GM3 synthase deficiency in non-Amish patients

PurposeBiallelic loss-of-function variants in ST3GAL5 cause GM3 synthase deficiency (GM3SD) responsible for Amish infantile epilepsy syndrome. All Amish patients carry the homozygous p.(Arg288Ter) variant arising from a founder effect. To date only 10 patients from 4 non-Amish families have been reported. Thus, the phenotypical spectrum of GM3SD due to other variants and other genetic backgrounds is still poorly known.MethodsWe collected clinical and molecular data from 16 non-Amish patients with pathogenic ST3GAL5 variants resulting in GM3SD.ResultsWe identified 12 families originating from Reunion Island, Ivory Coast, Italy, and Algeria and carrying 6 ST3GAL5 variants, 5 of which were novel. Genealogical investigations and/or haplotype analyses showed that 3 of these variants were founder alleles. Glycosphingolipids quantification in patients’ plasma confirmed the pathogenicity of 4 novel variants. All patients (N = 16), aged 2 to 12 years, had severe to profound intellectual disability, 14 of 16 had a hyperkinetic movement disorder, 11 of 16 had epilepsy and 9 of 16 had microcephaly. Other main features were progressive skin pigmentation anomalies, optic atrophy or pale papillae, and hearing loss.ConclusionThe phenotype of non-Amish patients with GM3SD is similar to the Amish infantile epilepsy syndrome, which suggests that GM3SD is associated with a narrow and severe clinical spectrum.     

Impaired Emotional Facial Expression Recognition in Alcohol Dependence: Do These Deficits Persist With Midterm Abstinence?

BACKGROUND: Emotional facial expression (EFE) decoding has been repetitively shown to be impaired in alcoholic inpatients. The present study aimed to replicate and extend previous findings on EFE recognition deficits in alcoholism. METHODS: Alcoholic and control participants' performances were compared on an EFE decoding task with a transversal and a longitudinal design. More specifically, 49 alcoholic individuals were recruited at a long-stay postdetoxification treatment center at the third or fourth week of their detoxification process. Twenty-two of them [abstinent alcoholic participants (AA)] were met at the end of their hospitalization process, 2 months later. The 27 remaining patients [dropping alcoholic participants(AD)] dropped out from treatment before the second meeting. A control group (C) of 22 participants was constituted, and assessed twice with the same average time as AA between the 2 assessments. The 3 groups were similar regarding age, sex, and education level. Participants were presented at both times with an EFE decoding test consisting of 16 photographs depicting EFE of happiness, anger, disgust, and sadness. RESULTS: The results corroborated previous findings highlighting more EFE decoding deficits in alcoholic participants compared with control participants, with no improvement after 3 months of abstinence. Transversal analyses further evidenced more EFE decoding difficulties in AD than in AA compared with controls. CONCLUSIONS: EFE decoding deficits in alcoholism persist with midterm abstinence. Alcoholic patients who dropped from treatment had the worst EFE decoding performance at baseline. Emotional facial expression decoding deficit could have a prognostic value in alcohol dependence.     

Optimal correlation between different instruments for Fibrotest-Actitest protein measurement in patients with chronic hepatitis C

OBJECTIVES: Combination of alpha 2-macroglobulin, haptoglobin, apolipoprotein-A1, gamma-glutamyl transpeptidase, total bilirubin and alanine aminotransferase measurements allows to determine the Fibrotest-Actitest score, an alternative to liver biopsy in hepatitis C virus infection. The aims of this study were to evaluate the analytical variability of the Fibrotest-Actitest proteins alpha 2-macroglobulin, haptoglobin and apolipoprotein-A1, and to assess their impact on the Fibrotest-Actitest scores.METHODS: We compared 129 sera from hepatitis C virus infected patients for alpha 2-macroglobulin, haptoglobin and apolipoprotein-A1 levels obtained with the Immage (Beckman-Coulter) and the BNProspec (Dade-Berhing) automates. We evaluated Fibrotest-Actitest results obtained with the two nephelemeters.RESULTS: Optimal correlation was found for alpha 2-macroglobulin (Y=1.05X + 0.01, correlation coefficient: 0.98) and haptoglobin (Y=1.05X - 0.07, correlation coefficient: 0.98). Apolipoprotein-A1 levels, as determined by Immage, were slightly lower than those obtained by BNProspec (Y=0.86X - 0.02, CC=0.95). When Fibrotest-Actitest scores obtained with the two protein measurements were compared adjusting for apolipoprotein-A1 from Immage, the concordance rate was 0.903+/-0.096, with only 2/107 patients showing minimal discordance>0.10 for Fibrotest, and 1.00+/-0.06 for Actitest, with no discordance>0.10.CONCLUSIONS: Measurement of apolipoprotein-A1, included in the Fibrotest-Actitest score, depends on the equipment used. Such discordance is of little clinical consequence for liver fibrosis evaluation in hepatitis C virus patients.     

Recurrent inverted duplication of 2p with terminal deletion in a patient with the classical phenotype of trisomy 2p23-pter

Inverted duplications with terminal deletions have been reported in an increasing number of chromosomes and are probably more frequent than suspected until recently. We describe the cytogenetic and molecular characterization of an inverted duplication of chromosome 2p in an 8-year-old girl. Firstly interpreted as partial duplication 2p, the rearrangement was in fact an inverted duplication associated with a terminal deletion of the short arm of the rearranged chromosome 2, the latter not being detectable by cytogenetic analysis. The complete karyotype was: 46,XX,add(2)(p23)dn.ish inv dup del(2)(:p23.2-->p25.3::p25.3-->qter) (wcp2+,N-MYC++,2pter-)dn. We precisely define the extension of both the duplication and the deletion using bacterial artificial chromosomes clones spanning the regions. The size of the inverted duplicated segment was estimated to be 28 Mb, spanning from 2p23.2 to 2p25.3, and an approximately 1.6 Mb segment at 2pter-p25.3 was deleted in the abnormal chromosome. The physical findings noted in our patient include prominent forehead, hypertelorism, flat nasal bridge, and low-set and large ears. In addition, she had congenital heart defect and scoliosis. Her psychomotor development was severely delayed from the beginning. All these clinical features are the same as observed for the typical trisomy 2p23-pter syndrome. The phenotypic effects of the terminal deletion of 2p in addition to the trisomy are discussed. This is the third patient presenting with a severe clinical phenotype and a de novo inv dup del (2p).     

MRI appearance of the distal insertion of the anterior cruciate ligament of the knee: an additional criterion for ligament ruptures

Objective

Anterior cruciate ligament tears are frequent and if not diagnosed may lead to relevant patient disability. Magnetic resonance imaging is the method of choice for the non-invasive diagnosis of these tears. Despite the high performance of this method some cases are challenging and the criteria described in the literature are not sufficient to reach a diagnosis. We propose a systematic method for the evaluation of anterior cruciate ligament tears based on the aspect of its distal portion.

Materials and methods

Magnetic resonance studies of 132 knees were evaluated in correlation with arthroscopy. The performance of the proposed method was compared with that of classic imaging signs of anterior cruciate ligament tear. The impact of image quality and reader expertise on the proposed method and the classic signs of tear were taken into account.

Results

This method had a sensitivity and specificity of 91.1% and 82.9% for the detection of abnormal ACLs. The interobserver agreement (kappa) of the proposed method was significantly higher than that of the classic signs at all levels of expertise (0.89 vs 0.76). This method was not influenced by image quality. Distal ACL analysis identified more partial tears and synovialization (granulation scar tissue) than the conventional method (71% vs 58.5% for partial tears and 83.5% vs 58.5% for synovialization).

Conclusion

The proposed classification has a high performance and reproducibility for the identification of abnormal anterior cruciate ligament. The results were influenced neither by the level of expertise of the readers nor by the image quality.     

Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes

Aims/hypothesis

MicroRNAs are key regulators of gene expression involved in health and disease. The goal of our study was to investigate the global changes in beta cell microRNA expression occurring in two models of obesity-associated type 2 diabetes and to assess their potential contribution to the development of the disease.

Methods

MicroRNA profiling of pancreatic islets isolated from prediabetic and diabetic db/db mice and from mice fed a high-fat diet was performed by microarray. The functional impact of the changes in microRNA expression was assessed by reproducing them in vitro in primary rat and human beta cells.

Results

MicroRNAs differentially expressed in both models of obesity-associated type 2 diabetes fall into two distinct categories. A group including miR-132, miR-184 and miR-338-3p displays expression changes occurring long before the onset of diabetes. Functional studies indicate that these expression changes have positive effects on beta cell activities and mass. In contrast, modifications in the levels of miR-34a, miR-146a, miR-199a-3p, miR-203, miR-210 and miR-383 primarily occur in diabetic mice and result in increased beta cell apoptosis. These results indicate that obesity and insulin resistance trigger adaptations in the levels of particular microRNAs to allow sustained beta cell function, and that additional microRNA deregulation negatively impacting on insulin-secreting cells may cause beta cell demise and diabetes manifestation.

Conclusions/interpretation

We propose that maintenance of blood glucose homeostasis or progression toward glucose intolerance and type 2 diabetes may be determined by the balance between expression changes of particular microRNAs.     

Use of a health information telephone line, Info-santé CLSC, for the surveillance of waterborne gastroenteritis

The increasing frequency of waterborne outbreaks demonstrates that classic indicators used for the surveillance of the microbiological quality of drinking water have several gaps and that routine public health surveillance seems insufficient to allow for the rapid detection of these outbreaks. The main objective of this study was to evaluate the possibility of using a regional health information telephone line, 'Info-Santé CLSC' (Info-Health Local Community Health Centre), for the surveillance of waterborne gastroenteritis. This study measured the incidence rate of calls for acute gastrointestinal illness (AGI) placed to the Info-Santé CLSC line, investigated the relationship between the frequency of calls for AGI placed to the Info-Santé CLSC line and the turbidity of the treated water in the Quebec City drinking water plant and evaluated the relevance and the conditions of use of the Info-Santé CLSC system for the surveillance of waterborne enteric illness. A relationship between the turbidity and the calls for AGI placed to Info-Santé CLSC line was observed. Significant time lags (11, 15 and 17 days prior to the outcome) were identified in the final model derived from a Poisson model using generalized additive models (GAM) as a time series analysis. Some recommendations to improve the system were formulated even though the system already seems to be useful for the surveillance of waterborne enteric diseases.     

Open-chest CPR improves survival and neurologic outcome following cardiac arrest

STUDY OBJECTIVE: To determine if 15 min of open-chest cardiac massage (OC-CPR) versus closed-chest compressions (CC-CPR) improves 72-h survival and neurologic outcome (behavioral and histologic) after 5 min of untreated cardiac arrest. METHODS: Mongrel dogs were anesthetized and instrumented. Cardiac arrest was induced by KCl injection and after a 5-min period of non-intervention, dogs were randomized to receive either CC-CPR (N = 7) or OC-CPR (N = 5) performed for 15 min. The dogs were then resuscitated and physiologic data was recorded. Surviving dogs were scored at 72 h using canine neurodeficit score of Safar et al. (NDS; 0 = behaviorally normal, 500 = brain death). Dogs that could not be resuscitated or died before 72 h were assigned a score of 500. Brain histology was performed on all survivors. RESULTS: All OC-CPR dogs were successfully resuscitated and were behaviorally normal at 72 h (NDS = 0). Histology in OC-CPR dogs showed little to no injury. Only three out of the seven CC-CPR dogs survived to 72 h. Of the survivors, one dog exhibited minor ataxia (NDS = 15), and two had incapacitating deficits (both NDS = 180). Two dogs died within 24 h after extubation, and one could not be resuscitated and the other could not be weaned from the ventilator (each NDS = 500). Histology of the CC-CPR survivors revealed moderate to severe lesions. NDS between groups was statistically significant (p < 0.0079). CONCLUSION: In our canine model of cardiac arrest, OC-CPR significantly improved 72-h survival and neurologic outcome when compared to CC-CPR.