Impact of Antibiotic Treatment on the Gut Microbiome and its Resistome in Hematopoietic Stem Cell Transplant Recipients.

Antibiotic-resistant bacterial infections are increasingly an issue in allogenic hematopoietic stem cell transplant patients. How antibiotic treatment impacts antibiotic resistance in the human gut microbiome remains poorly understood in vivo. Here, a total of 577 fecal samples from 233 heavily antibiotic-treated transplant patients were examined using high-resolution prescription data and shotgun metagenomics. The 13 most frequently used antibiotics were significantly associated with 154 (40% of tested associations) microbiome features. Use of broad-spectrum ß-lactam antibiotics was most markedly associated with microbial disruption and increase in resistome features. The enterococcal vanA gene was positively associated with 8 of the 13 antibiotics, and in particular piperacillin/tazobactam and vancomycin. Here, we highlight the need for a high-resolution approach in understanding the development of antibiotic resistance in the gut microbiome. Our findings can be used to inform antibiotic stewardship and combat the increasing threat of antibiotic resistance.

Metabolic Potential of the Gut Microbiome Is Significantly Impacted by Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Allogeneic hematopoietic stem cell transplantation (aHSCT) is a putative curative treatment for malignant hematologic disorders. During transplantation, the immune system is suppressed/eradicated through a conditioning regimen (non-myeloablative or myeloablative) and replaced with a donor immune system. In our previous study, we showed changes in gut taxonomic profiles and a decrease in bacterial diversity post-transplant. In this study, we expand the cohort with 114 patients and focus on the impact of the conditioning regimens on taxonomic features and the metabolic functions of the gut bacteria. This is, to our knowledge, the first study to examine the metabolic potential of the gut microbiome in this patient group. Adult aHSCT recipients with shotgun sequenced stool samples collected day -30 to +28 relative to aHSCT were included. One sample was selected per patient per period: pre-aHSCT (day -30-0) and post-aHSCT (day 1-28). In total, 254 patients and 365 samples were included. Species richness, alpha diversity, gene richness and metabolic richness were all lower post-aHSCT than pre-aHSCT and the decline was more pronounced for the myeloablative group. The myeloablative group showed a decline in 36 genera and an increase in 15 genera. For the non-myeloablative group, 30 genera decreased and 16 increased with lower fold changes than observed in the myeloablative group. For the myeloablative group, 32 bacterial metabolic functions decreased, and one function increased. For the non-myeloablative group, three functions decreased, and two functions increased. Hence, the changes in taxonomy post-aHSCT caused a profound decline in bacterial metabolic functions especially in the myeloablative group, thus providing new evidence for associations of myeloablative conditioning and gut dysbiosis from a functional perspective.

A field study investigating sensory manifestations in recreational female cyclists using a novel female-specific cycling pad.

This randomised controlled field study aimed to design a female-specific cycling pad with reduced padding in the crotch area (half-pad) and test its effects on self-reported sensory manifestations in comparison with full-padded cycling bib shorts. Recreational female road cyclists (n = 183) participated (divided into two groups). Self-reported sensory manifestations were collected six times over 12 weeks. Sitting discomfort, wetness perception, thermal, texture sensation, and wear discomfort decreased over time for the crotch and sitting-bones areas in both groups. Irritation and tenderness in the crotch area also decreased over time in both groups. Irritation and tenderness in the sitting-bones area were only higher at week two in the half-pad compared with the full-pad group. Cycling with the half-padded shorts compared with the full-padded ones had no negative effects on sensory manifestations beside the observed transient change at week two. This suggests that foam thickness in the crotch area can be reduced in female-specific cycling pads. Practitioner's Summary: Road cycling might result in discomfort and non-traumatic injuries in the female genital area. This field study compares two different cycling pads; a half-pad and a full-pad, over a 12-week period among female recreational road cyclists. Reducing the foam thickness in the crotch area of the pad does not change sensory manifestations, i.e. discomfort, wetness perception, texture-, and thermal-sensation as well as wear discomfort. Abbreviations: CS-Q: online Cycling bib Shorts Questionnaire; VADER: Valence Aware Dictionary and sEntiment Reasoner.

Personalized survival probabilities for SARS-CoV-2 positive patients by explainable machine learning.

Interpretable risk assessment of SARS-CoV-2 positive patients can aid clinicians to implement precision medicine. Here we trained a machine learning model to predict mortality within 12 weeks of a first positive SARS-CoV-2 test. By leveraging data on 33,938 confirmed SARS-CoV-2 cases in eastern Denmark, we considered 2723 variables extracted from electronic health records (EHR) including demographics, diagnoses, medications, laboratory test results and vital parameters. A discrete-time framework for survival modelling enabled us to predict personalized survival curves and explain individual risk factors. Performance on the test set was measured with a weighted concordance index of 0.95 and an area under the curve for precision-recall of 0.71. Age, sex, number of medications, previous hospitalizations and lymphocyte counts were identified as top mortality risk factors. Our explainable survival model developed on EHR data also revealed temporal dynamics of the 22 selected risk factors. Upon further validation, this model may allow direct reporting of personalized survival probabilities in routine care.

Sitting dynamics during computer work are age-dependent.

This laboratory study aimed to characterize the dynamics of sitting during a 40 min computer task in 20 younger (YG) and 18 older (OG) computer users. The position of the center of pressure (COP) in anterior-posterior (AP) and medial-lateral (ML) direction was computed. The range, velocity, area, standard deviation (SD) and sample entropy (SaEn) values were extracted. The range, velocity and area of the COP displacement were larger in the AP while the SD and SaEn were respectively larger and smaller in both AP and ML for the OG than the YG. The findings revealed altered dynamics of sitting among older computer users.