Intestinal microbiome landscaping : insight in community assemblage and implications for microbial modulation strategies

High individuality, large complexity and limited understanding of the mechanisms underlying human intestinal microbiome function remain the major challenges for designing beneficial modulation strategies. Exemplified by the analysis of intestinal bacteria in a thousand Western adults, we discuss key concepts of the human intestinal microbiome landscape, i.e. the compositional and functional 'core', the presence of community types and the existence of alternative stable states. Genomic investigation of core taxa revealed functional redundancy, which is expected to stabilize the ecosystem, as well as taxa with specialized functions that have the potential to shape the microbiome landscape. The contrast between Prevotella-and Bacteroides-dominated systems has been well described. However, less known is the effect of not so abundant bacteria, for example, Dialister spp. that have been proposed to exhibit distinct bistable dynamics. Studies employing time-series analysis have highlighted the dynamical variation in the microbiome landscape with and without the effect of defined perturbations, such as the use of antibiotics or dietary changes. We incorporate ecosystem-level observations of the human intestinal microbiota and its keystone species to suggest avenues for designing microbiome modulation strategies to improve host health.Peer reviewe

Feasibility of Metatranscriptome Analysis from Infant Gut Microbiota: Adaptation to Solid Foods Results in Increased Activity of Firmicutes at Six Months

Peer reviewe

Clinical and Physiological Correlates of Irritability in Depression: Results from the Netherlands Study of Depression and Anxiety

Objective. Irritable and nonirritable depressed patients differ on demographic and clinical characteristics. We investigated whether this extends to psychological and physiological measures. Method. We compared irritable and nonirritable unipolar depressed patients on symptomatology, personality, and (psycho)physiological measures (cortisol, cholesterol, and heart rate variability). Symptomatology was reassessed after one year, and we also compared depressed patients who were irritable or non-irritable at both time points (Irr++ versus Irr−−). Results. Almost half (46%; N = 420) of the sample was classified as irritable. These patients scored higher on depression severity, anxiety, hypomanic symptoms, and psychological variables. No differences were observed on physiological markers after correction for depression severity. The same pattern was found when comparing Irr++ and Irr−− groups. Conclusion. Irritable and non-irritable depressed patients differ on clinical and psychological variables, but not on the currently investigated physiological markers. The clinical relevance of the distinction and the significance of the hypomanic symptoms remain to be demonstrated

Feasibility of Metatranscriptome Analysis from Infant Gut Microbiota: Adaptation to Solid Foods Results in Increased Activity of Firmicutes at Six Months

Newborns are rapidly colonized by microbes and their intestinal tracts contain highly dynamic and rapidly developing microbial communities in the first months of life. In this study, we describe the feasibility of isolating mRNA from rapidly processed faecal samples and applying deep RNA-Seq analysis to provide insight into the active contributors of the microbial community in early life. Specific attention is given to the impact of removing rRNA from the mRNA on the phylogenetic and transcriptional profiling and its analysis depth. A breastfed baby was followed in the first six months of life during adaptation to solid food, dairy products, and formula. It was found that, in the weaning period, the total transcriptional activity of Actinobacteria, mainly represented by Bifidobacterium, decreased while that of Firmicutes increased over time. Moreover, Firmicutes and Actinobacteria, including the canonical Bifidobacteria as well as Collinsella, were found to be important contributors to carbohydrate fermentation and vitamin biosynthesis in the infant intestine. Finally, the expression of Lactobacillus rhamnosus-like genes was detected, likely following transfer from the mother who consumed L. rhamnosus GG. The study indicates that metatranscriptome analysis of the infant gut microbiota is feasible on infant stool samples and can be used to provide insight into the core activities of the developing community.</p

A novel technique capable of taking 'protected' biopsies for reliable assessment of the distribution of microbiota along the colonic mucosa

We evaluated a novel 'protected' biopsy method to reliably ascertain the spatial distribution of the mucosa-adherent colonic microbiota. Apart from minor differences at genus level, overall similarities along the colon were high between the various areas, irrespective of protected or unprotected sampling.Peer reviewe

Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target

Heat shock proteins (HSP) are highly conserved across eukaryotic and prokaryotic species. These proteins play a role in response to cellular stressors, protecting cells from damage and facilitating recovery. In tumor cells, HSPs can have cytoprotective effects and interfere with apoptotic cascades. This study was performed to assess the prognostic and predictive values of the gene expression of HSP family members in canine osteosarcoma (OS) and their potential for targeted therapy. Gene expressions for HSP were assessed using quantitative PCR (qPCR) on 58 snap-frozen primary canine OS tumors and related to clinic-pathological parameters. A significant increased expression of HSP60 was found in relation to shorter overall survival and an osteoblastic phenotype. Therefore, the function of HSP60 was investigated in more detail. Immunohistochemical analysis revealed heterogeneous staining for HSP60 in tumors. The highest immunoreactivity was found in tumors of short surviving dogs. Next HSP expression was shown in a variety of canine and human OS cell lines by qPCR and Western blot. In two highly metastatic cell lines HSP60 expression was silenced using siRNA resulting in decreased cell proliferation and induction of apoptosis in both cell lines. It is concluded that overexpression of HSP60 is associated with a poor prognosis of OS and should be evaluated as a new target for therapy

Clinical characteristics and diagnoses of 1213 children referred to a first seizure clinic

Objective: New-onset seizure-like events (SLEs) are common in children, but differentiating between epilepsy and its mimics is challenging. This study provides an overview of the clinical characteristics, diagnoses, and corresponding etiologies of children evaluated at a first seizure clinic (FSC), which will be helpful for all physicians involved in the care of children with SLEs. Methods: We included 1213 children who were referred to the FSC of a Dutch tertiary children's hospital over a 13-year period and described their clinical characteristics, first routine EEG recording results, and the distribution and specification of their eventual epilepsy and non-epilepsy diagnoses. The time interval to correct diagnosis and the diagnostic accuracy of the FSC were evaluated. Results: “Epilepsy” was eventually diagnosed in 407 children (33.5%), “no epilepsy” in 737 (60.8%), and the diagnosis remained “unclear” in 69 (5.7%). Epileptiform abnormalities were seen in 60.9% of the EEG recordings in the “epilepsy” group, and in 5.7% and 11.6% of the “no epilepsy” and “unclear” group, respectively. Of all children with final “epilepsy” and “no epilepsy” diagnoses, 68.6% already received their diagnosis at FSC consultation, and 2.9% of the children were initially misdiagnosed. The mean time to final diagnosis was 2.0 months, and 91.3% of all children received their final diagnosis within 12 months after the FSC consultation. Significance: We describe the largest pediatric FSC cohort to date, which can serve as a clinical frame of reference. The experience and expertise built at FSCs will improve and accelerate diagnosis in children with SLEs. Plain language summary: Many children experience events that resemble but not necessarily are seizures. Distinguishing between seizures and seizure mimics is important but challenging. Specialized first-seizure clinics can help with this. Here, we report data from 1213 children who were referred to the first seizure clinic of a Dutch children's hospital. One-third of them were diagnosed with epilepsy. In 68.8% of all children—with and without epilepsy—the diagnosis was made during the first consultation. Less than 3% were misdiagnosed. This study may help physicians in what to expect regarding the diagnoses in children who present with events that resemble seizures

Normal hip strength and range of motion values in youth and adult female national football teams: Data from 504 assessments

Objectives: To determine normal hip adduction- and abduction strength and range of motion (ROM) values for youth and adult female national team football players, and evaluate if increasing age, playing position and leg dominance were associated with these strength and ROM values. Design: Cohort study. Setting: National football center. Participants: 344 unique asymptomatic female football players. Main outcome measures: Hip internal/external rotation (°), Bent Knee Fall Out test (cm), hip adduction/abduction strength(N) and ratio, and normalised hip adduction/abduction torque (Nm/kg). Results: A total of 504 assessments were performed. A total of 107 players underwent two (n = 67), three (n = 27) or four (n = 13) assessments. Mean peak hip adduction strength was 39% greater in 20 + Y old players 170 (±53 N) than in 13Y old players 122 (±28 N). Normalised hip adduction torque was 9% greater: 2.5 (±0.8Nm/kg) versus 2.3 (±0.5Nm/kg). A positive association between age and all strength measurements was found, while a negative association between age and hip external rotation and total hip rotation was found. No clinically relevant differences were found for the associations between playing position, leg dominance and hip strength- and ROM values. Conclusion: Normal values for hip strength and range of motion in youth and adult female national football players are presented that can be used as clinical reference values

Dental implants in dentate primary and secondary Sjögren's syndrome patients:A multicenter prospective cohort study

Objectives: To prospectively assess the clinical performance and patient-reported outcomes of dental implants in dentate patients with primary and secondary Sjögren's syndrome (pSS and sSS, respectively) compared to patients without SS. Materials and Methods: Thirty-seven implants were placed in 17 patients with pSS/sSS and 26 implants in 17 non-SS patients to replace missing (pre)molars. Clinical performance, marginal bone-level changes, patient satisfaction, and oral health-related quality of life (OHRQoL) were assessed at 1 (T1), 6 (T6), 12 (T12), and 18 (T18) months after placement of the superstructure. Marginal bone-level changes were measured on standardized dental radiographs. Clinical parameters included implant and crown survival, plaque, bleeding and gingival indices, and probing depth. Patient satisfaction and OHRQoL were assessed with validated questionnaires. Results: Implant survival at T18 was 100% in the patients with pSS/sSS and 96.2% in the non-SS group. Mean marginal bone loss at T18 did not differ between patients with pSS/sSS and non-SS patients, 1.10 ± 1.04 and 1.04 ± 0.75 mm, respectively (p =.87). Clinical performance was good with no differences between the groups for all outcome measures (p >.05). OHRQoL in patients with pSS/sSS had improved significantly after placement of implant supported crowns at all measuring moments compared to baseline (p <.05). Nevertheless, patient satisfaction and OHRQoL remained significantly higher for patients without SS at all measuring moments (p <.05). Conclusion: Dental implants can be successfully applied in dentate patients with pSS/sSS and have a positive effect on OHRQoL

Prehospital Management of Traumatic Brain Injury across Europe: A CENTER-TBI Study.

BACKGROUND: Prehospital care for traumatic brain injury (TBI) is important to prevent secondary brain injury. We aim to compare prehospital care systems within Europe and investigate the association of system characteristics with the stability of patients at hospital arrival. METHODS: We studied TBI patients who were transported to CENTER-TBI centers, a pan-European, prospective TBI cohort study, by emergency medical services between 2014 and 2017. The association of demographic factors, injury severity, situational factors, and interventions associated with on-scene time was assessed using linear regression. We used mixed effects models to investigate the case mix adjusted variation between countries in prehospital times and interventions. The case mix adjusted impact of on-scene time and interventions on hypoxia (oxygen saturation <90%) and hypotension (systolic blood pressure <100mmHg) at hospital arrival was analyzed with logistic regression. RESULTS: Among 3878 patients, the greatest driver of longer on-scene time was intubation (+8.3 min, 95% CI: 5.6-11.1). Secondary referral was associated with shorter on-scene time (-5.0 min 95% CI: -6.2- -3.8). Between countries, there was a large variation in response (range: 12-25 min), on-scene (range: 16-36 min) and travel time (range: 15-32 min) and in prehospital interventions. These variations were not explained by patient factors such as conscious level or severity of injury (expected OR between countries: 1.8 for intubation, 1.8 for IV fluids, 2.0 for helicopter). On-scene time was not associated with the regional EMS policy (p= 0.58). Hypotension and/or hypoxia were seen in 180 (6%) and 97 (3%) patients in the overall cohort and in 13% and 7% of patients with severe TBI (GCS <8). The largest association with secondary insults at hospital arrival was with major extracranial injury: the OR was 3.6 (95% CI: 2.6-5.0) for hypotension and 4.4 (95% CI: 2.9-6.7) for hypoxia. DISCUSSION: Hypoxia and hypotension continue to occur in patients who suffer a TBI, and remain relatively common in severe TBI. Substantial variation in prehospital care exists for patients after TBI in Europe, which is only partially explained by patient factors