Neuroprotection of midbrain dopaminergic cells in MPTP‐treated mice after near‐infrared light treatment

This study explores whether near‐infrared (NIr) light treatment neuroprotects dopaminergic cells in the substantia nigra pars compacta (SNc) and the zona incerta‐hypothalamus (ZI‐Hyp) from degeneration in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated mice. BALB/c albino mice were divided into four groups: 1) Saline, 2) Saline‐NIr, 3) MPTP, 4) MPTP‐NIr. The injections were intraperitoneal and they were followed immediately by NIr light treatment (or not). Two doses of MPTP, mild (50 mg/kg) and strong (100 mg/kg), were used. Mice were perfused transcardially with aldehyde fixative 6 days after their MPTP treatment. Brains were processed for tyrosine hydroxylase (TH) immunochemistry. The number of TH⁺ cells was estimated using the optical fractionator method. Our major finding was that in the SNc there were significantly more dopaminergic cells in the MPTP‐NIr compared to the MPTP group (35%–45%). By contrast, in the ZI‐Hyp there was no significant difference in the numbers of cells in these two groups. In addition, our results indicated that survival in the two regions after MPTP insult was dose‐dependent. In the stronger MPTP regime, the magnitude of loss was similar in the two regions (≈60%), while in the milder regime cell loss was greater in the SNc (45%) than ZI‐Hyp (≈30%). In summary, our results indicate that NIr light treatment offers neuroprotection against MPTP toxicity for dopaminergic cells in the SNc, but not in the ZI‐Hyp. J. Comp. Neurol. 518:25–40, 2010. © 2009 Wiley‐Liss, Inc.     

Death following tonsillectomy in a child with Williams syndrome

Williams syndrome (WS) is an uncommon genetic syndrome due to a deletion of several genes on chromosome 7. The syndrome is associated with dysmorphic facies, neurological manifestations, idiopathic hypercalcemia, and cardiac abnormalities, particularly supravalvular aortic stenosis (SVAS). Children with Williams syndrome may have chronic serous otitis media and/or obstructive sleep apnea. Hyperacusis is also commonly seen in these children. We report a case of sudden death at the time of tonsillectomy/adenoidectomy and bilateral tympanostomy tube placement in a child with Williams syndrome. All children with Williams syndrome should have a thorough cardiac evaluation before undergoing general anesthesia for any otolaryngologic procedure.     

Gliomatosis cerebri: pitfalls in diagnosis.

We report two young patients with obscure presentations of gliomatosis cerebri. Initial CT scanning was inconclusive and in one case showed intraventricular haemorrhage, a feature not previously described. Magnetic resonance imaging was required to show the lesions with greater definition; however, in both cases, a biopsy was needed to confirm the diagnosis.     

Pitfalls in CT diagnosis of appendicitis: Pictorial essay

Despite the high diagnostic accuracy of CT for appendicitis, numerous pitfalls exist that may result in a misdiagnosis. This pictorial review outlines the potential pitfalls in the CT diagnosis of appendicitis that includes atypical position of the appendix and coexisting pathologies. Various mimickers of appendicitis and clinical dilemmas will be highlighted. Upon completion, the reviewer should have an improved ability to recognise appendicitis mimickers and identify equivocal or atypical findings.     

Novel coding,translation, and gene expression of a replicating covalently closed circular RNA of 220 nt

The highly structured (64% GC) covalently closed circular (CCC) RNA (220 nt) of the virusoid associated with rice yellow mottle virus codes for a 16-kDa highly basic protein using novel modalities for coding, translation, and gene expression. This CCC RNA is the smallest among all known viroids and virusoids and the only one that codes proteins. Its sequence possesses an internal ribosome entry site and is directly translated through two (or three) completely overlapping ORFs (shifting to a new reading frame at the end of each round). The initiation and termination codons overlap UGAUGA (underline highlights the initiation codon AUG within the combined initiation-termination sequence). Termination codons can be ignored to obtain larger read-through proteins. This circular RNA with no noncoding sequences is a unique natural supercompact “nanogenome.”Viroids and virusoids (viroid-like satellite RNAs) are typically small (220–450 nt) covalently closed circular (CCC) RNAs with no coding capacity (i.e., no genetic information) (1–3) and are the smallest replicating circular RNA pathogens (3, 4). Because of their circular nature, they usually replicate through a rolling circle model to produce larger concatemers (4, 5) which are then processed into monomeric forms with a self-splicing hammerhead ribozyme (virusoids and viroids in the Avsunviroidae family) (6, 7) or by cellular enzymes (8). We have previously reported (9) the characterization and nucleotide sequence of the smallest circular virusoid (220 nt), that of the rice yellow mottle virus (sobemovirus) (RYMV). Like other known virusoids, the small circular satellite of RYMV (scRYMV) depends on a helper virus RYMV for replication and packaging (9, 10).In silico translation of scRYMV revealed the presence of an unusual ORF capable of initiating translation from the AUG in the sequence UGAUGA of the 220-nt circular RNA by internal ribosome binding site (IRBS). As 220 is not an integer multiple of 3, after the first round of translation, the same circular sequence (or possibly the linear head-to-tail concatemers generated in vivo during rolling-circle replication) would be read in a different frame register. After the second round of translation, termination at the same initiation–termination sequence UGAUGA would result in the production of a highly basic 16-kDa protein with the N- and C-terminal halves of the protein encoded by the same 220-nt sequence but read in two distinct, totally overlapping frames. This virusoid could also suppress the leaky tandem termination codons (UGAUGA) to read the same sequence in a third frame and produce a new (18 kDa) read-through protein with an 18-aa C-terminal extension ended by a UAG codon. However, even the latter UAG termination codon may occasionally be ignored to generate longer proteins.In this report, we present evidence demonstrating that the putative ORF(s) deduced from the 220-nt circular RNA sequence as described above are indeed operational.Although this scRYMV RNA is classified as a virusoid, we report here that this virusoid is the only one so far found to encode for a protein. Modalities of initiation of translation (e.g., overlapped initiation and termination codons), the distinct N- and C-terminal halves of the 16-kDa protein translated from the same 220-nt circular sequence and the generation of read-through proteins were examined. We discuss the evolutionary implications of the genetic information and biological functions densely packed into a 220-nt nanogenome.     

Surveillance for metastatic hemangiopericytoma-solitary fibrous tumors-systematic literature review on incidence,predictors and diagnosis of extra-cranial disease

Glioblastoma is an aggressive brain malignancy with poor outcomes. Current standard of care involves surgery, radiotherapy and chemotherapy. Even with optimal treatment, 5-year survival rates are low. Many patients are unable to tolerate the considerable side effects that therapy involves and suffer from low quality of life. Anti-mitotic tumor treating fields have shown potential in treating glioblastoma with data suggesting that they prolong disease-free survival and overall survival. Novocure has marketed a device that generates these fields via externally placed electrodes. Incorporation of electric field therapy into GBM treatment has been somewhat slow, due to concerns about cost, practicality of its usage from a patient perspective, and hesitation of the medical and scientific community to embrace its unconventional mechanism. However, clinical trials have demonstrated this therapy has relatively minor side effects and high patient compliance. In this review, we explore the current state of this technology and discuss the benefits and limitations of tumor treating fields.     

Cranial fasciitis of the petrous temporal bone

Cranial fasciitis (CF) is a rare benign neoplastic lesion affecting the pericranium and deep fascia of the scalp. We report a case confined to the temporal bone, resembling a malignant destructive lesion. The mass was identified during myringotomy for recurrent unilateral otitis media. Biopsy was consistent with CF, which was partially resected. The patient has remained disease free for 12 months. Due to its rarity, no defined treatment algorithm for CF exists. Despite aggressive features on radiology, they may respond very well to partial resection.