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1.
Headache ; 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39129307

RESUMEN

OBJECTIVE: To identify distinct clinical or imaging subtypes of spontaneous intracranial hypotension (SIH) due to spinal cerebrospinal fluid (CSF) venous fistula (CVF). BACKGROUND: Spontaneous intracranial hypotension is classically understood to present clinically with an orthostatic headache and stereotyped brain magnetic resonance imaging (MRI) findings; however, most prior literature examining clinical and brain MRI features of SIH has focused on all types of spinal CSF leaks concurrently. This study aimed to evaluate whether data support the possibility of internally consistent subtypes based on brain imaging features and clinical symptoms analogous to those seen in primary headache syndromes. METHODS: This retrospective cross-sectional single-institution study included 48 consecutive patients meeting the International Classification of Headache Disorders, 3rd edition criteria for SIH due to CVF. Clinical symptoms, pre-treatment brain MRI, and symptom duration were analyzed. Clinical and MRI data were analyzed to identify patterns and associations between symptoms and imaging findings. RESULTS: A total of 20 males and 28 females were evaluated, with a mean (standard deviation) age of 61 (10) years. In all, 44/48 (92%) patients experienced headaches, though 18/48 (40%) did not endorse relief when flat, including six of the 48 (13%) with worsening symptoms when flat. In all, 19/48 (40%) patients reported at least one migraine symptom, and six of the 48 (13%) presented with at least one migraine symptom and had no relief when flat. Clinical symptoms clustered primarily into a "classic" presentation consisting of relief when flat, occipital head pain, comorbid neck pain, a pressure/throbbing headache quality, and an "atypical" presentation that was characterized by having several differences: less relief when flat (nine of 22 (41%) vs. 20/23 (87.0%), p = 0.002; odds ratio [OR] 0.110, 95% confidence interval [CI] 0.016-0.53), more frontal head pain (14/22 (64%) vs. one of 23 (4%), p < 0.001; OR 35.0, 95% CI 4.2-1681.0), less neck pain (two of 21 (4.5%) vs. nine of 13 (69.6%), p < 0.001; OR 0.023, 95% CI 0.0005-0.196), and more stabbing/sharp headache quality (nine of 22 (41%) vs. two of 23 (9%), p = 0.017; OR 7.0, 95% CI 1.18-75.9). Brain MRI findings clustered into three groups: those presenting with most imaging findings of SIH concurrently, those with brain sag but less pachymeningeal/venous engorgement, and those with pachymeningeal/venous engorgement but less brain sag. CONCLUSION: This study highlights the clinical and imaging diversity among patients with SIH due to CVF, challenging the reliance on classic orthostatic headache alone for diagnosis. The findings suggest the existence of distinct SIH subtypes based on clinical and imaging presentations, underscoring the need for comprehensive evaluation in patients with suspected CVF. Future research should further elucidate the relationship between clinical symptoms and imaging findings, aiming to refine diagnostic criteria and enhance understanding of SIH's pathophysiology.

2.
medRxiv ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38978655

RESUMEN

Postsurgical falls have significant patient and societal implications but remain challenging to identify and track. Detecting postsurgical falls is crucial to improve patient care for older adults and reduce healthcare costs. Large language models (LLMs) offer a promising solution for reliable and automated fall detection using unstructured data in clinical notes. We tested several LLM prompting approaches to postsurgical fall detection in two different healthcare systems with three open-source LLMs. The Mixtral-8×7B zero-shot had the best performance at Stanford Health Care (PPV = 0.81, recall = 0.67) and the Veterans Health Administration (PPV = 0.93, recall = 0.94). These results demonstrate that LLMs can detect falls with little to no guidance and lay groundwork for applications of LLMs in fall prediction and prevention across many different settings.

3.
J Dev Behav Pediatr ; 45(3): e195-e202, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38896565

RESUMEN

OBJECTIVE: Monolingual Spanish speakers-many of whom identify as Hispanic/Latine-often experience barriers to accessing psychology services, including language access. Integrated primary care (IPC) clinics, where individuals receive psychological services within primary care, aim to improve service accessibility. However, minoritized populations are less likely to engage with these services than non-Hispanic/Latine White individuals. Few studies examine psychology treatment engagement within pediatric integrated clinics for Spanish-speaking families. This study investigated differences in psychology treatment engagement for Spanish-speaking families and the role of patient-provider language concordance within pediatric IPC. METHODS: A retrospective chart review examined data from a multiethnic sample of 887 patients (M age = 8.97 yrs, 55.69% male, 64.83% Hispanic/Latine, 6.99% non-Hispanic/Latine White, 41.71% Spanish-preferring) from an urban pediatric IPC clinic serving a high proportion of Hispanic/Latine, Spanish-speaking families. We examined the association between language preference and patient-provider language concordance on service engagement using hierarchical linear regression. RESULTS: Spanish-preferring families were more likely than English-preferring families to engage in psychology services. Working with a Spanish-speaking provider during an initial psychology visit was unrelated to psychology treatment engagement for Spanish-preferring families. CONCLUSION: Higher engagement for Spanish-preferring families seems to reflect the clinic's reputation as a center for linguistically accessible services. While linguistic accessibility remains important, our study did not detect an effect of language concordance during the initial psychology visit and subsequent treatment engagement. The findings highlight the importance of providing culturally responsive and linguistically accessible mental health services for Spanish-speaking families.


Asunto(s)
Hispánicos o Latinos , Multilingüismo , Humanos , Masculino , Hispánicos o Latinos/estadística & datos numéricos , Femenino , Niño , Estudios Retrospectivos , Atención Primaria de Salud/estadística & datos numéricos , Servicios de Salud Mental/estadística & datos numéricos , Prestación Integrada de Atención de Salud , Aceptación de la Atención de Salud/etnología , Aceptación de la Atención de Salud/estadística & datos numéricos , Accesibilidad a los Servicios de Salud , Barreras de Comunicación , Lenguaje , Trastornos Mentales/terapia , Trastornos Mentales/etnología
4.
Neurol Clin Pract ; 14(3): e200290, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38699599

RESUMEN

Purpose of Review: This review focuses on the challenges of diagnosing and treating spontaneous intracranial hypotension (SIH), a condition caused by spinal CSF leakage. It emphasizes the need for increased awareness and advocates for early and thoughtful use of empirical epidural blood patches (EBPs) in suspected cases. Recent Findings: SIH diagnosis is hindered by variable symptoms and inconsistent imaging results, including normal brain MRI and unreliable spinal opening pressures. It is crucial to consider SIH in differential diagnoses, especially in patients with connective tissue disorders. Early EBP intervention is shown to improve outcomes. Summary: SIH remains underdiagnosed and undertreated, requiring heightened awareness and understanding. This review promotes proactive EBP use in managing suspected SIH and calls for continued research to advance diagnostic and treatment methods, emphasizing the need for innovative imaging techniques for accurate diagnosis and timely intervention.

5.
PLoS Comput Biol ; 20(5): e1011869, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38739671

RESUMEN

We introduce an innovative, data-driven topological data analysis (TDA) technique for estimating the state spaces of dynamically changing functional human brain networks at rest. Our method utilizes the Wasserstein distance to measure topological differences, enabling the clustering of brain networks into distinct topological states. This technique outperforms the commonly used k-means clustering in identifying brain network state spaces by effectively incorporating the temporal dynamics of the data without the need for explicit model specification. We further investigate the genetic underpinnings of these topological features using a twin study design, examining the heritability of such state changes. Our findings suggest that the topology of brain networks, particularly in their dynamic state changes, may hold significant hidden genetic information.


Asunto(s)
Encéfalo , Red Nerviosa , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Algoritmos , Encéfalo/fisiología , Mapeo Encefálico/métodos , Análisis por Conglomerados , Biología Computacional/métodos , Imagen por Resonancia Magnética/métodos , Modelos Neurológicos , Red Nerviosa/fisiología
6.
J Eat Disord ; 12(1): 63, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773635

RESUMEN

BACKGROUND: Weight gain and nutritional rehabilitation are essential first steps to achieve medical stabilization in anorexia nervosa, and frequent resistance to weight gain requires patients to consume high kilocalorie loads. Adaptive hypometabolism is common when patients begin treatment, and rebound hypermetabolism is suspected to be a significant barrier to weight gain. The aim of this review was to summarize existing data describing metabolic changes in anorexia nervosa during weight restoration. The reported findings challenge current hypotheses of weight gain resistance and highlight key areas for future research. METHODS: Using scoping review guidelines, three databases were searched for studies investigating metabolic changes in anorexia nervosa before and after renourishment. Two reviewers systematically screened the titles and abstracts of 447 articles, and full-text versions of 106 studies were assessed for eligibility. A total of 36 studies were included for review. Data regarding the study description, sample population (including age, weight, BMI, duration of treatment, and caloric intake), and metabolic variable descriptions were extracted. RESULTS: Female patients with anorexia nervosa from studies across 13 countries were included. Across the studies, average BMI increased from 13.7 kg/m2 at admission to 17.57 kg/m2. Patients presented to treatment with clinically reduced energy expenditure levels. After varying levels of nutritional rehabilitation and weight restoration, measured energy expenditure increased significantly in 76% of the studies. Energy expenditure values at the second timepoint increased to the standard range for normal weight female teenagers and adults. Despite these increases, the studies do not indicate the presence of a hypermetabolic state during renourishment. Additionally, all studies including both measured and predicted energy expenditure reported that predicted energy expenditure overestimated measured values. CONCLUSION: This study provides a detailed evaluation of the literature investigating energy expenditure and metabolic rate in patients with anorexia nervosa before and following a period of renourishment. The findings from this review identify important gaps in the current beliefs of energy expenditure in anorexia nervosa and highlight a need for further exploration of metabolic alterations during weight restoration.


Nutritional rehabilitation and weight restoration are two primary goals of anorexia nervosa treatment that pose significant physiological and psychological challenges for patients. Patients often require high caloric loads to continue an adequate weight gain trajectory, but the underlying cause of weight gain resistance remains unknown. We completed a scoping review of research into energy expenditure and metabolic rate during treatment. Our search identified 447 relevant articles from academic databases, and 106 were deemed eligible after screening. We extracted data, including sample characteristics, kilocalorie intake, energy expenditure, and treatment information, from 36 studies. When individuals arrived for treatment, their energy expenditure was lower than that of individuals without an eating disorder due to the prolonged state of nutrient deprivation. After varying amounts of time and kilocalorie intake, most studies reported significant increases in energy expenditure. However, energy expenditure after a period of renourishment did not indicate an overactive metabolism (i.e., "hypermetabolism"). Funders should consider supporting exploration of additional factors that may be functioning as barriers to weight gain during treatment, in pursuit of making treatment more efficient and long-lasting. Additionally, future research describing metabolism in anorexia nervosa should provide more consistent methodologies, robust statical testing, and comprehensive reporting of dietary intake.

7.
Neurology ; 102(12): e209449, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38820488

RESUMEN

BACKGROUND AND OBJECTIVES: Spinal CSF leaks lead to spontaneous intracranial hypotension (SIH). While International Classification of Headache Disorders, Third Edition (ICHD-3) criteria necessitate imaging confirmation or low opening pressure (OP) for SIH diagnosis, their sensitivity may be limited. We offered epidural blood patches (EBPs) to patients with symptoms suggestive of SIH, with and without a documented low OP or confirmed leak on imaging. This study evaluates the efficacy of this strategy. METHODS: We conducted a prospective cohort study with a nested case-control design including all patients who presented to a tertiary headache clinic with clinical symptoms of SIH who completed study measures both before and after receiving an EBP between August 2016 and November 2018. RESULTS: The mean duration of symptoms was 8.7 ± 8.1 years. Of 85 patients assessed, 69 did not meet ICHD-3 criteria for SIH. At an average of 521 days after the initial EBP, this ICHD-3-negative subgroup experienced significant improvements in Patient-Reported Outcomes Measurement Information System (PROMIS) Global Physical Health score of +3.3 (95% CI 1.5-5.1), PROMIS Global Mental Health score of +1.8 (95% CI 0.0-3.5), Headache Impact Test (HIT)-6 head pain score of -3.8 (95% CI -5.7 to -1.8), Neck Disability Index of -4.8 (95% CI -9.0 to -0.6) and PROMIS Fatigue of -2.3 (95% CI -4.1 to -0.6). Fifty-four percent of ICHD-3-negative patients achieved clinically meaningful improvements in PROMIS Global Physical Health and 45% in HIT-6 scores. Pain relief following lying flat prior to treatment was strongly associated with sustained clinically meaningful improvement in global physical health at an average of 521 days (odds ratio 1.39, 95% CI 1.1-1.79; p < 0.003). ICHD-3-positive patients showed high rates of response and previously unreported, treatable levels of fatigue and cognitive deficits. DISCUSSION: Patients who did not conform to the ICHD-3 criteria for SIH showed moderate rates of sustained, clinically meaningful improvements in global physical health, global mental health, neck pain, fatigue, and head pain after EBP therapy. Pre-treatment improvement in head pain when flat was associated with later, sustained improvement after EBP therapy among patients who did not meet the ICHD-3 criteria. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that epidural blood patch is an effective treatment of suspected CSF leak not conforming to ICHD-3 criteria for SIH.


Asunto(s)
Parche de Sangre Epidural , Pérdida de Líquido Cefalorraquídeo , Hipotensión Intracraneal , Humanos , Femenino , Masculino , Parche de Sangre Epidural/métodos , Persona de Mediana Edad , Adulto , Pérdida de Líquido Cefalorraquídeo/terapia , Hipotensión Intracraneal/terapia , Estudios Prospectivos , Estudios de Casos y Controles , Resultado del Tratamiento , Estudios de Cohortes , Medición de Resultados Informados por el Paciente
8.
Neurol Clin Pract ; 14(2): e200272, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38585435

RESUMEN

Background and Objectives: Spontaneous intracranial hypotension (SIH) caused by a spinal CSF leak is a multisymptom syndrome, which can dramatically affect physical and mental health. However, systematic data on health-related quality of life (HRQoL) and mental health are scarce. We hypothesized that surgical treatment leads to significant and sustained improvements in HRQoL and mental health in patients with SIH. Methods: In this single-center cohort study, we prospectively collected HRQoL and mental health data in patients undergoing surgical closure of a spinal CSF leak from September 2020 to November 2022. EuroQoL (EQ-5D-5L), including the health state index (EQ-Index) and the visual analog scale (EQ-VAS), measured HRQoL. The 21-item version of the Depression Anxiety Stress Scales (DASS-21) measured symptoms of mental health. Follow-ups were performed 3 and 6 months postoperatively. Primary outcome was the change in EQ-Index, EQ-VAS, and DASS-21 subscales. Secondary outcome was the impact of baseline depression symptoms on HRQoL outcomes following surgery. Results: Seventy-four patients were included. EQ-VAS improved from 40 (interquartile range [IQR] 30-60) preoperatively to 70 (IQR 55-85) at 3 months and to 72 (IQR 60-88) at 6 months postoperatively (p < 0.001, respectively). EQ-Index increased from 0.683 (IQR 0.374-0.799) to 0.877 (0.740-0.943) at 3 months and to 0.907 (0.780-0.956) at 6 months postoperatively (p < 0.001, respectively). Depression, anxiety, and stress significantly improved after surgery. Preoperative depressive symptoms did not affect the HRQoL outcome. Discussion: The severe impact of a spinal CSF leak on HRQoL and mental health significantly improved after closure of the leak. Higher levels of depressive symptoms do not predict worse outcomes and should not discourage invasive treatment. Further systematic evaluation of outcomes, with special regard to quality of life, is needed, as it allows a comparison of symptom burden between SIH and more familiar diseases as well as a comparison of different treatment modalities in future studies.

9.
Res Sq ; 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38586018

RESUMEN

Background/Objectives: Metabolic and bariatric surgery (MBS) is the most effective treatment for severe obesity; however, a significant subset of patients does not achieve expected weight loss or have substantial weight recurrence over time. The intestinal energy harvest is a potential determinant of varying weight loss outcomes, but with limited exploration. We assess the relationships between diet, intestinal energy harvest, and weight outcomes over 24 months in individuals who have undergone MBS. Subjects/Methods: Calorie absorption was assessed with bomb calorimetry and dietary questionnaires before and after MBS. Within a total of 67 patients, fecal energy density was measured in 67, 56, 60, 67, 44, 47 samples at 0, 1, 6, 12, 18, and 24 months, respectively. Multivariate regression was developed to identify potential weight loss predictors, and random forest algorithms were employed to forecast weight results based on intestinal energy harvest. Results: Intestinal energy harvest enhanced the predictability of patient weight loss outcomes with random forest models. A notable difference in relative fecal energy content was observed between patients experiencing optimal and sub-optimal weight loss (p<0.01). Prior to MBS, an increased energy content in feces (indicating less energy absorption) is associated with greater weight loss after the operation. Associations between diet and energy harvest were insignificant. Conclusion: MBS changes energy harvest capacity post-surgery. A higher relative fecal energy content (lower energy absorption) at one month correlates with better weight loss outcomes at 6M, 12M, 18M and 24M post-MBS. Findings may guide the development of diagnostic tools and treatment guidelines for patients at risk of suboptimal weight loss outcomes. CLINICAL TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03065426).

10.
Headache ; 64(4): 460-463, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38613228

RESUMEN

Spontaneous intracranial hypotension (SIH) commonly results from ventral spinal cerebrospinal fluid (CSF) leaks and epidural patches are advocated as first-line treatment. Complications such as superficial siderosis can arise but have previously been reported only in the context of long-term persistent, ongoing, CSF leak and SIH. We report a case of a patient with SIH from a ventral spinal CSF leak that was treated with epidural patching and experienced complete resolution of SIH. Four years later SIH symptoms recurred, and brain magnetic resonance imaging unexpectedly showed the interval accumulation of hemosiderin pigmentation on the cerebellum and brainstem during the period when the patient was without symptoms of SIH. This case uniquely demonstrates the progression of superficial siderosis despite the apparent resolution of SIH. Our findings suggest two divergent pathophysiological outcomes from spinal ventral dural tear: (1) CSF loss causing SIH; and (2) persistent low-level bleeding arising from the spinal dural tear leading to superficial siderosis. These divergent pathophysiologies had a discordant response to epidural patching. Epidural patching successfully treated the SIH but did not prevent the progression of superficial siderosis, indicating that some patients may require more than epidural patching despite symptom resolution. This case highlights the need for post-treatment monitoring protocols in patients with ventral spinal CSF leaks and SIH and raises important questions about the adequacy of epidural patching in certain SIH cases arising from ventral spinal CSF leak.


Asunto(s)
Parche de Sangre Epidural , Hipotensión Intracraneal , Adulto , Humanos , Masculino , Pérdida de Líquido Cefalorraquídeo/complicaciones , Pérdida de Líquido Cefalorraquídeo/terapia , Pérdida de Líquido Cefalorraquídeo/etiología , Progresión de la Enfermedad , Hipotensión Intracraneal/terapia , Hipotensión Intracraneal/complicaciones , Hipotensión Intracraneal/etiología , Hipotensión Intracraneal/diagnóstico por imagen , Imagen por Resonancia Magnética , Siderosis/complicaciones
11.
School Psych Rev ; 53(1): 1-16, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38487040

RESUMEN

Many racial-ethnic minoritized individuals are repeatedly exposed to subtle actions reflecting racial slights, termed racial microaggressions (RMAs), which are associated with adjustment problems in early adult and adult populations. Early adolescence represents a unique developmental period when minoritized youth begin their racial-ethnic identity exploration and are subjected to stereotypes and prejudice, thereby making them vulnerable to RMAs. Based upon the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist, a systematic literature search, screening and review of RMA literature focusing on high schoolers and younger youth was conducted and yielded 54 publications. This paper reviewed the publications and identified gaps in the field such as the need for systematic research on early adolescents including the frequency and severity of RMAs and the important contributions of peers, parents and teachers for RMA victims, and the need for more evidence-based programming for middle schoolers. Findings suggest that developing school-based microaggression anti-racism programs is clearly needed for minoritized and White youth.

12.
Physiol Rep ; 12(6): e15982, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38514894

RESUMEN

Hypertension (HTN) is common among athletes and the most recent epidemiologic data reports that cardiovascular (CV) sudden death is significantly greater in African Americans (AAs). Gut microbial dysbiosis (a poorly diverse stool microbial profile) has been associated with HTN in sedentary people but microbial characteristics of athletes with HTN are unknown. Our purpose was to differentiate microbiome characteristics associated with BP status in AA collegiate athletes. Thirty AA collegiate athletes were stratified by normal BP (systolic BP (SBP) ≤130 mmHg; n = 15) and HTN (SBP ≥130 mmHg; n = 15). 16S rRNA gene sequencing was performed on stool samples to identify microbes at the genus level. We did not observe any significant differences in alpha diversity, but beta diversity was different between groups. Principal coordinate analysis was significantly different (PERMANOVA, p < 0.05, R = 0.235) between groups. Spearman rank correlations showed a significant (p < 0.05) correlation between systolic BP and abundances for Adlercreutzia (R = 0.64), Coprococcus (R = 0.49), Granulicatella (R = 0.63), and Veillonella (R = 0.41). Gut microbial characteristics were associated with differentially abundant microbial genus' and BP status. These results will direct future studies to define the functions of these microbes associated with BP in athletes.


Asunto(s)
Microbioma Gastrointestinal , Hipertensión , Humanos , Presión Sanguínea/fisiología , Microbioma Gastrointestinal/fisiología , Proyectos Piloto , Negro o Afroamericano , ARN Ribosómico 16S/genética , Atletas
13.
Reg Anesth Pain Med ; 49(4): 293-297, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38388018

RESUMEN

BACKGROUND: Postdural puncture headache has been traditionally viewed as benign, self-limited, and highly responsive to epidural blood patching (EBP) when needed. A growing body of data from patients experiencing unintended dural puncture (UDP) in the setting of attempted labor epidural placement suggests a minority of patients will have more severe and persistent symptoms. However, the mechanisms accounting for the failure of EBP following dural puncture remain obscure. An understanding of these potential mechanisms is critical to guide management decisions in the face of severe and persistent cerebrospinal fluid (CSF) leak. CASE PRESENTATION: We report the case of a peripartum patient who developed a severe and persistent CSF leak unresponsive to multiple EBPs following a UDP during epidural catheter placement for labor analgesia. Lumbar MRI revealed a ventral rather than dorsal epidural fluid collection suggesting that the needle had crossed the thecal sac and punctured the ventral dura, creating a puncture site not readily accessible to blood injected in the dorsal epidural space. The location of this persistent ventral dural defect was confirmed with digital subtraction myelography, permitting a transdural surgical exploration and repair of the ventral dura with resolution of the severe intracranial hypotension. CONCLUSIONS: A ventral rather than dorsal dural puncture is one mechanism that may contribute to both severe and persistent spinal CSF leak with resulting intracranial hypotension following a UDP.


Asunto(s)
Hipotensión Intracraneal , Cefalea Pospunción de la Duramadre , Humanos , Hipotensión Intracraneal/diagnóstico por imagen , Hipotensión Intracraneal/etiología , Parche de Sangre Epidural/métodos , Pérdida de Líquido Cefalorraquídeo/diagnóstico por imagen , Pérdida de Líquido Cefalorraquídeo/etiología , Pérdida de Líquido Cefalorraquídeo/terapia , Punciones/efectos adversos , Cefalea Pospunción de la Duramadre/diagnóstico , Cefalea Pospunción de la Duramadre/etiología , Cefalea Pospunción de la Duramadre/terapia , Enfermedad Iatrogénica , Uridina Difosfato
15.
bioRxiv ; 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38328247

RESUMEN

Undernutrition in children commonly disrupts the structure and function of the small intestinal microbial community, leading to enteropathies, compromised metabolic health, and impaired growth and development. The mechanisms by which diet and microbes mediate the balance between commensal and pathogenic intestinal flora remain elusive. In a murine model of undernutrition, we investigated the direct interactions Giardia lamblia, a prevalent small intestinal pathogen, on indigenous microbiota and specifically on Lactobacillus strains known for their mucosal and growth homeostatic properties. Our research reveals that Giardia colonization shifts the balance of lactic acid bacteria, causing a relative decrease in Lactobacillus spp . and an increase in Bifidobacterium spp . This alteration corresponds with a decrease in multiple indicators of mucosal and nutritional homeostasis. Additionally, protein-deficient conditions coupled with Giardia infection exacerbate the rise of primary bile acids and susceptibility to bile acid-induced intestinal barrier damage. In epithelial cell monolayers, Lactobacillus spp . mitigated bile acid-induced permeability, showing strain-dependent protective effects. In vivo, L. plantarum, either alone or within a Lactobacillus spp consortium, facilitated growth in protein-deficient mice, an effect attenuated by Giardia , despite not inhibiting Lactobacillus colonization. These results highlight Giardia's potential role as a disruptor of probiotic functional activity, underscoring the imperative for further research into the complex interactions between parasites and bacteria under conditions of nutritional deficiency.

16.
Microbiome ; 11(1): 277, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38124090

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in vitro definition fully predicts mucosal colonization in vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis. RESULTS: Germ-free inflammation-susceptible interleukin-10-deficient (Il10-/-) and inflammation-resistant WT mice were colonized with a consortium of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10-/- mice. These E. coli expand in Il10-/- mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization. CONCLUSIONS: Our findings establish the in vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in vivo colonization dynamics of patient-derived bacteria in murine models. Video Abstract.


Asunto(s)
Infecciones por Escherichia coli , Microbioma Gastrointestinal , Animales , Humanos , Ratones , Adulto Joven , Disbiosis/complicaciones , Escherichia coli/genética , Infecciones por Escherichia coli/microbiología , Inflamación/metabolismo , Interleucina-10 , Mucosa Intestinal/microbiología , ARN Ribosómico 16S/genética , ARN Ribosómico 16S/metabolismo
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