The antifungal mode of action of chitosan has been studied for the last 30 years, but is still little understood. We have found that the plasma membrane forms a barrier to chitosan in ...chitosan-resistant but not chitosan-sensitive fungi. The plasma membranes of chitosan-sensitive fungi were shown to have more polyunsaturated fatty acids than chitosan-resistant fungi, suggesting that their permeabilization by chitosan may be dependent on membrane fluidity. A fatty acid desaturase mutant of Neurospora crassa with reduced plasma membrane fluidity exhibited increased resistance to chitosan. Steady-state fluorescence anisotropy measurements on artificial membranes showed that chitosan binds to negatively charged phospholipids that alter plasma membrane fluidity and induces membrane permeabilization, which was greatest in membranes containing more polyunsaturated lipids. Phylogenetic analysis of fungi with known sensitivity to chitosan suggests that chitosan resistance may have evolved in nematophagous and entomopathogenic fungi, which naturally encounter chitosan during infection of arthropods and nematodes. Our findings provide a method to predict the sensitivity of a fungus to chitosan based on its plasma membrane composition, and suggests a new strategy for antifungal therapy, which involves treatments that increase plasma membrane fluidity to make fungi more sensitive to fungicides such as chitosan.
Objectives
To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD.
Design
A ...cross‐sectional study with a two‐step cluster analysis.
Settings
A tertiary referral multicenter study.
Participants
Nine hundred and eighty‐eight adult patients with unilateral MD. Main outcome measures: best predictors to define clinical subgroups with potential different aetiologies.
Results
We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni‐ and bilateral MD.
Conclusions
Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials.
We tested 294 domestic pet dogs in Mexico for neutralizing antibodies for mosquito-borne flaviviruses. We found high (42.6%) exposure to West Nile virus in Reynosa (northern Mexico) and low (1.2%) ...exposure in Tuxtla Gutierrez (southern Mexico) but very limited exposure to Aedes-borne flaviviruses. Domestic dogs may be useful sentinels for West Nile virus.
Overgrowth syndromes are characterized by global or localized disproportionate growth associated with other anomalies, including vascular malformations and neurological and/or visceral disorders. ...CLOVES (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined‐type Vascular malformations, Epidermal naevi, Scoliosis/Skeletal and spinal anomalies) is an overgrowth syndrome caused by mosaic activating mutation in gene PIK3CA, which gives rise to abnormal PI3K‐AKT‐mTOR pathway activation. These mutations are responsible for the clinical manifestations of the syndrome, which include low‐ and high‐flow vascular malformations, thoracic lipomatous hyperplasia, asymmetric growth, and visceral and neurological disorders. These common anomalies are illustrated with figures from two personal cases. Identification of the clinical and genetic characteristics of CLOVES syndrome is crucial for the differential diagnosis with other overgrowth syndromes, such as Proteus or Klippel–Trenaunay (K–T) syndromes, and for the therapeutic management of the different anomalies. In this context, a new entity comprising different syndromes with phenotypic mutations in PIK3CA has been proposed, designated PIK3CA‐related overgrowth spectrum (PROS), with the aim of facilitating clinical management and establishing appropriate genetic study criteria.
PIK3CA pathway and syndromes. Left asymmetric overgrowth and sandal gap.
Complete degradation of a pesticide mixture by a combination of a photo-Fenton pretreatment and an activated-sludge batch reactor is demonstrated. Four commercial pesticides, Laition, Metasystox, ...Sevnol and Ultracid were chosen for this experiment. The active ingredients are, respectively, dimethoate, oxydemeton-methyl, carbaryl and methidathion. The original pesticide concentration was 200
mg
L
−1. Biotreatment began after 31% photocatalytic mineralization, which after 5
h in a 6-L stirred batch-mode tank reactor with non-acclimated activated sludge, leaves the photo-Fenton effluent completely degraded. This biotreatment time is shorter than commonly found in municipal wastewater treatment plants (∼8–10
h). Therefore, the combined process is effective for rapid pesticide degradation in wastewater with complete removal of parent compounds and the associated DOC concentration. Nonetheless, assessment of this technology should take into account higher pesticide concentrations and how this factor affects both the photocatalytic and the biological oxidation.
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•DSP remains a bottleneck in the sustainable and economic production of PHAs.•The selection of DSP should be based on final product specification.•Green solvents have been found to ...dissolve scl and mcl-PHAs.•Chemical-free methods have great potential in large scale recovery of PHAs.
Bioplastics have emerged as a platform to reduce our dependence on fossil fuels. Polyhydroxyalkanoates (PHAs) are a family of biodegradable polyesters with large potential in consumer goods and medical applications. These polymers accumulate in prokaryotic microbes and their recovery is a challenging, often under explored, operation. In the past, oil-derived solvents and chemicals have been widely used as extracting agents, compromising the “environmentally-friendly” claim of bioplastics. Furthermore, the large amount of chemicals and solvents required at the industrial level would negatively impact the economics of the process. The present review presents the latest advances in the field of downstream operations for PHA recovery emphasizing those green technologies with scaling-up feasibility. As for the upstream and fermentation stages, the extraction process needs to be carefully optimized to accomplish a competitive production of PHAs.
The aim of the present study was to evaluate ischaemic reactive hyperaemia (IRH) in obstructive sleep apnoea (OSA) and its relationship with oxidative stress. We studied 69 consecutive patients ...referred to our Sleep Unit (Reina Sofia University Hospital, Cordoba, Spain). Patients with chronic diseases or those taking medication were excluded. IRH was assessed before and after polysomnography. Morning IRH and oxidative stress markers were compared between patients with (apnoea-hypopnoea index (AHI) ≥ 5) and without (AHI < 5) OSA. Measurements were repeated in 25 severe OSA patients after continuous positive airway pressure (CPAP) therapy. We included 46 OSA patients (mean ± sd AHI 49 ± 32.1) and 23 non-OSA subjects (AHI 3 ± 0.9). The OSA patients showed a significant worsening of morning IRH, and a significant increase in malondialdehyde and 8-hydroxydeoxyguanosine levels. Only the oxygen desaturation index independently explained morning IRH, while malondialdehyde levels showed a weak effect on IRH. In severe OSA patients, IRH improved significantly after CPAP treatment, as did malondialdehyde, 8-hydroxydeoxyguanosine and protein carbonyl levels. In OSA patients, endothelial dysfunction and oxidative stress were observed, and IRH worsened after sleep. The increase in oxidative stress was not associated with IRH, while intermittent hypoxia was strongly associated with IRH. In severe OSA patients, CPAP treatment improved oxidative stress and endothelial function.
We report on the detection of two series of harmonically related doublets in IRC +10216. From the observed frequencies, the rotational constant of the first series is B = 1380.888 MHz and that of the ...second series is B = 1381.512 MHz. The two series correspond to two species with a 2Σ electronic ground state. After considering all possible candidates, and based on quantum chemical calculations, the first series is assigned to MgC3N and the second to MgC4H. For the latter species, optical spectroscopy measurements support its identification. Unlike diatomic metal-containing molecules, the line profiles of the two new molecules indicate that they are formed in the outer layers of the envelope, as occurs for MgNC and other polyatomic metal-cyanides. We also confirm the detection of MgCCH that was previously reported from the observation of two doublets. The relative abundance of MgC3N with respect to MgNC is close to one while that of MgC4H relative to MgCCH is about ten. The synthesis of these magnesium cyanides and acetylides in IRC +10216 can be explained in terms of a two-step process initiated by the radiative association of Mg+ with large cyanopolyynes and polyynes followed by the dissociative recombination of the ionic complexes.
The aims of this study were to estimate the prevalence of familial cases in patients with Meniere's disease (MD) and to identify clinical differences between sporadic and familial MD. We recruited ...1375 patients with definite MD according to the American Academy of Otolaryngology‐Head and Neck Surgery criteria, obtaining the familial history of hearing loss or episodic vertigo by direct interview or a postal survey in 1245 cases in a multicenter study. Familial clustering was estimated by the recurrence risk ratio in siblings (λs) and offspring (λo) using intermediate and high prevalence values for MD in European population. A total of 431 patients (34%) reported a familial history of hearing loss or recurrent vertigo and 133 patients had a relative with possible MD. After clinical reevaluation, 93 relatives in 76 families were diagnosed of definite MD (8.4%), including three pairs of monozygotic twins. λs and λo were 16–48 and 4–12, respectively. We observed genetic heterogeneity, but most families had an autosomal dominant inheritance with anticipation. No clinical differences were found between sporadic and familial MD, except for an early onset in familial cases. We may conclude that MD has a strong familial aggregation and that sporadic and familial MDs are clinically identical.
Background: Excessive fructose intake causes metabolic syndrome in animals and can be partially prevented by lowering the uric acid level. We tested the hypothesis that fructose might induce features ...of metabolic syndrome in adult men and whether this is protected by allopurinol. Methods: A randomized, controlled trial of 74 adult men who were administered 200 g fructose daily for 2 weeks with or without allopurinol. Primary measures included changes in ambulatory blood pressure (BP), fasting lipids, glucose and insulin, homeostatic model assessment (HOMA) index, body mass index and criteria for metabolic syndrome. Results: The ingestion of fructose resulted in an increase in ambulatory BP (7±2 and 5±2 mm Hg for systolic (SBP) and diastolic BP (DBP), P<0.004 and P<0.007, respectively). Mean fasting triglycerides increased by 0.62±0.23 mmol l−1 (55±20 mg per 100 ml), whereas high-density lipoprotein cholesterol decreased by 0.06±0.02 mmol l−1 (2.5±0.7 mg per 100 ml), P<0.002 and P<0.001, respectively. Fasting insulin and HOMA indices increased significantly, whereas plasma glucose level did not change. All liver function tests showed an increase in values. The metabolic syndrome increased by 25–33% depending on the criteria. Allopurinol lowered the serum uric acid level (P<0.0001) and prevented the increase in 24-h ambulatory DBP and daytime SBP and DBP. Allopurinol treatment did not reduce HOMA or fasting plasma triglyceride levels, but lowered low-density lipoprotein cholesterol relative to control (P<0.02) and also prevented the increase in newly diagnosed metabolic syndrome (0–2%, P=0.009). Conclusions: High doses of fructose raise the BP and cause the features of metabolic syndrome. Lowering the uric acid level prevents the increase in mean arterial blood pressure. Excessive intake of fructose may have a role in the current epidemics of obesity and diabetes.
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