Objective
Dysbiosis of the infant gut microbiota may have long‐term health consequences. This study aimed to determine the impact of maternal intrapartum antibiotic prophylaxis (IAP) on infant gut ...microbiota, and to explore whether breastfeeding modifies these effects.
Design
Prospective pregnancy cohort of Canadian infants born in 2010–2012: the Canadian Healthy Infant Longitudinal Development (CHILD) Study.
Setting
General community.
Sample
Representative sub‐sample of 198 healthy term infants from the CHILD Study.
Methods
Maternal IAP exposures and birth method were documented from hospital records and breastfeeding was reported by mothers. Infant gut microbiota was characterised by Illumina 16S rRNA sequencing of faecal samples at 3 and 12 months.
Main outcome measures
Infant gut microbiota profiles.
Results
In this cohort, 21% of mothers received IAP for Group B Streptococcus prophylaxis or pre‐labour rupture of membranes; another 23% received IAP for elective or emergency caesarean section (CS). Infant gut microbiota community structures at 3 months differed significantly with all IAP exposures, and differences persisted to 12 months for infants delivered by emergency CS. Taxon‐specific composition also differed, with the genera Bacteroides and Parabacteroides under‐represented, and Enterococcus and Clostridium over‐represented at 3 months following maternal IAP. Microbiota differences were especially evident following IAP with emergency CS, with some changes (increased Clostridiales and decreased Bacteroidaceae) persisting to 12 months, particularly among non‐breastfed infants.
Conclusions
Intrapartum antibiotics in caesarean and vaginal delivery are associated with infant gut microbiota dysbiosis, and breastfeeding modifies some of these effects. Further research is warranted to explore the health consequences of these associations.
Tweetable
Maternal #antibiotics during childbirth alter the infant gut #microbiome.
Tweetable
Maternal #antibiotics during childbirth alter the infant gut #microbiome.
We report the first measurement of coherent elastic neutrino-nucleus scattering (CEvNS) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two ...independent analyses prefer CEvNS over the background-only null hypothesis with greater than 3σ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2±0.7)×10^{-39} cm^{2}-consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the CEvNS process and provides improved constraints on nonstandard neutrino interactions.
Purpose
Demographic change will lead to an increase in age-associated cancers. The demand for primary treatment, especially oncologic therapies, is difficult to predict. This work is an attempt to ...project the demand for radiation therapy (RT) in 2030, taking into account demographic changes using prostate cancer (PC) as an example.
Materials and methods
Using the GENESIS database of the Federal Statistical Office, we retrieved demographic population projections for 2030 and retrospective demographic surveys from 1999 to 2019. Additionally, we queried incidence rates for PC in the respective age groups of 50–54, 55–59, 60–64, 65–69, 70–74, 75–79, 80–84, and +85 years from 1999–2019 via the Federal Cancer Registry of the Robert Koch Institute. We used a regression method to determine the age-dependent correlation between the incidence of PC and the population size of the respective age group by combining the data from 1999 to 2019. This information was used to calculate the incidence rates in the age groups of the expected population for 2030 and the expected new cases of PC in 2030. Finally, we extrapolated the indications for the demand for RT based on data from the Report on Cancer Incidence in Germany from 2016.
Results
Considering a population-dependent incidence rate, an increase in new cases of PC is expected. This increase is particularly evident in the age groups of 70–74 and 80–84 years. With regards to RT, the estimate indicates an overall increase of 27.4% in demand. There is also a shift in RT demands towards older patients, especially in the 80- to 84-year-old age group.
Conclusion
We observe an age-associated increase in primary cases of PC. This is likely to result in an increased demand for RT. The exact demand cannot be predicted. However, trends can be estimated to plan for the demand. This, though, requires a good database from cancer registries.
Summary
Background
The gut microbiota is established during infancy and plays a fundamental role in shaping host immunity. Colonization patterns may influence the development of atopic disease, but ...existing evidence is limited and conflicting.
Objective
To explore associations of infant gut microbiota and food sensitization.
Methods
Food sensitization at 1 year was determined by skin prick testing in 166 infants from the population‐based Canadian Healthy Infant Longitudinal Development (CHILD) study. Faecal samples were collected at 3 and 12 months, and microbiota was characterized by Illumina 16S rRNA sequencing.
Results
Twelve infants (7.2%) were sensitized to ≥ 1 common food allergen at 1 year. Enterobacteriaceae were overrepresented and Bacteroidaceae were underrepresented in the gut microbiota of food‐sensitized infants at 3 months and 1 year, whereas lower microbiota richness was evident only at 3 months. Each quartile increase in richness at 3 months was associated with a 55% reduction in risk for food sensitization by 1 year (adjusted odds ratio 0.45, 95% confidence interval 0.23–0.87). Independently, each quartile increase in Enterobacteriaceae/Bacteroidaceae ratio was associated with a twofold increase in risk (2.02, 1.07–3.80). These associations were upheld in a sensitivity analysis among infants who were vaginally delivered, exclusively breastfed and unexposed to antibiotics. At 1 year, the Enterobacteriaceae/Bacteroidaceae ratio remained elevated among sensitized infants, who also tended to have decreased abundance of Ruminococcaceae.
Conclusions and Clinical Relevance
Low gut microbiota richness and an elevated Enterobacteriaceae/Bacteroidaceae ratio in early infancy are associated with subsequent food sensitization, suggesting that early gut colonization may contribute to the development of atopic disease, including food allergy.
White Americans who participate in the Black Lives Matter movement, men who attended the Women’s March, and people from the Global North who work to reduce poverty in the Global South—advantaged ...group members (sometimes referred to as allies) often engage in action for disadvantaged groups. Tensions can arise, however, over the inclusion of advantaged group members in these movements, which we argue can partly be explained by their motivations to participate. We propose that advantaged group members can be motivated to participate in these movements (a) to improve the status of the disadvantaged group, (b) on the condition that the status of their own group is maintained, (c) to meet their own personal needs, and (d) because this behavior aligns with their moral beliefs. We identify potential antecedents and behavioral outcomes associated with these motivations before describing the theoretical contribution our article makes to the psychological literature.
Two once‐daily rivaroxaban dosing regimens were compared with warfarin for stroke prevention in patients with non‐valvular atrial fibrillation in ROCKET AF: 20 mg for patients with normal/mildly ...impaired renal function and 15 mg for patients with moderate renal impairment. Rivaroxaban population pharmacokinetic (PK)/pharmacodynamic (PD) modeling data from ROCKET AF patients (n = 161) are reported and are used to confirm established rivaroxaban PK and PK/PD models and to re‐estimate values of the models' parameters for the current AF population. An oral one‐compartment model with first‐order absorption adequately described rivaroxaban PK. Age, renal function, and lean body mass influenced the PK model. Prothrombin time and prothrombinase‐induced clotting time exhibited a near‐linear relationship with rivaroxaban plasma concentration; inhibitory effects were observed through to 24 hours post‐dose. Rivaroxaban plasma concentration and factor Xa activity had an inhibitory maximum‐effect (Emax) relationship. Renal function (on prothrombin time; prothrombinase‐induced clotting time) and age (on factor Xa activity) had moderate effects on PK/PD models. PK and PK/PD models were shown to be adequate for describing the current dataset. These findings confirm the modeling and empirical results that led to the selection of doses tested against warfarin in ROCKET AF.
Uterine leiomyomata (UL) are the most common neoplasms of the female reproductive tract and primary cause for hysterectomy, leading to considerable morbidity and high economic burden. Here we conduct ...a GWAS meta-analysis in 35,474 cases and 267,505 female controls of European ancestry, identifying eight novel genome-wide significant (P < 5 × 10
) loci, in addition to confirming 21 previously reported loci, including multiple independent signals at 10 loci. Phenotypic stratification of UL by heavy menstrual bleeding in 3409 cases and 199,171 female controls reveals genome-wide significant associations at three of the 29 UL loci: 5p15.33 (TERT), 5q35.2 (FGFR4) and 11q22.3 (ATM). Four loci identified in the meta-analysis are also associated with endometriosis risk; an epidemiological meta-analysis across 402,868 women suggests at least a doubling of risk for UL diagnosis among those with a history of endometriosis. These findings increase our understanding of genetic contribution and biology underlying UL development, and suggest overlapping genetic origins with endometriosis.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder that affects carriers, principally males, of premutation alleles (55–200 CGG repeats) of the fragile X ...mental retardation 1 (FMR1) gene. Clinical features of FXTAS include progressive intention tremor and gait ataxia, accompanied by characteristic white matter abnormalities on MRI. The neuropathological hallmark of FXTAS is an intranuclear inclusion, present in both neurons and astrocytes throughout the CNS. Prior to the current work, the nature of the associations between inclusion loads and molecular measures (e.g. CGG repeat) was not defined. Post-mortem brain and spinal cord tissue has been examined for gross and microscopic pathology in a series of 11 FXTAS cases (males, age 67–87 years at the time of death). Quantitative counts of inclusion numbers were performed in various brain regions in both neurons and astrocytes. Inclusion counts were compared with specific molecular (CGG repeat, FMR1 mRNA level) and clinical (age of onset, age of death) parameters. In the current series, the three most prominent neuropathological characteristics are (i) significant cerebral and cerebellar white matter disease, (ii) associated astrocytic pathology with dramatically enlarged inclusion-bearing astrocytes prominent in cerebral white matter and (iii) the presence of intranuclear inclusions in both brain and spinal cord. The pattern of white matter pathology is distinct from that associated with hypertensive vascular disease and other diseases of white matter. Spongiosis was present in the middle cerebellar peduncles in seven of the eight cases in which those tissues were available for study. There is inclusion formation in cranial nerve nucleus XII and in autonomic neurons of the spinal cord. The most striking finding is the highly significant association between the number of CGG repeats and the numbers of intranuclear inclusions in both neurons and astrocytes, indicating that the CGG repeat is a powerful predictor of neurological involvement in males, both clinically (age of death) and neuropathologically (number of inclusions).
It has been proposed that CD4 T-cell responses to Staphylococcus aureus (SA) can inadvertently enhance neoplastic progression in models of skin cancer and cutaneous T-cell lymphoma (CTCL). In this ...prospective study, we explored the effect of transient antibiotic treatment on tumor cells and disease activity in 8 patients with advanced-stage CTCL. All patients experienced significant decrease in clinical symptoms in response to aggressive, transient antibiotic treatment. In some patients, clinical improvements lasted for more than 8 months. In 6 of 8 patients, a malignant T-cell clone could be identified in lesional skin, and a significant decrease in the fraction of malignant T cells was observed following antibiotics but an otherwise unchanged treatment regimen. Immunohistochemistry, global messenger RNA expression, and cell-signaling pathway analysis indicated that transient aggressive antibiotic therapy was associated with decreased expression of interleukin-2 high-affinity receptors (CD25), STAT3 signaling, and cell proliferation in lesional skin. In conclusion, this study provides novel evidence suggesting that aggressive antibiotic treatment inhibits malignant T cells in lesional skin. Thus, we provide a novel rationale for treatment of SA in advanced CTCL.
•Antibiotic treatment of CTCL inhibits disease activity and lymphocyte proliferation in lesional skin.•We provide a novel rationale for aggressive antibiotic treatment as an important adjuvant therapy in patients with advanced stage CTCL.
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