Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Development of a single-tube, cell lysis-based, genus-specific PCR method for rapid identification of mycobacteria: optimization of cell lysis, PCR primers and conditions, and restriction pattern analysis

A single-tube PCR method was developed for efficient identification of nontuberculous mycobacteria (NTM) and their environmental isolates in about 3 h without conventional DNA isolation. The following three steps were optimized or developed: (i). a simple, 6-min direct cell lysis protocol as a PCR prestep for generation of DNA-template, (ii). an improved Mycobacterium-specific PCR amplification protocol with a broader species specificity using newly designed primers targeting a 228-bp region of the 65-kDa heat shock protein (hsp) gene and optimal PCR amplification conditions, and (iii). a genus-specific restriction analysis of the PCR product for conclusive identification of the unknown NTM isolates.     

Primary adenocarcinoma (intestinal type) of nasal septum--a case report

Primary nasal septal adenocarcinoma is a rare lesion. A sporadic case of septal adenocarcinoma in a 22 years old male is being described along with review of literature.     

Method for rapid identification and differentiation of the species of the Mycobacterium chelonae complex based on 16S-23S rRNA gene internal transcribed spacer PCR-restriction analysis

Members of the Mycobacterium chelonae complex (MCC), including M. immunogenum, M. chelonae, and M. abscessus, have been associated with nosocomial infections and occupational hypersensitivity pneumonitis due to metalworking fluid (MWF) exposures. In order to minimize these health hazards, an effective and rapid assay for detection of MCC species and differentiation of MCC species from other species of rapidly growing mycobacteria (RGM) and from one another is warranted. Here we report such a method, based on the variable 16S-23S rRNA gene internal transcribed spacer (ITS) region. Mycobacterium genus-specific primers derived from highly conserved sequences in the ITS region and the flanking 16S rRNA gene were used. Specificity of the primers was verified using the MCC member species, 11 non-MCC RGM species, 3 slow-growing mycobacterial (SGM) species (two strains each), and 19 field isolates, including 18 MCC isolates (from in-use MWF) and one non-MCC isolate (from reverse osmosis water). The ITS amplicon size of M. immunogenum varied from those of M. chelonae and M. abscessus. Sequencing of the approximately 250-bp-long ITS amplicons of the three MCC member species showed differences in 24 to 34 bases, thereby yielding variable deduced restriction maps. ITS PCR-restriction analysis using the in silico-selected restriction enzyme MaeII or HphI differentiated the three MCC members from one another and from other RGM and SGM species without sequencing. The enzyme MaeII discriminated all three member species; however, HphI could only differentiate M. immunogenum from M. chelonae and M. abscessus. Use of an optimized rapid DNA template preparation step based on direct cell lysis in the PCR tube added to the simplicity and adaptability of the developed assay.     

Primary carcinoma of the frontal sinus

A case of Primary Carcinoma of the Frontal Sinus.     

Soft tissue aneurysmal bone cyst of left hemithorax with review of literature

Soft tissue aneurysmal bone cysts (STABCs) are extremely rare extraosseous counterpart of aneurysmal bone cyst (ABC), with close resemblance to histo-morphologic characteristics of ABC. Here we would like to report a 13-year-old female patient, who presented with a large mass, occupying the entire left hemithorax. Patient underwent resection of the thoracic mass. On histopathological examination, it was found to be a soft tissue ABC. It is a very rare tumor and until date 28 cases have been reported in English literature, to the best of our knowledge. On review of the literature, we found this to be the first case of STABC reported in thoracic cavity. The objective of this case presentation is to provide information regarding clinical presentation, radiological and pathological features, and course of management for this rare disease. Soft tissue ABCs are a new class of tumors, so more extensive research is required to establish standard guidelines for their diagnosis and management, to yield better prognosis.     

Immune checkpoint inhibitor therapy-associated graft intolerance syndrome in a failed kidney transplant recipient

Immune checkpoint inhibitors (ICPIs) are monoclonal antibodies against inhibitory receptors on T cells resulting in anticancer activity. In kidney transplant (KT) recipients, ICPI use has been associated with acute allograft rejection. In failed allografts, however, the effects of ICPIs are unknown. We present a case of a 66-year-old man with a history of diabetes, renal cell cancer, left native nephrectomy, and end-stage kidney disease. He received a deceased donor KT which failed after 6 years due to biopsy-proven recurrent diabetic nephrosclerosis. He was started on hemodialysis and his immunosuppression was gradually weaned off. A year later, he was diagnosed with renal cell cancer in his right native kidney requiring nephrectomy. He later developed metastasis and was started on combination ICPIs. He developed hematuria, allograft pain, and malaise consistent with graft intolerance syndrome 28 days after starting ICPIs. Urine culture and cystoscopy were normal. A computed tomography scan of his abdomen revealed an enlarged allograft with patchy enhancement. After a multidisciplinary discussion, he underwent transplant nephrectomy. Histopathology showed chronic active T cell–mediated rejection. As ICPI use becomes prevalent, practitioners need to be aware of its potential complications among KT recipients both with functioning and failed allografts.     

Factors Influencing the Sex Ratio at Birth in India: A New Analysis based on Births Occurring between 2005 and 2016

Previous research on sex ratio at birth (SRB) in India has largely relied on macro‐analysis of census data that do not contain the breadth of factors needed to explain patterns in SRB. Additionally, no previous research has examined the differentiation of factors associated with SRB across birth orders, a key determinant in societies affected by son preference. This study aims to fill these gaps using micro‐data related to 553,461 births occurring between 2005 and 2016 collected as part of the 2015–2016 National Family Health Survey. Analyses used multivariable logistic regressions stratified by birth order to examine associations with SRB at the national level. The SRB at birth order 1 was outside the biological normal limit, and generally increased with birth order. First births in households with wealth in the middle and richest quintiles, with mothers who desired a higher ideal number of sons than daughters, and in lower fertility communities had a higher probability of being male. Most SRB correlates were visible at birth orders 3 or higher. Programs and policies designed to address India's male‐skewed SRB must consider the diverse factors that influence SRB, particularly for higher order births.