The thermophilic fermentation of cellulosic material is generally regarded-as a result of the combined action of several species of bacteria, some of which attack the cellulose and others the sugars formed from the breakdown of the cellulose. Much effort has been spent on attempts to isolate the cellulose fermenters but very little attention has been paid to the associated sugar-fermenting organisms. Snieszko and Kimball (1933) isolated and described two types of such bacteria but gave no chemical data on the fermentation products formed. It, therefore, seemed desirable to make such a study. EXPERIMENTAL Medium and cultures The following medium was used in most of the experiments: Medium 1 NaNHiHPO4........
Overexpression of efflux pumps is an important mechanism of bacterial resistance that results in the extrusion of antimicrobial agents outside the bacterial cell. Inhibition of such pumps appears to be a promising strategy that could restore the potency of existing antibiotics. The NorA efflux pump of Staphylococcus aureus confers resistance to a wide range of unrelated substrates, such as hydrophilic fluoroquinolones, leading to a multidrug-resistance phenotype. In this work, approximately 150 heterocyclic boronic species were evaluated for their activity against susceptible and resistant strains of S. aureus. Twenty-four hit compounds, although inactive when tested alone, were found to potentiate ciprofloxacin activity by a 4-fold increase at concentrations ranging from 0.5 to 8 μg/mL against S. aureus 1199B, which overexpresses NorA. Boron-free analogues showed no biological activity, thus revealing that the boron atom is crucial for biological activity. This work describes the first reported efflux pump inhibitory activity of boronic acid derivatives.
Background
For the elderly population living at home, the implementation of professional services tends to mitigate the effect of loss of autonomy and increases their quality of life. While helping in avoiding social isolation, home services could also be associated to different healthcare pathways. For elderly patients, Emergency Departments (EDs) are the main entrance to hospital where previous loss of autonomy is associated to worst hospital outcomes. Part of elderly patients visiting EDs are still admitted to hospital for having difficulties coping at home without presenting any acute medical issue. There is a lack of data concerning elderly patients visiting EDs assisted by home services. Our aim was to compare among elderly patients visiting ED those assisted by professional home services to those who do not in terms of emergency resources’ use and patients’ outcome.
Methods
A multicenter, prospective cohort study was performed in 124 French EDs during a 24-h period on March 2016.Consecutive patients living at home aged ≥80 years were included. The primary objective was to assess the risk of mortality for patients assisted by professional home services vs. those who were not. Secondary objectives included admission rate and specific admission rate for “having difficulties coping at home”. The primary endpoint was in-hospital mortality. Cox proportional-hazards regression model was used to test the association between professional home services and the primary endpoint. Multi variables logistic regressions were performed to assess secondary endpoints.
Results
One thousand one hundred sixty-eight patients were included, median age 86(83–89) years old,32% were assisted by professional home services. The overall in-hospital mortality rate was 7%. Assisted patients had more investigations performed. Home services were not associated with increased in-hospital mortality (HR = 1.34;95%CI [0.68–2.67]), nor with the admission rate (OR = 0.92;95%CI [0.65–1.30]). Assisted patients had a lower risk of being admitted for “having difficulties coping at home” (OR = 0.59;95%CI [0.38–0.92]).
Conclusion
Professional home services which assist one-third of elderly patients visiting EDs, were not associated to lower in-hospital mortality or to an increased admission rate. Assisted patients were associated to a lower risk of being admitted for «having difficulties coping at home».Professional home services could result in avoiding some admissions and their corollary complications.
Trial registration
Clinicaltrial.gov - NCT02900391, 09/14/2016, retrospectively registered
Distal hereditary motor neuropathy represents a group of motor inherited neuropathies leading to distal weakness. We report a family of two brothers and a sister affected by distal hereditary motor neuropathy in whom a homozygous variant c.3G > T (p.1Met? ) was identified in the COQ7 gene. This gene encodes a protein required for Coenzyme Q10 biosynthesis, a component of the respiratory chain in mitochondria. Mutations of COQ7 were previously associated with severe multi-organ disorders characterized by early childhood onset and developmental delay.
Using patient blood sample and fibroblasts derived from a skin biopsy, we investigated the pathogenicity of the variant of unknown significance c.3G > T (p.1Met? ) in the COQ7 gene and the effect of Coenzyme Q10 supplementation in vitro.
We showed that this variation leads to a severe decrease in COQ7 protein levels in the patient’s fibroblasts, resulting in a decrease in Coenzyme Q10 production, and in the accumulation of 6-demethoxycoenzyme Q10, the COQ7 substrate. Interestingly, such accumulation was also found in the patient’s plasma. Normal Coenzyme Q10 and 6-demethoxycoenzyme Q10 levels were restored in vitro by using the Coenzyme Q10 precursor 2,4-dihydroxybenzoic acid, thus bypassing COQ7 requirement. Coenzyme Q10 biosynthesis deficiency is known to impair mitochondrial respiratory chain. Seahorse experiments showed that the patient’s cells mainly rely on glycolysis to maintain sufficient ATP production. Consistently, the replacement of glucose by galactose in the culture medium of these cells reduced their proliferation rate. Interestingly, normal proliferation was restored by Coenzyme Q10 supplementation in the culture medium, suggesting a therapeutic avenue for these patients.
Altogether, we have identified the first example of recessive distal hereditary motor neuropathy caused by a homozygous variation in the COQ7 gene, which should thus be included in the gene panels used to diagnose peripheral inherited neuropathies. Furthermore, 6-demethoxycoenzyme Q10 accumulation in the blood can be used to confirm the pathogenic nature of the mutation. Finally, supplementation with Coenzyme Q10 or derivatives should be considered to prevent the progression of COQ7-related peripheral inherited neuropathy in diagnosed patients.
Background. Left ventricular remodeling (LVR) that frequently occurs after acute myocardial infarction (AMI) is associated with an increased risk of heart failure and cardiovascular death. Although several risk factors have been identified, there is still no marker in clinical use to predict LVR. Plasma level of Coenzyme Q10 (CoQ10), that plays a key role in mitochondrial energy production and as an antioxidant, seems to be negatively correlated with left ventricular function after AMI. Objective. The goal of our study was to determine whether the plasma CoQ10 baseline concentrations at time of the ST-elevation myocardial infarction (STEMI) could predict LVR at 6 months follow-up. Methods. Sixty-eight patients who were admitted to hospital for STEMI and successfully revascularized with primary percutaneous coronary intervention (PPCI) were recruited. All patients underwent a 3D-echocardiography examination within the first 4 days after PPCI and 6 months later then divided in 2 groups based on the presence or not of LVR. Plasma CoQ10 level at the time of PPCI was determined using high performance liquid chromatography-tandem mass spectrometry (HPLC/MSMS). Results. While we found similar plasma CoQ10 concentrations compared to other studies, no association was evidenced between CoQ10 levels and LVR (p=0.89). Conclusion. We found no evidence for using plasma CoQ10 concentration as an early prediction marker of LVR after STEMI.
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