Already 40 genes have been identified for autosomal-recessive nonsyndromic hearing impairment (arNSHI); however, many more genes are still to be identified. In a Dutch family segregating arNSHI, ...homozygosity mapping revealed a 2.4 Mb homozygous region on chromosome 11 in p15.1-15.2, which partially overlapped with the previously described DFNB18 locus. However, no putative pathogenic variants were found in USH1C, the gene mutated in DFNB18 hearing impairment. The homozygous region contained 12 additional annotated genes including OTOG, the gene encoding otogelin, a component of the tectorial membrane. It is thought that otogelin contributes to the stability and strength of this membrane through interaction or stabilization of its constituent fibers. The murine orthologous gene was already known to cause hearing loss when defective. Analysis of OTOG in the Dutch family revealed a homozygous 1 bp deletion, c.5508delC, which leads to a shift in the reading frame and a premature stop codon, p.Ala1838ProfsX31. Further screening of 60 unrelated probands from Spanish arNSHI families detected compound heterozygous OTOG mutations in one family, c.6347C>T (p.Pro2116Leu) and c. 6559C>T (p.Arg2187X). The missense mutation p.Pro2116Leu affects a highly conserved residue in the fourth von Willebrand factor type D domain of otogelin. The subjects with OTOG mutations have a moderate hearing impairment, which can be associated with vestibular dysfunction. The flat to shallow "U" or slightly downsloping shaped audiograms closely resembled audiograms of individuals with recessive mutations in the gene encoding α-tectorin, another component of the tectorial membrane. This distinctive phenotype may represent a clue to orientate the molecular diagnosis.
Curdlan, a β-1,3/1,6-glucan found in Alcaligenes faecalis (A. faecalis) wall, activates innate and humoral immunity. The aim of this study is to evaluate whether pretreated rats with A. faecalis A12C ...could prevent sepsis disturbances and identify the immunomodulatory mechanisms involved. Experiments occurred in two stages: a survival study with 16 rats randomly divided into septic (SC) (n = 8) and septic pretreated (SA) (n = 8) groups and 45 rats divided into four groups: healthy (AGUSAN) (n = 9), septic (AGUIC) (n = 13), septic pretreated (AGUIA) (n = 14), and healthy pretreated (AGUSTO) (n = 9). Sepsis was induced by cecal ligation and puncture after 30 days of A. faecalis A12C pretreatment or without. SA group had a higher survival rate of 58% vs. 16% for SC group (P < 0.05). Overall, AGUIA showed better status than AGUIC (P < 0.01). Higher monocytosis was found in AGUIA and AGUSTO vs. AGUIC and AGUSAN, respectively (P < 0.05). A gradual increase in curdlan fecal concentration was observed in AGUIA during pretreatment. Fecal concentrations of Escherichia coli significantly decreased in AGUIA and AGUSTO. Bacterial load in urine, peritoneal lavage fluid (PLF), and bronchoalveolar lavage fluid (BALF) decreased (P < 0.05) in AGUIA vs. AGUIC. Finally, lower inflammation was observed in serum, BALF, and PLF, with reduced IL-6, IL-10, IL-1β, and TNF-α, along with less damage in lungs and peritoneum in AGUIA vs. AGUIC. These findings suggest the connection between curdlan-produced by A. faecalis A12C-with the immune system and the reduction in severity of experimental sepsis.
This article gives an overview of the different techniques used to identify, characterize, and quantify engineered nanoparticles (ENPs). The state-of-the-art of the field is summarized, and the ...different characterization techniques have been grouped according to the information they can provide. In addition, some selected applications are highlighted for each technique. The classification of the techniques has been carried out according to the main physical and chemical properties of the nanoparticles such as morphology, size, polydispersity characteristics, structural information, and elemental composition. Microscopy techniques including optical, electron and X-ray microscopy, and separation techniques with and without hyphenated detection systems are discussed. For each of these groups, a brief description of the techniques, specific features, and concepts, as well as several examples, are described.
To estimate the incidence rate and risk factors for diabetes in the Canary Islands.
A total of 5521 adults without diabetes were followed for a median of 3.5 years. Incident cases of diabetes were ...self-declared and validated in medical records. The following factors were assessed by Cox regression to estimate the hazard ratios for diabetes: impaired fasting glucose (5.6 mmol/l ≤ fasting glucose ≤ 6.9 mmol/l), BMI, waist-to-height ratio (≥ 0.55), insulin resistance (defined as triglycerides/HDL cholesterol ≥ 3), familial antecedents of diabetes, Canarian ancestry, smoking, alcohol intake, sedentary lifestyle, Mediterranean diet, social class and the metabolic syndrome.
The incidence rate was 7.5/10(3) person-years (95% CI 6.4-8.8). The greatest risks were obtained for impaired fasting glucose (hazard ratio 2.6; 95% CI 1.8-3.8), Canarian ancestry (hazard ratio 1.9; 95% CI 1.0-3.4), waist-to-height ratio (hazard ratio 1.7; 95% CI 1.1-2.5), insulin resistance (hazard ratio 1.5; 95% CI 1.0-2.2) and paternal history of diabetes (hazard ratio 1.5; 95% CI 1.0-2.3). The metabolic syndrome (hazard ratio 1.9; 95% CI 1.3-2.8) and BMI ≥ 30 kg/m(2) (hazard ratio 1.7; 95% CI 1.0-2.7) were significant only when their effects were not adjusted for impaired fasting glucose and waist-to-height ratio, respectively.
The incidence of diabetes in the Canary Islands is 1.5-fold higher than that in continental Spain and 1.7-fold higher than in the UK. The main predictors of diabetes were impaired fasting glucose, Canarian ancestry, waist-to-height ratio and insulin resistance. The metabolic syndrome predicted diabetes only when its effect was not adjusted for impaired fasting glucose. In individuals with Canarian ancestry, genetic susceptibility studies may be advisable. In order to propose preventive strategies, impaired fasting glucose, waist-to-height ratio and triglyceride/HDL cholesterol should be used to identify subjects with an increased risk of developing diabetes.
Abstract
Introduction and objectives
Ischemic heart disease is the cause of 50-60% of cases of heart failure with reduced left ventricular ejection fraction (HF-rEF). The impact of ischemic etiology ...on left ventricular ejection fraction (LVEF) improvement and prognosis remains unclear. Our main objective was to analyze the differential clinical profile between ischemic and non-ischemic etiology, as well as its medium-to-long term prognosis.
Methods
Prospective study of a cohort of patients with HF-rEF in real clinical practice. A comparative analysis was performed between patients with HF-rEF of non-ischemic etiology (Group 1) and ischemic etiology (Group 2). Clinical, analytical, echocardiographic and therapeutic variables were analyzed, and the medium-to-long term impact in terms of mortality and hospital readmissions for HF was evaluated.
Results
409 patients were analyzed. 276 patients (67.5%) had non-ischemic etiology and 133 patients (32.5%) had ischemic etiology. Group 2 was older (65.8±13.3vs70.8±10.3;p<0.001), more men (68.1%vs86.5%;p<0.001), higher prevalence of arterial hypertension (62.3%vs76.7%;p = 0.004), diabetes mellitus (38.8%vs67.7%; p<0.001), dyslipemia (52.4%vs82.7%;p<0.001), chronic kidney disease (34.4%vs56.4%;p<0.001), anemia (24.3%vs47.4%;p<0.001) and vascular comorbidity (25.7%vs54.9%;p<0.001) and lower prevalence of atrial fibrillation (56.2%vs44.4%;p = 0.025). In Group 2 there was a lower proportion of de novo HF (60.1%vs45.1%;p = 0.004) with longer HF evolution time (24.4±48.8vs61.5±89.3; p<0.001), a lower proportion of patients improving LVEF at follow-up (51.6%vs21.1%;p<0.001) and a higher baseline NTproBNP concentration 4463(IQR 1976-10431)vs5746(IQR 2336.5-13789);p = 0.039. Regarding baseline treatment, in Group 1 there was a higher prescription of mineralocorticoid receptor antagonists (78.3%vs63.9%;p = 0.002) and less ICD implantation (6.5vs14.3%;p = 0.01), with no differences in the rest of the treatment. With a mean follow-up of 60 months, Group 2 had a higher readmission rate (39%vs50.3%;p<0.01) and higher HF mortality (26.8%vs41%;p<0.01), with differences from early stages.
Conclusions
Patients with HF-rEF of ischemic etiology associate a greater number of comorbidities, a lower percentage of de novo HF, longer time of HF evolution, lower percentage of LVEF improvement and higher baseline NTproBNP.
Abstract
Background
Survivors of childhood cancer might be at increased risk of diastolic dysfunction at follow-up due to cardiotoxic treatment exposure. Although diastolic function assessment is ...challenging in this relatively young population, left atrial strain might provide a novel insight into this evaluation.
Purpose
To examine diastolic function in a cohort of long-term survivors of childhood acute lymphoblastic leukemia survivors using left atrial strain and conventional echocardiographic parameters.
Methods
Long-term survivors who were diagnosed at a single center between 1985-2015 and a control group of healthy siblings were recruited. Conventional diastolic function parameters and strain were compared, the latter measured during the three atrial phases: reservoir (PALS), conduit (LACS) and contraction (PACS). Inverse probability of treatment weighting was used to account for differences between the groups.
Results
90 survivors (24.6±9.7 years, time since diagnosis 18 11-26 years) and 58 controls were analyzed. PALS and LACS were significantly reduced compared to the control group: 46.4±11.2 vs 52.1±11.7 (p=0.003) and 32.5±8.8 vs 38.2±9.3 (p=0.003), respectively (figure 1B). Conventional diastolic parameters and PACS were similar between the groups (figure 1A). The reductions in PALS and LACS were associated to cardiotoxic treatment exposure in age and sex adjusted analysis (≥ moderate risk, low risk, controls): 45.4±10.5, 49.5±12.9, 52.1±11.7 (padj=0.003) and 31.7±9.0, 35.2±7.5, 38.2±9.3 (padj=0.001), respectively (figure 2).
Conclusions
Long-term childhood leukemia survivors showed a subtle impairment in diastolic function that was detected using atrial strain but not with conventional measurements. This impairment was more pronounced in those with higher cardiotoxic treatment exposure.Figure 1Figure 2
In a consanguineous Turkish family diagnosed with autosomal recessive nonsyndromic hearing impairment (arNSHI), a homozygous region of 47.4 Mb was shared by the two affected siblings on chromosome ...6p21.1-q15. This region contains 247 genes including the known deafness gene MYO6. No pathogenic variants were found in MYO6, neither with sequence analysis of the coding region and splice sites nor with mRNA analysis. Subsequent candidate gene evaluation revealed CLIC5 as an excellent candidate gene. The orthologous mouse gene is mutated in the jitterbug mutant that exhibits progressive hearing impairment and vestibular dysfunction. Mutation analysis of CLIC5 revealed a homozygous nonsense mutation c.96T>A (p.(Cys32Ter)) that segregated with the hearing loss. Further analysis of CLIC5 in 213 arNSHI patients from mostly Dutch and Spanish origin did not reveal any additional pathogenic variants. CLIC5 mutations are thus not a common cause of arNSHI in these populations. The hearing loss in the present family had an onset in early childhood and progressed from mild to severe or even profound before the second decade. Impaired hearing is accompanied by vestibular areflexia and in one of the patients with mild renal dysfunction. Although we demonstrate that CLIC5 is expressed in many other human tissues, no additional symptoms were observed in these patients. In conclusion, our results show that CLIC5 is a novel arNSHI gene involved in progressive hearing impairment, vestibular and possibly mild renal dysfunction in a family of Turkish origin.
Abstract
Background
The role of global longitudinal strain (GLS) in the long-term cardiac evaluation of childhood acute lymphoblastic leukemia (ALL) survivors is not clearly defined.
Purpose
To ...assess the prevalence of subclinical left ventricular systolic dysfunction (SLVD) in long-term survivors of ALL. We also aimed to compare echocardiographic measurements with a control group.
Methods
Patients <18 years of age diagnosed with ALL between 1985–2015 at our center were enrolled. Healthy siblings willing to participate were conformed the control group. GLS was measured with an automated software (AutoStrain, Tomtec). SLVD was defined as GLS<18.5% (absolute value) based on the lower limit of the 95% confidence interval in the control group. Group differences were accounted with nverse probability of treatment weighting.
Results
Of the 90 survivors included (37.8% female, time from diagnosis 18 11–26 years), 24 (26.6%) had SLVD. Left ventricular systolic but not diastolic measurements were reduced compared to the control group (Table 1). Predictors of GLS in the survivors were smoking (p=0.004) and history of hematopoietic stem-cell transplantation (p=0.042) (Table 2).
Conclusions
Over ¼ of childhood ALL survivors had abnormal GLS values after a median follow-up of 18 years. Left-ventricular systolic parameters were reduced compared to a control group.
Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Sociedad Española de Cardiología. Sociedad Andaluza de Cardiología.
A strain of
Alcaligenes faecalis
A12C (
A. faecalis
A12C) isolated from
Argyrosomus regius
is a probiotic in fish. Previous experiments showed that
A. faecalis
A12C had inhibitory effects on the ...growth of multidrug-resistant bacteria. We aimed to confirm whether
A. faecalis
A12C is safe and has adequate intestinal colonization in experimental rats, and evaluate its efficacy in an animal model of peritonitis
.
We used 30 male rats, randomly divided into 6 groups (
n
= 5): three groups (HA7, HA15, HA30) received
A. faecalis
A12C in drinking water (6 × 10
8
CFU/mL) for 7 days, and three control groups received drinking water only. All groups were evaluated at 7, 15, and 30 days. Survival after
A. faecalis
A12C administration was 100% in all groups. Mild eosinophilia (1.5%,
p
< 0.01) and increased aspartate aminotransferase (86 IU/L,
p
< 0.05) were observed in HA7, followed by progressive normalization. No histological signs of organ injury were found. We observed significant
E. coli
decline in faeces, parallel to an increase in
A. faecalis
A12C at 7 days.
E. coli
had a tendency to recover initial values, while
A. faecalis
A12C disappeared from the intestinal microbiota at 30 days. To evaluate its efficacy against peritonitis, we studied two additional groups of animals: IA group pretreated with
A. faecalis
A12C before
E. coli
intra-abdominal inoculation, and IC group inoculated with no
A. faecalis
A12C. We found an increase in C-reactive protein, alanine aminotransferase, urea, and eosinophils in IC animals when compared with IA. Peritonitis was more evident in IC than in IA animals. Our findings suggest that
A. faecalis
A12C altered clinically relevant parameters in sepsis and was associated with a lesser spread of infection.
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