Novel mutation of SLC37A4 in a glycogen storage disease type Ib patient with neutropenia,horseshoe kidney,and arteriovenous malformation: a case report

Glycogen storage disease type Ib (GSDIb) is an autosomal recessive disorder caused by mutations of SLC37A4 gene, which encodes glucose 6-phosphate translocase (G6PT). Malfunction of G6PT leads to excessive fat and glycogen in liver, kidney, and intestinal mucosa. The clinical manifestations of GSD1b include hepatomegaly, renomegaly, neutropenia, hypoglycemia, and lactic acidosis. Furthermore, the disorder may result in severe complications in long-term including inflammatory bowel disease (IBD), hepatocellular adenomas (HCA), short stature, and autoimmune disorders, which stem from neutropenia and neutrophil dysfunction. Here, we represent a novel mutation of SLC37A4 in a 5-month girl who has a history of hospitalizations several times due to recurrent infection and her early presentations were failure to thrive and tachypnea. Further investigations revealed mild atrial septal defect, mild arteriovenous malformation from left lung, esophageal reflux, Horseshoe kidney, and urinary reflux in this patient. Moreover, the lab tests showed neutropenia, immunoglobulin (Ig) G and IgA deficiency, as well as thrombocytosis. Whole exome sequencing revealed c.1245G?>?A P.W415 homozygous mutation in SLC37A4 gene and c.580G?>?A p.V1941 heterozygous mutation in PIK3CD gene. This study shows that manifestations of GSD1b may not be limited to what was previously known and it should be considered in a wider range of patients.

     

Circulating Levels of IL-1β, a Prothrombotic Cytokine,are Elevated in Unstable Angina Versus Stable Angina

Background: Multiple studies support a role for inflammation in the pathogenesis of coronary atherosclerosis and unstable cardiac syndromes. However, of the known proinflammatory cytokines, only elevated plasma levels of interleukin-6 have been linked to unstable angina. We sought to examine the plasma levels of other major proinflammatory cytokines in similar clinical settings and to determine the extent of the relationship between inflammation and unstable coronary syndromes by measuring the levels of various proinflammatory cytokines in patients with stable and unstable angina.Methods: We measured plasma levels of interleukin-1 beta (IL-1), tumor necrosis factor alpha (TNF-), and interleukin 6 (IL-6) in 97 patients: 67 with stable angina, 24 with unstable angina, and 15 healthy controls.Results: Mean levels of IL-1 were significantly higher in patients with unstable angina as compared to patients with stable angina (p = .009). Levels of IL-6 were significantly higher than control patients for both stable angina and unstable angina patients (p = .031 and .006, respectively). No significant differences were found in the levels of TNF-.Conclusions: Our results suggest that both IL-1 and IL-6 contribute to the pathogenesis of unstable angina, and that the profile of circulating plasma levels of proinflammatory cytokines differs in unstable angina from that in stable angina.Abbreviated Abstract. Multiple studies support a role for inflammation in the pathogenesis of coronary atherosclerosis and unstable cardiac syndromes. We measured plasma levels of interleukin-1 beta (IL-1), tumor necrosis factor alpha (TNF-), and interleukin 6 (IL-6) in patients with stable and unstable coronary syndromes. Levels of IL-1 and IL-6 were found to be elevated in patients with unstable coronary syndromes. No significant differences were found in the levels of TNF-. Our results suggest that both IL-1 and IL-6 contribute to the pathogenesis of unstable angina.     

The Le Fort system revisited: Trauma velocity predicts the path of Le Fort I fractures through the lateral buttress

OBJECTIVE:To examine the effect of trauma velocity on the pattern of Le Fort I facial fractures.METHOD:A retrospective medical record review was conducted on a consecutive cohort of craniofacial traumas surgically treated by a single surgeon between 2007 and 2011 (n=150). Of these cases, 39 Le Fort fractures were identified. Patient demographic information, method of trauma and velocity of impact were reviewed for these cases. Velocity of impact was expressed categorically as either ‘high’ or ‘low’: high-velocity fractures were those caused by a fall from >1 story or a motor vehicle collision; low-velocity fractures were the result of assaults with a blunt weapon, closed fist or falls from standing height. The vertical position of each fracture was measured at its point of entry on the lateral buttress and its point of exit on the piriform aperture. To allow for comparison across individuals, values were expressed as ratios based on their location on the face relative to these landmarks. A Wilcoxon rank-sum test was used to compare the fracture heights caused by high- and low-velocity trauma.RESULTS:The results revealed that high-velocity traumas to the face create Le Fort I fractures at a higher point in the lateral buttress compared with low-velocity traumas. There was no difference between heights at the piriform aperture.CONCLUSION:High-velocity trauma resulted in higher Le Fort I fracture patterns compared with low-velocity trauma.     

Continuous‐Flow Left Ventricular Assist Device Therapy in Patients With Preoperative Hepatic Failure: Are We Pushing the Limits Too Far?

The purpose of this study was to evaluate the effects and outcome of continuous‐flow left ventricular assist device (cf‐LVAD) therapy in patients with preoperative acute hepatic failure. The study design was a retrospective review of prospectively collected data. Included were 42 patients who underwent cf‐LVAD implantation (64.3% HeartMate II, 35.7% HeartWare) between July 2007 and May 2013 with preoperative hepatic failure defined as elevation of greater than or equal to two liver function parameters above twice the upper normal range. Mean patient age was 35 ± 12.5 years, comprising 23.8% females. Dilated cardiomyopathy was present in 92.9% of patients (left ventricular ejection fraction 17.3 ± 5.9%). Mean support duration was 511 ± 512 days (range: 2–1996 days). Mean preoperative laboratory parameters for blood urea nitrogen, serum creatinine, total bilirubin, and alanine aminotransferase were 9.5 ± 5.4 mg/dL, 110.3 ± 42.8 μmol/L, 51.7 ± 38.3 mmol/L, and 242.1 ± 268.6 U/L, respectively. All parameters decreased significantly 1 month postoperatively. The mean preoperative modified Model for Endstage Liver Disease excluding international normalized ratio score was 16.03 ± 5.57, which improved significantly after cf‐LVAD implantation to 10.62 ± 5.66 (P < 0.001) at 7 days and 5.83 ± 4.98 (P < 0.001) at 30 days postoperatively. One‐year and 5‐year survival was 75.9 and 48.1%, respectively. 21.4% of the patients underwent LVAD explantation for myocardial recovery, 16.7% were successfully transplanted, and 7.1% underwent LVAD exchange for device failure over the follow‐up period. Patients with preexisting acute hepatic failure are reasonable candidates for cf‐LVAD implantation, with excellent rates of recovery and survival, suggesting that cf‐LVAD therapy should not be denied to patients merely on grounds of “preoperative elevated liver enzymes/hepatopathy.”     

Activation of mitosis and angiogenesis in diabetes-impaired wound healing by processed human amniotic fluid

Background

Functional characterization of human amniotic fluid (AF) proteome, 845 proteins, has revealed that top three functions are cell proliferation, movement and differentiation, events fundamental to development, and tissue repair. Although these findings fortify the idea that AF components play roles in regeneration-like fetal wound healing, it is not known whether the components endure processing. Therefore, we processed AF and tested its effects on diabetes-impaired wound healing in an animal model.

Materials and methods

Through a germfree procedure, mature and premature AF samples were collected, respectively, from the mothers of full-term and preterm infants. Excisional wounds were generated on the dorsum of diabetic rats. Wounds were treated on day 3 and harvested on day 7 postwounding. Proliferating cell nuclear antigen and alpha–smooth muscles actin, markers for mitosis and angiogenesis, respectively, were assessed by in situ immunodetection method.

Results

Significant increases in the rate of wound closure and proliferating cell nuclear antigen–expressing cells were observed in AF-treated wounds when compared with that of sham and control wounds. Likewise, the number of large vessels was significantly increased in the wounds treated with the AF. However, population of myofibroblasts was not affected by the treatment. The mature and premature AF were almost equally effective.

Conclusions

Our data, for the first time, show that processed AF accelerates diabetes-impaired wound healing by activating mitosis and angiogenesis, indicating that bioactive molecules in AF may endure processing. We believe that processed forms of this naturally designed “Cocktail” of bioactive molecules may have multiple clinical applications.     

Electrically Contractile Polymers Augment Right Ventricular Output in the Heart

Research into the development of artificial heart muscle has been limited to assembly of stem cell‐derived cardiomyocytes seeded around a matrix, while nonbiological approaches to tissue engineering have rarely been explored. The aim of the study was to apply electrically contractile polymer‐based actuators as cardiomyoplasty for positive inotropic support of the right ventricle. Complex trilayer polypyrrole (PPy) bending polymers for high‐speed applications were generated. Bending motion occurred directly as a result of electrochemically driven charging and discharging of the PPy layers. In a rat model (n = 5), strips of polymers (3 × 20 mm) were attached and wrapped around the right ventricle (RV). RV pressure was continuously monitored invasively by direct RV cannulation. Electrical activation occurred simultaneously with either diastole (in order to evaluate the polymer's stand‐alone contraction capacity; group 1) or systole (group 2). In group 1, the pressure generation capacity of the polymers was measured by determining the area under the pressure curve (area under curve, AUC). In group 2, the RV pressure AUC was measured in complexes directly preceding those with polymer contraction and compared to RV pressure complexes with simultaneous polymer contraction. In group 1, the AUC generated by polymer contraction was 2768 ± 875 U. In group 2, concomitant polymer contraction significantly increased AUC compared with complexes without polymer support (5987 ± 1334 U vs. 4318 ± 691 U, P ≤ 0.01). Electrically contractile polymers are able to significantly augment right ventricular contraction. This approach may open new perspectives for myocardial tissue engineering, possibly in combination with fetal or embryonic stem cell‐derived cardiomyocytes.     

Detailed thrombogenicity phenotyping and 1 year outcomes in patients undergoing WATCHMAN implantation: (TARGET-WATCHMAN) a case–control study

Journal of Thrombosis and Thrombolysis - The relation of device related thrombosis (DRT) and major bleeding after left atrial appendage closure (LAAC) to laboratory thrombosis and hemostasis...     

Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions

An abundant presynaptic protein, alpha-synuclein, is centrally involved in the pathogenesis of Parkinson's disease. However, conflicting data exist about the normal function of alpha-synuclein, possibly because alpha-synuclein is redundant with the very similar beta-synuclein. To investigate the functions of synucleins systematically, we have now generated single- and double-knockout (KO) mice that lack alpha- and/or beta-synuclein. We find that deletion of synucleins in mice does not impair basic brain functions or survival. We detected no significant changes in the ultrastructure of synuclein-deficient synapses, in short- or long-term synaptic plasticity, or in the pool size or replenishment of recycling synaptic vesicles. However, protein quantitations revealed that KO of synucleins caused selective changes in two small synaptic signaling proteins, complexins and 14-3-3 proteins. Moreover, we found that dopamine levels in the brains of double-KO but not single-KO mice were decreased by approximately 20%. In contrast, serotonin levels were unchanged, and dopamine uptake and release from isolated nerve terminals were normal. These results show that synucleins are not essential components of the basic machinery for neurotransmitter release but may contribute to the long-term regulation and/or maintenance of presynaptic function.     

Prevalence of Psychiatric Symptoms and Mental Health Services in Students with Specific Learning Disabilities in Tehran,Iran

Children with specific learning disabilities are at a greater risk of mental health problems than their non-disabled peers. Further interventions and research will be required. This is a cross-sectional study. A sample of 107 students (7 to 11 years old) with specific learning disabilities were randomly selected from educational and rehabilitation settings in Tehran. The Child Symptom Inventory-4 (CSI-4) (parent checklist) was administered. Among children studied, 86 subjects (82.8 %) in some of the categories of psychiatric symptoms gained scores above the cut-off point. The most prevalent psychiatric symptoms were related to attention-deficit/hyperactivity disorder, generalized anxiety disorder and oppositional defiant disorder. There were not any statistically significant differences between the genders. In addition to direct education, 15 subjects (14 %) were receiving medication, 2 subjects (1.9 %) were receiving only occupational therapy, 2 subjects (1.9 %) were receiving only speech therapy, and 5 subjects (4.7 %) were receiving both occupational and speech therapy. The emphasis on considering co-morbid symptoms and usage of mental health services are important issues for students with specific learning difficulties.