CTG expansion & haplotype analysis in DM1 gene in healthy Iranian population

Myotonic dystrophy type 1 (DM1) is due to an unstable expansion of CTG repeat in the DMPK gene (19q13.3). The CTG repeat is highly polymorphic (5 to 37) in healthy individuals. According to the hypothesis that expanded (CTG)n alleles originated from larger normal alleles, there may exist a correlation between the prevalence of DM1 and the frequency of large size normal alleles. Strong linkage disequilibrium between different length alleles and the three biallelic markers, Alu, Hinf1 and Taq1, has been reported. OBJECTIVE: To determine the distribution of normal alleles, the frequency of larger normal alleles and analysis of the three biallelic markers, in healthy Iranian controls. MATERIAL AND METHODS: Polymerase chain reaction (PCR) was conducted on two hundred unrelated healthy individuals from different ethnic groups living in Iran to determine the size of the alleles. Markers were analyzed by PCR/RFLP on 174 chromosomes from other control healthy individuals. RESULTS: Our data reveals that 23.7% of alleles had 5 CTG repeats and 7.2% of alleles had > 18 CTG repeats. The analysis of haplotypes revealed that 75% of CTG5 and 80% of CTG > 18 had the (+++) haplotype. CONCLUSION: The frequency of alleles with CTG > 18 in Iran is similar to that of Western Europe and Japan.     

Reflectance confocal microscopy may enhance the accuracy of histopathologic diagnosis: A case series

Although histopathology is the time‐honored gold standard diagnostic measure in dermatology, several factors may detract from an accurate microscopic diagnosis. Limiting factors include: human error, suboptimal biopsy‐site selection or biopsy technique, and inherent restrictions of vertical tissue sectioning that lead to incomplete microscopic evaluation of the lesion. Reflectance confocal microscopy (RCM) is a non‐invasive imaging tool that allows for the cellular‐level examination of the lesion, at a horizontal plane, which may complement the subsequent vertical histopathological tissue examination. Herein, we report a case series whereby prebiopsy RCM examination enhanced the accuracy of histopathological diagnosis or allowed for a critical appraisal of initial histopathological misdiagnosis.     

Angular versus spatial resolution trade‐offs for diffusion imaging under time constraints

Diffusion weighted magnetic resonance imaging (DW‐MRI) are now widely used to assess brain integrity in clinical populations. The growing interest in mapping brain connectivity has made it vital to consider what scanning parameters affect the accuracy, stability, and signal‐to‐noise of diffusion measures. Trade‐offs between scan parameters can only be optimized if their effects on various commonly‐derived measures are better understood. To explore angular versus spatial resolution trade‐offs in standard tensor‐derived measures, and in measures that use the full angular information in diffusion signal, we scanned eight subjects twice, 2 weeks apart, using three protocols that took the same amount of time (7 min). Scans with 3.0, 2.7, 2.5 mm isotropic voxels were collected using 48, 41, and 37 diffusion‐sensitized gradients to equalize scan times. A specially designed DTI phantom was also scanned with the same protocols, and different b‐values. We assessed how several diffusion measures including fractional anisotropy (FA), mean diffusivity (MD), and the full 3D orientation distribution function (ODF) depended on the spatial/angular resolution and the SNR. We also created maps of stability over time in the FA, MD, ODF, skeleton FA of 14 TBSS‐derived ROIs, and an information uncertainty index derived from the tensor distribution function, which models the signal using a continuous mixture of tensors. In scans of the same duration, higher angular resolution and larger voxels boosted SNR and improved stability over time. The increased partial voluming in large voxels also led to bias in estimating FA, but this was partially addressed by using “beyond‐tensor” models of diffusion. Hum Brain Mapp 34:2688–2706, 2013. © 2012 Wiley Periodicals, Inc.     

Methadone-induced hypoglycemia: A case report

Hypoglycemia is rare in patients without diabetes mellitus. Methadone is a synthetic μ-opioid receptor agonist used for cancer or non-cancer pain and the treatment of opioid dependence. Here, we report a case of a 31-year-old man who presented with recurrent hypoglycemic events that resolved on discontinuation of methadone. Thus, if hypoglycemia occurs while a patient takes methadone, the amount should be reduced or replaced with another opioid before a full investigation for inappropriate hyperinsulinism is initiated.     

Dimerization of 600 Da branched polyethylenimine improves β-lactam antibiotic potentiation against antibiotic-resistant Staphylococcus epidermidis and Pseudomonas aeruginosa

Antibiotic resistance is a growing concern in the medical field. Drug-susceptible infections are often treated with β-lactam antibiotics, which bind to enzymes known as penicillin-binding proteins (PBPs). When the PBPs are disabled, the integrity of the cell wall is compromised, leading to cell lysis. Resistance renders β-lactam antibiotics ineffective, and clinicians turn to be more effective, but often more toxic, antibiotics. An alternative approach is combining antibiotics with compounds that disable resistance mechanisms. Previously, we have shown that low-molecular-weight 600 Da branched polyethylenimine restores β-lactam susceptibility to Gram-positive and Gram-negative pathogens with antibiotic resistance. In this study, this approach is extended to the homodimers of 600 Da BPEI that have improved potentiation properties compared to monomers of 600 Da BPEI and 1200 Da BPEI. The homodimers are synthesized by linking two 600 Da BPEI molecules with methylenebisacrylamide (MBAA). The resulting product was characterized with FTIR spectroscopy, ¹H NMR spectroscopy, checkerboard microbroth dilution assays, and cell toxicity assays. These data show that the 600 Da BPEI homodimer is more effective than 1200 Da BPEI toward the potentiation of oxacillin against methicillin-resistant Staphylococcus epidermidis and the potentiation of piperacillin against Pseudomonas aeruginosa.