The water supply system as a potential source of fungal infection in paediatric haematopoietic stem cell units

Background: We conducted a prospective study to investigate the presence of microfungal contamination in the water supply system of the Oncology Paediatric Institute, São Paulo - Brazil after the occurrence of one invasive Fusarium solani infection in a patient after Haematopoietic Stem Cell Transplantation (HSCT). During a twelve-month period, we investigated the water supply system of the HSCT unit by monitoring a total of fourteen different collection sites.Methods: One litre of water was collected in each location, filtered through a 0.45 mu m membrane and cultured on SDA to detect the presence of filamentous fungi. Physicochemical analyses of samples were performed to evaluate the temperature, turbidity, pH, and the concentration of free residual chlorine.Results: Over the 12 months of the study, 164 samples were collected from the water supply system of the HSCT unit, and 139 of the samples tested positive for filamentous fungi (84.8%), generating a total of 2,362 colonies. Cladosporium spp., Penicillium spp., Purpureocillium spp. and Aspergillus spp. were ranked as the most commonly found genera of mould in the collected samples. of note, Fusarium solani complex isolates were obtained from 14 out of the 106 samples that were collected from tap water (mean of 20 CFU/L). There was a positive correlation between the total number of fungal CFU obtained in all cultures and both water turbidity and temperature parameters. Our findings emphasise the need for the establishment of strict measures to limit the exposure of high-risk patients to waterborne fungal propagules.Conclusions: We were able to isolate a wide variety of filamentous fungi from the water of the HSCT unit where several immunocompromised patients are assisted.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Med, Disciplina Infectol, BR-04024002 São Paulo, BrazilUniv Austral Chile, Inst Clin Microbiol, Valdivia, ChileUniv Antofagasta, Antofagasta, ChileUniversidade Federal de São Paulo, Inst Oncol Pediat, GRAACC, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Disciplina Infectol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Oncol Pediat, GRAACC, BR-04023062 São Paulo, BrazilFAPESP: 2005/02138-3CNPq: 133621/2007-3CAPES: PNPD 2312/2011CNPq: 150368/2005-4Web of Scienc

Nanomechanical Phenotypes in Cardiac Myosin-Binding Protein C Mutants That Cause Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a disease of the myocardium caused by mutations in sarcomeric proteins with mechanical roles, such as the molecular motor myosin. Around half of the HCM-causing genetic variants target contraction modulator cardiac myosin-binding protein C (cMyBP-C), although the underlying pathogenic mechanisms remain unclear since many of these mutations cause no alterations in protein structure and stability. As an alternative pathomechanism, here we have examined whether pathogenic mutations perturb the nanomechanics of cMyBP-C, which would compromise its modulatory mechanical tethers across sliding actomyosin filaments. Using single-molecule atomic force spectroscopy, we have quantified mechanical folding and unfolding transitions in cMyBP-C domains targeted by HCM mutations that do not induce RNA splicing alterations or protein thermodynamic destabilization. Our results show that domains containing mutation R495W are mechanically weaker than wild-type at forces below 40 pN and that R502Q mutant domains fold faster than wild-type. None of these alterations are found in control, nonpathogenic variants, suggesting that nanomechanical phenotypes induced by pathogenic cMyBP-C mutations contribute to HCM development. We propose that mutation-induced nanomechanical alterations may be common in mechanical proteins involved in human pathologies.J.A.C. acknowledges funding from the Ministerio de Ciencia e Innovación (MCIN) through grants BIO2014– 54768-P, BIO2017–83640-P (AEI/FEDER, UE), EIN2019–102966, RYC-2014–16604, and BFU2017–90692­ REDT, the European Research Area Network on Cardiovascular Diseases (ERA-CVD/ISCIII, MINOTAUR, AC16/00045), and the Comunidad de Madrid (consortium Tec4Bio-CM, S2018/NMT-4443, FEDER). This work was supported by NIH grants RM1 GM33289 and HL117138 to J.A.S.; a Stanford Dean’s Postdoctoral Fellowship to D.P. and N.N.; and a Stanford Maternal and Child Health Research Institute (MCHRI) Postdoctoral Fellowship (1220552–140-DHPEU) to N.N. Financial support to D.D.S. comes from Eusko Jaurlaritza (Basque Government) through the project IT1254–19, and grants RYC-2016–19590 and PGC2018–099321-B-I00 from the MCIN (FEDER). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), MCIN, and the Pro CNIC Foundation and was a Severo Ochoa Center of Excellence (SEV-2015–0505). We acknowledge funding from ISCIII to the Centro de Investigación Biomédica en Red (CIBERCV), CB16/11/00425. C.S.C. is the recipient of an FPI-SO predoctoral fellowship, BES-2016–076638. M.R.P. was the recipient of a Ph.D. fellowship from the Italian Ministry of Education, Universities and Research (MIUR). C.P.L. was a recipient of a CNIC Master Fellowship. We thank N. Vicente for excellent technical support (through grant PEJ16/MED/TL-1593 from Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid and the European Social Fund). We thank the Spectroscopy and Nuclear Magnetic Resonance Core Unit at CNIO for access to CD instrumentation and discussion about protein binding assays. We thank A. Thompson and S. Day for their insights. We thank all members of the Molecular Mechanics of the Cardiovascular System team for helpful discussions and the contribution of five anonymous reviewers.S

ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed

Relations between indicator quality properties, into two subtypes of brown soils in the province of Villa Clara

In this work the morphological and chemical characteristics are compared on the deck of the subtypes, fluffy and vertic, addition of relations between structural stability and organic matter in the soils evaluated. The samplings were conducted in soils under different management systems in the municipalities Ranchuelo and Santa Clara. The indicators studied were soil pH, calcium, value T, organic matter, structure factor and the stable aggregates. The results show that in both subtypes there is a strong relationship between soil properties, organic matter, structure factor and the stable aggregates which confirms the importance of these properties as indicators of the soil quality related to the management