immune response and cell proliferation genes. Duodenal coexpression modules showed association between lymphocyte proliferation and epithelial metabolic genes and histologic severity, fecal energy loss, and wasting (weight-for-length/height Z < -2.0). Leptin was associated with expression of epithelial carbohydrate metabolism and stem cell renewal genes. Immune response genes were attenuated by giardia colonization. CONCLUSIONS: Children with reduced circulating IGF-1 are more likely to experience stunting. Leptin and a gene signature for lymphocyte activation and dysregulated lipid metabolism are implicated in wasting, suggesting new approaches for EED refractory to nutritional intervention. ClinicalTrials.gov, Number: NCT03588013. (https://clinicaltrials.gov/ct2/show/NCT03588013).
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Enteropatias/genética , Mucosa Intestinal/imunologia , Metabolismo dos Lipídeos/genética , Ativação Linfocitária/genética , Desnutrição/complicações , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Doença Celíaca/genética , Doença Celíaca/patologia , Doença Celíaca/fisiopatologia , Proliferação de Células/genética , Desenvolvimento Infantil , Pré-Escolar , Creatinina/urina , Metilação de DNA , Epigenoma , Feminino , Ferritinas/sangue , Genômica , Transtornos do Crescimento/etiologia , Humanos , Lactente , Recém-Nascido , Fator de Crescimento Insulin-Like I/metabolismo , Enteropatias/complicações , Enteropatias/patologia , Enteropatias/fisiopatologia , Leptina/sangue , Linfócitos/fisiologia , Masculino , Estresse Oxidativo/genética , Paquistão , TranscriptomaRESUMO
In nature, bacteria form biofilms-differentiated multicellular communities attached to surfaces. Within these generally sessile biofilms, a subset of cells continues to express motility genes. We found that this subpopulation enabled Bacillus subtilis biofilms to expand on high-friction surfaces. The extracellular matrix (ECM) protein TasA was required for the expression of flagellar genes. In addition to its structural role as an adhesive fiber for cell attachment, TasA acted as a developmental signal stimulating a subset of biofilm cells to revert to a motile phenotype. Transcriptomic analysis revealed that TasA stimulated the expression of a specific subset of genes whose products promote motility and repress ECM production. Spontaneous suppressor mutations that restored motility in the absence of TasA revealed that activation of the biofilm-motility switch by the two-component system CssR/CssS antagonized the TasA-mediated reversion to motility in biofilm cells. Our results suggest that although mostly sessile, biofilms retain a degree of motility by actively maintaining a motile subpopulation.
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Bacillus subtilis/fisiologia , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Proteínas da Matriz Extracelular/metabolismoRESUMO
High fructose consumption is one of the hallmarks of Western diets and has been found to induce MeS symptoms in parallel to gut microbial dysbiosis. However, the causality between those two is still elusive. Here, we studied whether a significant modification of gut microbial composition by antibiotics can influence the fructose-induced metabolic changes. Male Sprague-Dawley (SD) rats were divided into four groups including controls, controls + antibiotics, high fructose diet (HFrD, 60% fructose), HFrD + antibiotics (n = 7-8 in each group) for a period of 8-weeks. The high fructose diet increased blood pressure (BP), triglyceride (TG), fatty liver and the expression of hepatic genes related to lipogenesis, and fructose transport and metabolism. In addition, fructose changed the microbial composition and increased acetic and butyric acids in fecal samples but not in the blood. Antibiotic treatment significantly reduced microbial diversity and modified the microbial composition in the samples. However, minimal or no effect was seen in the metabolic phenotypes. In conclusion, high fructose consumption (60%) induced metabolic changes and dysbiosis in rats. However, antibiotic treatment did not reverse the metabolic phenotype. Therefore, the metabolic changes are probably independent of a specific microbiome profile.
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Antibacterianos/farmacologia , Dieta/efeitos adversos , Disbiose , Frutose/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Fígado/efeitos dos fármacos , Masculino , Síndrome Metabólica , Ratos , Ratos Sprague-DawleyRESUMO
The relation between pharyngeal tonsil and the bony nasopharynx determines the nasopharyngeal airway patency. Despite its importance, an anatomical study utilizing advanced imaging has not been conducted. The aim of the study was to evaluate the pharyngeal tonsil and bony nasopharynx depth and their ratio (adenoid-nasopharyngeal ratio [ANR]) with relation to sex and age in the general pediatric population. After excluding reported history of adenoidectomy, acute upper airway illness, allergy, and poor quality, 200 randomly selected head computed tomographies (CTs) of children were evaluated. CTs were divided into five age groups (0-5, 5.1-8, 8.1-11, 11.1-14, and 14.1-17 years). For each CT scan, the pharyngeal tonsil, bony nasopharynx and ANR values were calculated. A significant difference was found in the bony nasopharynx and pharyngeal tonsil depth between the five age subgroups (P < 0.001). Both bony nasopharynx and pharyngeal tonsil depth significantly increased between the age groups of 0-5 years to 5.1-8 years (4.17 mm increase, P < 0.001 and 3.47 mm increase, P < 0.009, respectively). The pharyngeal tonsil depth gradually decreases following the age of 8 years. No difference was found between age groups beyond age of eight for both the pharyngeal tonsil tissue and the bony nasopharynx. The ANR has an upward trend in the age group of 5.1-8 years. No sexual predilection was found. The bony nasopharynx and the pharyngeal tonsil tissue both grow during childhood. Different growth rates result in the narrowest airway in the age group of 5.1-8 years (ANR peak). These growth curves should be taken under consideration when treating pediatric pharyngeal tonsil hypertrophy. Clin. Anat., 33:1019-1024, 2020. © 2019 Wiley Periodicals, Inc.
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Tonsila Faríngea/diagnóstico por imagem , Tonsila Faríngea/crescimento & desenvolvimento , Nasofaringe/diagnóstico por imagem , Nasofaringe/crescimento & desenvolvimento , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores SexuaisRESUMO
A major challenge in understanding gene regulation is the unequivocal identification of enhancer elements and uncovering their connections to genes. We present GeneHancer, a novel database of human enhancers and their inferred target genes, in the framework of GeneCards. First, we integrated a total of 434 000 reported enhancers from four different genome-wide databases: the Encyclopedia of DNA Elements (ENCODE), the Ensembl regulatory build, the functional annotation of the mammalian genome (FANTOM) project and the VISTA Enhancer Browser. Employing an integration algorithm that aims to remove redundancy, GeneHancer portrays 285 000 integrated candidate enhancers (covering 12.4% of the genome), 94 000 of which are derived from more than one source, and each assigned an annotation-derived confidence score. GeneHancer subsequently links enhancers to genes, using: tissue co-expression correlation between genes and enhancer RNAs, as well as enhancer-targeted transcription factor genes; expression quantitative trait loci for variants within enhancers; and capture Hi-C, a promoter-specific genome conformation assay. The individual scores based on each of these four methods, along with geneenhancer genomic distances, form the basis for GeneHancer's combinatorial likelihood-based scores for enhancergene pairing. Finally, we define 'elite' enhancergene relations reflecting both a high-likelihood enhancer definition and a strong enhancergene association. GeneHancer predictions are fully integrated in the widely used GeneCards Suite, whereby candidate enhancers and their annotations are displayed on every relevant GeneCard. This assists in the mapping of non-coding variants to enhancers, and via the linked genes, forms a basis for variantphenotype interpretation of whole-genome sequences in health and disease. Database URL: http://www.genecards.org/.