Search

Candida auris is an emerging drug-resistant pathogen associated with high mortality rates. This study aimed to explore the metabolic alterations and associated pathogenesis and drug resistance in fluconazole-treated Candida auris -host cell interaction. Compared with controls, secreted metabolites from fluconazole-treated C. auris and fluconazole-treated C. auris -host cell co-culture demonstrated notable anti- Candida activity. Fluconazole caused significant reductions in C. auris cell numbers and aggregated phenotype. Metabolites produced by C. auris with potential fungal colonization, invasion, and host immune evasion effects were identified. Metabolites known to enhance biofilm formation produced during C. auris -host cell interaction were inhibited by fluconazole. Fluconazole enhanced the production of metabolites with biofilm inhibition activity, including behenyl alcohol and decanoic acid. Metabolites with potential Candida growth inhibition activity such as 2-palmitoyl glycerol, 1-tetradecanol, and 1-nonadecene were activated by fluconazole. Different patterns of proinflammatory cytokine expression presented due to fluconazole concentration and host cell type (fibroblasts versus macrophages). This highlights the immune response's complexity, emphasizing the necessity for additional research to comprehend cell-type-specific responses to antifungal therapies. Both host cell interaction and fluconazole treatment increased the expression of CDR1 and ERG11 genes, both associated with drug resistance. This study provides insights into pathogenesis in C. auris due to host cell interaction and fluconazole treatment. Understanding these interactions is crucial for enhancing fluconazole sensitivity and effectively combating C. auris .

Purpose: Evaluate the relationship between different walking capacities and muscle strength in children with bilateral cerebral palsy (BCP) and assess these relationships in stronger and weaker children., Materials and Methods: Thirty-two children with spastic BCP were included. All participants walked under three speed conditions: comfortable, fast, and for a longer period (6 min). Walking speeds, Energy Expenditure Index (EEI), and lower limb muscle strength were measured. A global strength index (GSI) was computed as the sum of each muscle group strength. Pearson's coefficient and regression models were computed between walking capacities and the GSI., Results: GSI was correlated with the EEI and all walking speeds. Logarithmic regressions models explained between 24 and 34% of the variance of walking capacities. Then, the group was divided in two subgroups (weaker and stronger children). GSI was correlated with comfortable and endurance waking speed in weaker children, but not in stronger children., Conclusion: This study reports logarithmic relationship between muscle strength and walking capacities in children with BCP. The subgroup analysis implies that muscle strength has an impact on walking capacities solely in weaker children, suggesting that muscle strength must be preserved and reinforced in interventions targeting motor function in weaker children with BCP.Implications for rehabilitationIn a sample of children with spastic bilateral cerebral palsy, this study shows that global muscle strength is associated with walking capacities and the relationship seems more complex than linear.Based on the results, interventions should focus on maintaining or improving muscle strength in weaker children as no association was observed between muscle strength and walking capacities in stronger children.In stronger children, intervention should focus on factors other than muscle strength as it does not influence walking capacities.Based on this study, a more accurate screening of children who could benefit from strength training could be completed by initial global muscle strength.

Background: Arthrogryposis multiplex congenita is a term used to describe congenital contractures in at least two body parts with an overall prevalence of 1 in 3000 live births. It is often caused by lack of fetal movement in utero and presents as contractures of varying severity, which may affect the upper and lower extremities, the spine and jaw. Currently, no practice recommendations exist to inform best clinical practice for arthrogryposis multiplex congenita. Purpose: To identify the needs surrounding rehabilitation as experienced by youth with arthrogryposis multiplex congenita, caregivers, and clinicians and to propose solutions to develop family- and client-centred rehabilitation recommendations. Materials and methods: A modified experience-based co-design methodology was used where qualitative interviews were conducted with key stakeholders. Results: Twenty-seven participants completed the interviews and demographic information was collected where early-active rehabilitation began at birth in most cases and became less frequent through adolescence. Three overarching themes were determined for each stakeholder group. Conclusions: All participants reported that early-active rehabilitation is beneficial as it helps determine future treatments. Transition times and participation need to be at the center of interventions to ensure that the needs of youth with arthrogryposis multiplex congenita are being met. The development a condition-specific outcome-measure and rehabilitation practice recommendations will assist clinicians in addressing the needs of youth with arthrogryposis multiplex congenita.Implications for rehabilitationArthrogryposis multiplex congenita presents in at least two different areas of the body as multiple congenital contractures of varying severity which may affect the upper and lower extremities, spine and jaw.Youth with arthrogryposis multiplex congenita identified participation as an essential component of their life, however caregivers and clinicians did not emphasize this need.Gathering information from different stakeholders is important to ensure varying needs are addressed.Rehabilitation was reported to be beneficial from early childhood to late adolescence by youth, caregivers, and clinicians.Frequency of rehabilitation diminished over time, emphasizing the need for continued follow-up into adolescence.

Objectives: Limb lengthening by distraction osteogenesis is a technique widely used to treat limb length discrepancy resulting from trauma, congenital limb defects and long bone non-union. For decades, patients have resorted to the Ilizarov apparatus, prone to pin tract infections and scarring. Although implantable lengthening nails have reduced the incidence of complications, they are not applicable in pediatric patients with open growth plates. The aim of this project is to design a remote-controlled internal lengthening device suitable for implantation in children., Methods: The proposed device has the form of an internal remote-controlled telescopic lengthening plate, screwed to the lateral side of the bone with locking screws. This is appropriate for use with pediatric patients. It has been tested on an experimental bench which has the form of a vertically sliding platform, on which were stacked weights simulating soft-tissue resistance forces., Results: This internal lengthening plate generated distraction forces of up to 735 N on wooden and synthetic bones (Sawbones TM ). Furthermore, it maintained a constant distraction speed over the course of the procedure for a given weight., Conclusions: This device represents a major advancement in the field of pediatric limb-lengthening, addressing a demographic gap left open by current implantable devices.

In the European Working Party trial on High blood pressure in the Elderly, patients over 60 are randomly allocated either to receive diuretic capsules containing 25 mg hydrochlorothiazide and 50 mg triamterene or matching placebos. If the blood pressure remains high those receiving active diuretic treatment also receive methyldopa. Those receiving a placebo diuretic area given placebo methyldopa tablets. The study is double blind, started in 1974 and is still in progress. Three hundred and thirty-one patients have now been followed for 1 year and of these 190 have been followed for 2 and 90 for 3 years. After 1 year the serum cholesterol in the placebo group fell by an average of 10.4 mg/100 ml; over 2 years the fall was 16.0 mg/100 ml and over 3 years 20.8 mg/100 ml (6.7%). The corresponding results for the actively treated group were falls of 3.1 mg/100 ml; 20.3 mg/100 ml and 17.3 mg/100 ml (6.6%). Over a period of up to 3 years the average fall in cholesterol was 5.9 mg/100 ml/year in the placebo group and 5.0 mg/100 ml/year in the actively treated group. Thus the changes in serum cholesterol were similar whether the patients received active or placebo medication. In particular there was no evidence for an increase in cholesterol nor for a smaller decrease during diuretic therapy. In the actively treated group the fall in blood pressure in the more hypertensive patients was accompanied by a fall both in haematocrit and serum cholesterol. In patients with less severe hypertension, active treatment was not accompanied by a fall in either hematocrit or cholesterol. These different responses of serum cholesterol in the more and less severe hypertensives in the present study could explain some of the previous conflicting reports on the influence of diuretic treatment on serum cholesterol.