Congenital heart defects in recurrent reciprocal 1q21.1 deletion and duplication syndromes: Rare association with pulmonary valve stenosis

Microdeletion 1q21.1 (del 1q21.1) and the reciprocal microduplication 1q21.1 (dup 1q21.1) are newly recognized genomic disorders, characterized by developmental delay, dysmorphic features and congenital malformations. Congenital heart defect (CHD) is a major feature of del 1q21.1, and has been occasionally reported in dup 1q21.1. We report here a family segregating del 1q21.1 in 3 members. Two of the affected family members had CHD, including the proband with syndromic atrial septal defect, pulmonary valve stenosis (PVS), and muscular ventricular septal defects, and the maternal uncle with non-syndromic PVS. This finding prompted investigation of the role of recurrent rearrangements of chromosome 1q21.1 in the pathogenesis of PVS. We gathered 38 patients with PVS (11 syndromic and 27 non-syndromic), and searched for genomic rearrangements of 1q21.1. A dup 1q21.1 was detected in a single sporadic non-syndromic patient. Review of the CHDs in published del 1q21.1 and dup 1q21.1 subjects showed a great heterogeneity in anatomic types. In conclusion, the present family illustrates recurrent CHD in del 1q21.1, expressing either as syndromic in one family member or as non-syndromic in the another one. The spectrum of CHDs associated with del 1q21.1 and dup 1q21.1 can occasionally include PVS.     

Microbiome analysis revealing microbial interactions and secondary bacterial infections in COVID-19 patients comorbidly affected by Type 2 diabetes

The mortality of coronavirus disease 2019 (COVID-19) disease is very high among the elderly or individuals having comorbidities such as obesity, cardiovascular diseases, lung infections, hypertension, and/or diabetes. Our study characterizes the metagenomic features in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients with or without type 2 diabetes, to identify the microbial interactions associated with its fatal consequences.This study compared the baseline nasopharyngeal microbiome of SARS-CoV-2-infected diabetic and nondiabetic patients with controls adjusted for age and gender. The metagenomics based on next-generation sequencing was performed using Ion GeneStudio S5 Series and the data were analyzed by the Vegan-package in R. All three groups possessed significant bacterial diversity and dissimilarity indexes (p < 0.05). Spearman's correlation coefficient network analysis illustrated 183 significant positive correlations and 13 negative correlations of pathogenic bacteria (r = 0.6–1.0, p < 0.05), and 109 positive correlations between normal flora and probiotic bacteria (r > 0.6, p < 0.05). The SARS-CoV-2 diabetic group exhibited a significant increase in pathogens and secondary infection-causing bacteria (p < 0.05) with a simultaneous decrease of normal flora (p < 0.05). The dysbiosis of the bacterial community might be linked with severe consequences of COVID-19-infected diabetic patients, although a few probiotic strains inhibited numerous pathogens in the same pathological niches. This study suggested that the promotion of normal flora and probiotics through dietary supplementation and excessive inflammation reduction by preventing secondary infections might lead to a better outcome for those comorbid patients.     

Effect of chemodenervation on the cerebral vascular and microvascular response to hypoxia.

This study evaluated the effect of bilateral carotid chemodenervation on the cerebrovascular response to hypoxia in conscious rats. Cerebral blood flow was measured using 4-iodo[N-methyl-14C]antipyrine, and the total and perfused microvasculature was studied by injection of fluorescein isothiocyanate dextran and alkaline phosphatase staining. To maintain constant PCO2, hypoxia was achieved in chemoreceptor-intact rats by the use of 4% CO2-8% O2-88% N2 and in chemodenervated rats by the administration of 8% O2-92% N2. Blood gas and hemodynamic parameters were similar in the two groups of rats. Chemodenervation had no significant effect on either resting blood flow or the perfused microvasculature during normoxia. A significant increase in cerebral blood flow (from 71 +/- 3 to 138 +/- 9 ml/min/100 g in control and from 91 +/- 5 to 127 +/- 7 ml/min/100 g in chemodenervated rats) and in the percent of cerebral arterioles and capillaries perfused occurred in both hypoxic control and chemodenervated rats. In chemoreceptor-intact rats, the greatest increase in blood flow and in perfused microvasculature occurred in caudal structures (medulla and pons) in comparison with rostral structures (cortex, thalamus, and hypothalamus). In chemodenervated rats, a similar increase in blood flow and perfused microvasculature occurred in all brain regions, with no regional differences. Thus, chemodenervation did not affect the overall cerebral blood flow or the microvascular response to hypoxia; however, rostral-to-caudal regional differences in the hypoxic response were lost after chemodenervation.     

Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants

Objective:

To evaluate the serum levels of zinc and copper in epileptic children during the long-term treatment of anticonvulsant drugs and correlate this with healthy subjects.

Methods:

A hospital-based group matched case-control study was conducted in the Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt between November 2013 and October 2014. Ninety patients aged 7.1±3.6 years were diagnosed with epilepsy by a neurologist. The control group was selected from healthy individuals and matched to the case group. Serum zinc and copper were measured by the calorimetric method using a colorimetric method kit.

Results:

The mean zinc level was 60.1±22.6 ug/dl in the cases, and 102.1±18 ug/dl in the controls (p<0.001). The mean copper level was 180.1±32.4 ug/dl in cases compared with 114.5±18.5 ug/dl in controls (p<0.001).

Conclusion:

Serum zinc levels in epileptic children under drug treatment are lower compared with healthy children. Also, serum copper levels in these patients are significantly higher than in healthy people. No significant difference in the levels of serum copper and zinc was observed in using one drug or multiple drugs in the treatment of epileptic patients.Epilepsy is a common neurological disorder with heterogeneous nature affecting 50 million people world wide, with more than 85% living in the developing world, and it begins in childhood in more than half of the cases. An estimated 4.7 million people with epilepsy live in the Eastern Mediterranean Region.1 The prevalence of epilepsy in Egypt is not accurately determined, although some studies reported that the lifetime prevalence rate of epilepsy is 12.67/1000.2 Epilepsy is a disorder of brain electrical activity that may lead to recurrent seizures. The type of seizure depends on the part of the brain involved, and various causes can lead to seizures. The absence of a specific cause of the seizures is called primary or idiopathic epilepsy.3 Some of the main causes of epilepsy include: low oxygen during birth; head injuries that occur during birth or from accidents during youth or adulthood; brain tumors; genetic conditions that result in brain injury, such as tuberous sclerosis; infections such as, meningitis or encephalitis; stroke; or any other type of damage to the brain and abnormal levels of substances such as, sodium or blood sugar.4 Different mineral elements are critical for normal functioning of the central nervous system, and several studies have demonstrated that changes in different electrolytes of the body, such as sodium, potassium, magnesium, and the trace elements such as copper (Cu) and zinc (Zn) subsequently are effective on the incidence of convulsions and epilepsy.5 The routine treatment of the epilepsy is using anticonvulsant agents. The use of such drugs mainly controls the disease, or can reduce the times of the seizure. After initial recognition, approximately 70% of patients have controlled seizures with antiepileptic drugs (AEDs). Approximately 25% of patients with epilepsy do not have any observed improvement in the reduction of the amount of seizures, even when 2 or 3 AEDs are used. Some studies have shown the importance of a specific diet, hormones, and micronutrients in the management of patients with epilepsy.6 The aim of the present study was to evaluate serum levels of Cu and Zn in patients with epilepsy in long-term treatment with anticonvulsants and comparing this with healthy individuals.     

Whole Salivary Interleukin‐6 and Matrix Metalloproteinase‐8 Levels in Patients With Chronic Periodontitis With and Without Prediabetes

Background: The cytokine profile in unstimulated whole saliva (UWS) of patients with prediabetes and chronic periodontitis (CP) remains uninvestigated. The aim of this study is to assess interleukin (IL)‐6 and matrix metalloproteinase (MMP)‐8 levels in UWS of patients with CP with and without prediabetes. Methods: Eighty‐eight males (aged 39 to 51 years) were divided into three groups: group 1: 28 patients with CP and prediabetes; group 2: 30 patients with CP and without prediabetes; and group 3: 30 controls. Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels, periodontal parameters (plaque index, bleeding on probing, probing depth, attachment loss, and marginal bone loss), and number of missing teeth were recorded. UWS samples were collected, and UWS flow rate (UWSFR) was measured. IL‐6 and MMP‐8 were measured in UWS using enzyme‐linked immunosorbent assay. P values <0.05 were considered statistically significant. Results: Mean FBG and HbA1c levels were significantly higher in group 1 (119.3 ± 3.1 mg/dL and 6.1% ± 0.2%) than group 2 (80.1 ± 3.5 mg/dL and 4.8% ± 0.5%; P <0.001) and group 3 (75.3 ± 2.2 mg/dL and 4.3% ± 0.2%; P <0.05). UWSFR was significantly higher in groups 2 (0.53 ± 0.1 mL/minute; P <0.05) and 3 (0.51 ± 0.1 mL/minute; P <0.01) than group 1 (0.33 ± 0.05 mL/minute). Periodontal parameters were worse in group 1 (P <0.05) and group 2 (P <0.05) than group 3. There was no difference in periodontal parameters, numbers of missing teeth, or salivary IL‐6 and MMP‐8 levels between patients in groups 1 and 2. Conclusion: Salivary IL‐6 and MMP‐8 levels are elevated in patients with CP with and without prediabetes.     

Dynamic MRI of breast hardness following radiation treatment

PURPOSE: To evaluate functional microvascular characteristics of breast induration several years after radiation treatment using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) techniques. MATERIALS AND METHODS: Fifteen women with moderate or marked breast induration after surgery and radiotherapy for breast cancer (2-15 years) were examined. Images of the irradiated breast (boost and nonboost sites) on short tau inversion recovery (STIR) and DCE-MRI sequences were subjectively evaluated for edema and the presence of enhancement and compared to the contralateral normal breast. Quantitative enhancement parameters-percent enhancing pixels, transfer constant (K(trans)), rate constant (k(ep)), leakage space (v(e)), and maximum contrast medium accumulation (MCMA)-were also compared. RESULTS: No tumor recurrence was seen. Fat necrosis was seen in 2/15 cases. Increased parenchymal edema at the electron boost site was seen in 12/14 patients. Greater enhancement in the irradiated breast was seen in 11/14 evaluable patients. Kinetic parameter estimates including K(trans) were similar except for percent enhancing pixels, which was greater in the irradiated breast at both boost and nonboost sites (P = 0.03 and 0.04, respectively). v(e) and MCMA estimates were greater in breasts with marked induration compared to moderate grades (P = 0.002 and 0.01, respectively). CONCLUSION: Parenchymal edema may be an important contributor to palpable induration several years after breast radiotherapy. Increased fluid content may be related to increased numbers of perfused microvessels and/or impaired lymphatic drainage.     

Detection of hypervascular hepatocellular carcinoma with dynamic magnetic resonance imaging with simultaneously obtained in-phase and opposed-phase echo images

PURPOSE: The technique of double-phase echo chemical shift gradient-echo magnetic resonance (MR) imaging with the fast low-angle shot sequence (double-echo FLASH) provides in-phase and opposed-phase (double-phase) images simultaneously. The purpose of this study was to assess whether the dynamic study with a combination of in-phase and opposed-phase (double-phase) echo images improves the detectability of hypervascular hepatocellular carcinoma (HCC) compared with that with either in-phase or opposed-phase images alone. METHOD: Thirty-seven patients with 107 hypervascular HCCs who underwent the whole-liver double-phase echo dynamic MR imaging were enrolled in the study. Three radiologists blindly read in-phase images alone, opposed-phase images alone, and then double-phase images together. Sensitivity and positive predictive values as well as the areas below the alternative-free response receiver operating characteristic curve (Az values) for each imaging technique were calculated and compared statistically. RESULTS: The mean sensitivity, positive predictive values, and Az values for hypervascular HCCs were 51%, 77%, and 0.52 for in-phase imaging; 55%, 86%, and 0.58 for opposed-phase imaging; and 57%, 84%, and 0.63 for double-phase imaging, respectively. The mean sensitivity for opposed-phase imaging was significantly higher than that for in-phase imaging (P < 0.05), and the mean sensitivity for double-phase imaging was higher than that for in-phase imaging (P < 0.01). The mean Az value for the double-phase imaging was significantly higher than that for in-phase imaging (P < 0.01). CONCLUSION: Dynamic MR imaging with double-phase images was recommended for the detection of hypervascular HCC.     

Renal Tubular Epithelial Cell Self-Injury Through Fas/Fas Ligand Interaction Promotes Renal Allograft Injury

Tubular epithelial cells (TECs) coexpress Fas and Fas ligand (FasL), which could influence renal allograft injury. While TECs can resist apoptosis by Fas antibody, TEC apoptosis by contact with adjacent TECs has not been studied. Fas expression increased in TECs with cytokine treatment (IFN-gamma, TNF-alpha) while abundant FasL levels were not altered. Apoptosis (Annexin-V, DNA fragmentation) occurred in cytokine-treated TECs monolayers from C3H-HeJ mice by 24 h, but was absent in similarly treated TECs from Fas-deficient (lpr) or FasL-mutant (gld) mice, suggesting that 'self injury' occurred through Fas/FasL. Membrane labeling of TECs in cocultures confirmed that FasL-bearing TECs induced apoptosis when in contact with Fas-bearing TECs. Culturing TECs with allogeneic C57BL/6 (H-2b) splenocytes resulted in apoptosis and elimination of C3H-HeJ TECs by 48 h, with enhanced survival and reduced apoptosis using lpr or gld TECs. In a renal allograft model, survival of C57BL/6 recipients was greater (p < 0.05) and renal function improved (p < 0.001) using C3H-lpr or C3H-gld (H-2 k) donor kidneys compared with C3H-HeJ kidneys. These data demonstrate for the first time that cytokine-activated TECs can injure TECs through expression of functional FasL and Fas. We suggest that inhibition of TEC-TEC 'self injury' may be a novel strategy to augment renal allograft survival.     

Regional brain imaging of vesicular acetylcholine transporter using o‐[125I]iodo‐trans‐decalinvesamicol as a new potential imaging probe

In this study, the regional rat brain distribution of radioiodinated o‐iodo‐trans‐decalinvesamicol ([¹²⁵I]OIDV) was determined in vivo to evaluate its potential as a single‐photon emission computed tomography (SPECT) imaging probe for vesicular acetylcholine transporter (VAChT). Following intravenous injection, [¹²⁵I]OIDV passed freely across the blood–brain barrier and accumulated in rat brain. The accumulation of [¹²⁵I]OIDV in rat brain was significantly reduced by coadministration of (+/?)‐vesamicol (0.125 µmol). In contrast, the coadministration of σ‐receptor ligands, such as (+)‐pentazocine (0.125 µmol) as a σ‐1 receptor ligand and (+)?3‐(3‐hydroxyphenyl)‐N‐propylpiperidine (0.125 µmol) as a σ‐1 and σ‐2 receptor ligands, barely affected the accumulation of [¹²⁵I]OIDV in rat brain. These findings in vivo were corroborated by autoradiographic analysis ex vivo. The authors found that the tracer binds with pharmacological selectivity to VAChT in rat brain and predicted that it may likewise serve in translational SPECT imaging studies of this marker in the integrity of cholinergic innervations. Synapse 68:107–113, 2014. © 2013 Wiley Periodicals, Inc.