Self-Mutilation in Neurodegeneration with Brain Iron Accumulation

Neurodegeneration with brain iron accumulation (NBIA) is the term applied to a heterogeneous group of disorders resulting in iron deposition in the basal ganglia. Well-known phenotypic features are progressive regression with extra pyramidal involvement and a variable course. A 10-year-old child born to consanguineous parents presented with progressive generalized opisthotonic dystonia, retrocollis, oromandibular dyskinesias, apraxia for swallowing, optic atrophy and severe self-mutilation of lips. MR imaging showed brain iron accumulation. Other causes of self-mutilation were excluded. Early infantile onset, ophisthotonic dystonia with oromandibular dyskinesias and characteristic MR images are suggestive of NBIA. There is only one case reported in the literature of self-mutilation in this condition.     

EGPred: prediction of eukaryotic genes using ab initio methods after combining with sequence similarity approaches

EGPred is a Web-based server that combines ab initio methods and similarity searches to predict genes, particularly exon regions, with high accuracy. The EGPred program proceeds in the following steps: (1) an initial BLASTX search of genomic sequence against the RefSeq database is used to identify protein hits with an E-value <1; (2) a second BLASTX search of genomic sequence against the hits from the previous run with relaxed parameters (E-values <10) helps to retrieve all probable coding exon regions; (3) a BLASTN search of genomic sequence against the intron database is then used to detect probable intron regions; (4) the probable intron and exon regions are compared to filter/remove wrong exons; (5) the NNSPLICE program is then used to reassign splicing signal site positions in the remaining probable coding exons; and (6) finally ab initio predictions are combined with exons derived from the fifth step based on the relative strength of start/stop and splice signal sites as obtained from ab initio and similarity search. The combination method increases the exon level performance of five different ab initio programs by 4%-10% when evaluated on the HMR195 data set. Similar improvement is observed when ab initio programs are evaluated on the Burset/Guigo data set. Finally, EGPred is demonstrated on an approximately 95-Mbp fragment of human chromosome 13. The list of predicted genes from this analysis are available in the supplementary material. The EGPred program is computationally intensive due to multiple BLAST runs during each analysis. The EGPred server is available at http://www.imtech.res.in/raghava/egpred/.     

Interleukin-1 receptor antagonist and interleukin-1β-511 gene polymorphisms among Egyptian children with febrile seizures

Febrile seizures (FSs) are the most common form of childhood seizures. The higher levels of pro-inflammatory cytokines in children may induce seizures, and alternatively, higher levels of anti-inflammatory cytokines may act as a defense mechanism against seizures. We aimed to investigate whether interleukin (IL)-1β-511 C/T (pro-inflammatory cytokine) (rs16944) and IL-1 receptor antagonist (IL-1Ra) (an anti-inflammatory cytokine) gene polymorphisms could be used as markers for prediction of susceptibility to FSs. The current study included 22 patients with FSs and 22 normal control subjects. All patients were subjected to thorough history taking, full neurological examination, electroencephalography, and peripheral blood sampling for genotype analyses. Detection of IL-1Ra gene polymorphisms was done using polymerase chain reaction (PCR), while a restriction fragment length polymorphism analysis of the PCR products was used for the detection of IL-1β-511 C/T gene polymorphisms. The mean age of onset of first febrile seizures was 15.7 months. Eighteen (81.8 %) cases had the criteria of complex FSs. Frequencies of alleles C and T for IL-1β-511 were 26/44 and 18/44, respectively, in FS patients and 22/44 for both in the control subjects. The CC genotype was significantly more common in the FS patients than in the control group. The IL-1Ra-I homozygote was more frequent in patients with FSs than in healthy controls. The IL-1Ra homozygous I/I and IL-1β-511 CC gene polymorphisms are associated with a higher susceptibility to febrile seizures, which may be useful markers for predicting the development of febrile seizures.     

Gender difference in antidepressant-related sexual dysfunction in Taiwan

Objective

Sexual dysfunction accompanied by depression may be altered by antidepressants. The effects of antidepressants on sexual dysfunction among males and females remain to be investigated.

Methods

Three groups of subjects, drug-free patients with depression (N= 125), medicated patients with depression (N= 145) and healthy volunteers (N= 255), were recruited. A Chinese version of the Changes in Sexual Functioning Questionnaire was employed to assess sexual function as the primary outcome.

Results

Drug-free depressed females and medicated depressed males had more sexual dysfunction than healthy controls. The desire for sexual behaviors among healthy females and medicated depressed females was higher than that of drug-free depressed females.

Conclusion

Depression and antidepressants may have different impacts on the sexual function of males and females.     

Tissue and Process Specific microRNA–mRNA Co-Expression in Mammalian Development and Malignancy

An association between enrichment and depletion of microRNA (miRNA) binding sites, 3′ UTR length, and mRNA expression has been demonstrated in various developing tissues and tissues from different mature organs; but functional, context-dependent miRNA regulations have yet to be elucidated. Towards that goal, we examined miRNA–mRNA interactions by measuring miRNA and mRNA in the same tissue during development and also in malignant conditions. We identified significant miRNA-mediated biological process categories in developing mouse cerebellum and lung using non-targeted mRNA expression as the negative control. Although miRNAs in general suppress target mRNA messages, many predicted miRNA targets demonstrate a significantly higher level of co-expression than non-target genes in developing cerebellum. This phenomenon is tissue specific since it is not observed in developing lungs. Comparison of mouse cerebellar development and medulloblastoma demonstrates a shared miRNA–mRNA co-expression program for brain-specific neurologic processes such as synaptic transmission and exocytosis, in which miRNA target expression increases with the accumulation of multiple miRNAs in developing cerebellum and decreases with the loss of these miRNAs in brain tumors. These findings demonstrate the context-dependence of miRNA–mRNA co-expression.     

Distal femur resection with endoprosthetic reconstruction: a long-term followup study

The distal femur is a common site for primary and metastatic bone tumors and therefore, it is a frequent site in which limb-sparing surgery is done. Between 1980 and 1998, the authors treated 110 consecutive patients who had distal femur resection and endoprosthetic reconstruction. There were 61 males and 49 females who ranged in age from 10 to 80 years. Diagnoses included 99 malignant tumors of bone, nine benign-aggressive lesions, and two nonneoplastic conditions that had caused massive bone loss and articular surface destruction. Reconstruction was done with 73 modular prostheses, 27 custom-made prostheses, and 10 expandable prostheses. Twenty-six gastrocnemius flaps were used for soft tissue reconstruction. All patients were followed up for a minimum of 2 years. Function was estimated to be good or excellent in 94 patients (85.4%), moderate in nine patients (8.2%), and poor in seven patients (6.4%). Complications included six deep wound infections (5.4%), six aseptic loosenings (5.4%), six prosthetic polyethylene component failures (5.4%), and local recurrence in five of 93 patients (5.4%) who had a primary bone sarcoma. The limb salvage rate was 96%. Distal femur endoprosthetic reconstruction is a safe and reliable technique of functional limb sparing that provides good function and local tumor control in most patients.     

Breast carcinoma metastatic to the bladder and renal pelvis requiring fulguration

Breast cancer metastatic to the bladder has rarely been reported in the literature. A patient presented to our institution with pathologically confirmed breast cancer metastatic to the bladder with renal pelvis involvement as seen on retrograde pyelography. We believe cystoscopy with biopsy and fulguration to be the treatment of choice for breast cancer that has metastasized to the bladder because of the low rate of survival in patients with hematuria related to metastatic breast cancer.