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Abstract Background Clinical dogma is that healthy urine is sterile and the presence of bacteria with an inflammatory response is indicative of urinary tract infection (UTI). Asymptomatic bacteriuria (ABU) represents the state in which bacteria are present but the inflammatory response is negligible. Differentiating ABU from UTI is diagnostically challenging, but critical because overtreatment of ABU can perpetuate antimicrobial resistance while undertreatment of UTI can result in increased morbidity and mortality. In this study, we describe key characteristics of the healthy and ABU urine microbiomes utilizing 16S rRNA gene (16S rDNA) sequencing and metaproteomics, with the future goal of utilizing this information to personalize the treatment of UTI based on key individual characteristics. Methods A cross-sectional study of 26 healthy controls and 27 healthy subjects at risk for ABU due to spinal cord injury-related neuropathic bladder (NB) was conducted. Of the 27 subjects with NB, 8 voided normally, 8 utilized intermittent catheterization, and 11 utilized indwelling Foley urethral catheterization for bladder drainage. Urine was obtained by clean catch in voiders, or directly from the catheter in subjects utilizing catheters. Urinalysis, urine culture and 16S rDNA sequencing were performed on all samples, with metaproteomic analysis performed on a subsample. Results A total of 589454 quality-filtered 16S rDNA sequence reads were processed through a NextGen 16S rDNA analysis pipeline. Urine microbiomes differ by normal bladder function vs. NB, gender, type of bladder catheter utilized, and duration of NB. The top ten bacterial taxa showing the most relative abundance and change among samples were Lactobacillales, Enterobacteriales, Actinomycetales, Bacillales, Clostridiales, Bacteroidales, Burkholderiales, Pseudomonadales, Bifidobacteriales and Coriobacteriales. Metaproteomics confirmed the 16S rDNA results, and functional human protein-pathogen interactions were noted in subjects where host defenses were initiated. Conclusions Counter to clinical belief, healthy urine is not sterile. The healthy urine microbiome is characterized by a preponderance of Lactobacillales in women and Corynebacterium in men. The presence and duration of NB and method of urinary catheterization alter the healthy urine microbiome. An integrated approach of 16S rDNA sequencing with metaproteomics improves our understanding of healthy urine and facilitates a more personalized approach to prevention and treatment of infection.

Background: The presence of white mater lesions in the central nervous system forces the differential diagnosis between multiple sclerosis (MS) and Anderson-Fabry disease (FD). Due to the type of inheritance, linked to the X chromosome, the diagnosis of FD is especially difficult in women. Tissue´s deposits of globotriaosylceramide (Gb3) are characteristics for FD and the deacylated form of Gb3 (Globotriaosylsphingosine or LysoGb3) is specific for this entity. Our objective is to investigate if concentrations of plasma Lyso-Gb3 are useful for ruling out the FD in a Spanish cohort of patients with a previous diagnosis of MS., Methods: we evaluated the α-galactosidase A enzymatic activity in 154 patients with a previous diagnosis of MS (93 women and 61 men): 103 Relapsing Remitting MS patients, 19 progressive MS patients and 32 with the clinically isolated syndrome. 116 (75% of the patients) were on MS disease modifying therapy. Enzymatic assay was completed in all cases and done on dried blood spot (DBS) samples. Subsequently the GLA gene was sequenced only in males and females who presented an enzymatic assay significantly lower than standardized controls (<50% for men and <75% for women). For subjects with GLA variants, plasma Lyso-Gb3 levels were performed by Tandem mass spectrometry from DBS, assuming a cut-off point for normality <3.5 ng/mL., Results: Genetic study was carried out in 30 women and 7 men; 8 of them had non-previous described GLA variants. After a thorough clinical examination no organic disease was found in any of the classical target organs. The study of Lyso-Gb3 concentrations in DBS was lower than 3.5 ng/mL, allowing us to discharge FD in all subjects and to consider these GLA variants like non pathologic., Conclusions: Lyso-Gb3 concentration in DBS is a useful tool to rule out Fabry disease in patients with MS. A concentration of LysoGb3 < 3.5 ng/mL rules out FD., Competing Interests: Declaration of Competing Interest Dr Torralba serves as a consultant for Genzyme Corporation and Shire Company and has received research grants, travel support and honoraria for speaking engagements from both companies. Dr Iñiguez has received research grants, travel support and honoraria for speaking engagements from Bayer, Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and TEVA. The rest of the authors declare the absence of conflict of interests., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Pneumocystis colonization is frequent in patients with chronic obstructive pulmonary disease (COPD) producing local and systemic inflammation. Heart failure is also a common comorbidity among patients with COPD. Heart failure is a chronic, frequent, and disabling condition with high morbidity and mortality, but with a modifiable course where endothelial dysfunction and pulmonary arterial hypertension have great importance. Animal models have shown that Pneumocystis infection can cause relevant functionally changes in vascular responses in the lung, promoting the development of pulmonary hypertension. Pneumocystis colonization could be a hidden cause of worsening heart failure through it capacity to induce inflammatory response with subsequent endothelial dysfunction and pulmonary hypertension. The aim of the present study was to investigate the prevalence of Pneumocystis jirovecii colonization in heart failure patients and its possible association with reduced or preserved ejection fraction. Methods: A cross-sectional study was carried out including 36 heart failure patients and 36 control cases. Identification of P. jirovecii colonization was performed by means of molecular techniques in oropharyngeal washing. Results: Pneumocystis -DNA was identified in oropharyngeal washing in 1 (2.7%) of 36 heart failure patients and in 3 (8.3%) of 36 controls. Conclusions: Pneumocystis colonization does not seem to have a role in the pathophysiology of heart failure., (Copyright © 2019 Merino-Casallo, Friaza, Menao, Domingo, Olivera, Calderón and Torralba.)

Mucopolysaccharidosis are multisystem diseases that require large multidisciplinary teams for their care. Specific recommendations are therefore needed for the transition from childhood to adulthood in this patient group. To overcome the barriers that might arise during the transition, the authors consider it essential to implement a flexible plan with a coordinator for the entire process, systematising the information through a standardised paediatric discharge report and educating the patient and their family about the disease, showing the characteristics of the healthcare system in this new stage. The final objective is that, once the transition to adulthood has been completed, the patient's autonomy and potential development are maximised and that the patient receives appropriate healthcare during this transition., (Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)