Early life determinants of the oral microbiota have not been thoroughly elucidated. We studied the association of birth and early childhood characteristics with oral microbiota composition using 16 S ribosomal RNA (rRNA) gene sequencing in a population-based Swedish cohort of 59 children sampled at 6, 12 and 24 months of age. Repeated-measurement regression models adjusted for potential confounders confirmed and expanded previous knowledge about the profound shift of oral microbiota composition in early life. These alterations included increased alpha diversity, decreased beta diversity and alteration of bacterial composition with changes in relative abundance of 14 of the 20 most common operational taxonomic units (OTUs). We also found that birth characteristics, breastfeeding and antibiotic use were associated with overall phyla distribution and/or with the relative abundance of specific OTUs. Further, we detected a novel link between morning salivary cortisol level, a physiological marker of neuroendocrine activity and stress, and overall phyla distribution as well as with decreased abundance of the most common OTU mapped to the Streptococcaceae family. In conclusion, a major part of the maturation of the oral microbiome occurs during the first two years of life, and this development may be influenced by early life circumstances.
Background The case-fatality rate of severe leptospirosis can exceed 50%. While prompt supportive care can improve survival, predicting those at risk of developing severe disease is challenging, particularly in settings with limited diagnostic support. Methodology/Principal findings We retrospectively identified all adults with laboratory-confirmed leptospirosis in Far North Queensland, Australia, between January 1998 and May 2016. Clinical, laboratory and radiological findings at presentation were correlated with the patients’ subsequent clinical course. Medical records were available in 402 patients; 50 (12%) had severe disease. The presence of oliguria (urine output ≤500 mL/24 hours, odds ratio (OR): 16.4, 95% confidence interval (CI): 6.9–38.8, p<0.001), abnormal auscultatory findings on respiratory examination (OR 11.2 (95% CI: 4.7–26.5, p<0.001) and hypotension (systolic blood pressure ≤100 mmHg, OR 4.3 (95% CI 1.7–10.7, p = 0.002) at presentation independently predicted severe disease. A three-point score (the SPiRO score) was devised using these three clinical variables, with one point awarded for each. A score could be calculated in 392 (98%) patients; the likelihood of severe disease rose incrementally: 8/287 (3%), 14/70 (20%), 18/26 (69%) and 9/9 (100%) for a score of 0, 1, 2 and 3 respectively (p = 0.0001). A SPiRO score <1 had a negative predictive value for severe disease of 97% (95% CI: 95–99%). Conclusions/Significance A simple, three-point clinical score can help clinicians rapidly identify patients at risk of developing severe leptospirosis, prompting early transfer to referral centres for advanced supportive care. This inexpensive, bedside assessment requires minimal training and may have significant utility in the resource-limited settings which bear the greatest burden of disease.
BackgroundSevere leptospirosis can have a case-fatality rate of over 50%, even with intensive care unit (ICU) support. Multiple strategies–including protective ventilation and early renal replacement therapy (RRT)–have been recommended to improve outcomes. However, management guidelines vary widely around the world and there is no consensus on the optimal approach.Methodology/Principal findingsAll cases of leptospirosis admitted to the ICU of Cairns Hospital in tropical Australia between 1998 and 2018 were retrospectively reviewed. The patients’ demographics, presentation, management and clinical course were examined. The 55 patients’ median (interquartile range (IQR)) age was 47 (32–62) years and their median (IQR) APACHE III score was 67 (48–105). All 55 received appropriate antibiotic therapy, 45 (82%) within the first 6 hours. Acute kidney injury was present in 48/55 (87%), 18/55 (33%) required RRT, although this was usually not administered until traditional criteria for initiation were met. Moderate to severe acute respiratory distress syndrome developed in 37/55 (67%), 32/55 (58%) had pulmonary haemorrhage, and mechanical ventilation was required in 27/55 (49%). Vasopressor support was necessary in 34/55 (62%). Corticosteroids were prescribed in 20/55 (36%). The median (IQR) fluid balance in the initial three days of ICU care was +1493 (175–3567) ml. Only 2/55 (4%) died, both were elderly men with multiple comorbidities.ConclusionIn patients with severe leptospirosis in tropical Australia, prompt ICU support that includes early antibiotics, protective ventilation strategies, conservative fluid resuscitation, traditional thresholds for RRT initiation and corticosteroid therapy is associated with a very low case-fatality rate. Prospective studies are required to establish the relative contributions of each of these interventions to optimal patient outcomes.
Our results suggest that severe psychological stress in early life may be associated with premature development of certain malignancies, particularly cancers related to smoking and HPV infection.
We conclude that adolescent stress resilience, plausibly by influencing behavioural choices and social patterns, constitutes an important determinant of adult cancer occurrence. Increased awareness of long-term consequences in susceptible individuals may help direct future efforts to reduce cancer burden in adults.
Although development of microbiota in childhood has been linked to chronic immune-related conditions, early childhood determinants of microbiota development have not been fully elucidated. We used 16S rRNA sequencing to analyse faecal and saliva samples from 83 children at four time-points during their first 2 years of life and from their mothers. Our findings confirm that gut microbiota in infants have low diversity and highlight that some properties are shared with the oral microbiota, although inter-individual differences are present. A considerable convergence in gut microbiota composition was noted across the first 2 years of life, towards a more diverse adult-like microbiota. Mode of delivery accounted for some of the inter-individual variation in early childhood, but with a pronounced attenuation over time. Our study extends previous research with further characterization of the major shift in gut microbiota composition during the first 2 years of life.
Background:Adverse childhood experiences (ACEs) have consistently been associated with elevated risk of multiple adverse health outcomes, yet their contribution to coping ability and psychiatric resilience in adulthood is unclear.Methods:Cross-sectional data were derived from the ongoing Stress-And-Gene-Analysis cohort, representing 30% of the Icelandic nationwide female population, 18–69 years. Participants in the current study were 26,198 women with data on 13 ACEs measured with the ACE-International Questionnaire. Self-reported coping ability was measured with the Connor-Davidson Resilience Scale and psychiatric resilience was operationalized as absence of psychiatric morbidity. Generalized linear regression assuming normal or Poisson distribution were used to assess the associations of ACEs with coping ability and psychiatric resilience controlling for multiple confounders.Results:Number of ACEs was inversely associated with adult resilience in a dose-dependent manner; every 1SD unit increase in ACE scores was associated with both lower levels of coping ability (β = −0.14; 95% CI-0.15,–0.13) and lower psychiatric resilience (β = −0.28; 95% CI-0.29,–0.27) in adulthood. Compared to women with 0 ACEs, women with ≥5 ACEs had 36% lower prevalence of high coping ability (PR = 0.64, 95% CI 0.59,0.70) and 58% lower prevalence of high psychiatric resilience (PR = 0.42; 95% CI 0.39,0.45). Specific ACEs including emotional neglect, bullying, sexual abuse and mental illness of household member were consistently associated with reduced adult resilience. We observed only slightly attenuated associations after controlling for adult socioeconomic factors and social support in adulthood.Conclusions:Cumulative ACE exposure is associated with lower adult resilience among women, independent of adult socioeconomic factors and social support, indicating that adult resilience may be largely determined in childhood.Funding:This work was supported by the European Research Council (Consolidator grant; UAV, grant number 726413), and the Icelandic Center for Research (Grant of excellence; UAV, grant number 163362-051). HBD was supported by a doctoral grant from the University of Iceland Research Fund.
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