Dominant versus recessive traits conveyed by allelic mutations – to what extent is nonsense-mediated decay involved?

Mutations in ROR2 , encoding a receptor tyrosine kinase, can cause autosomal recessive Robinow syndrome (RRS), a severe skeletal dysplasia with limb shortening, brachydactyly, and a dysmorphic facial appearance. Other mutations in ROR2 result in the autosomal dominant disease, brachydactyly type B (BDB1). No functional mechanisms have been delineated to effectively explain the association between mutations and different modes of inheritance causing different phenotypes. BDB1-causing mutations in ROR2 result from heterozygous premature termination codons (PTCs) in downstream exons and the conveyed phenotype segregates as an autosomal dominant trait, whereas heterozygous missense mutations and PTCs in upstream exons result in carrier status for RRS. Given that the distribution of PTC mutations revealed a correlation between the phenotype and the mode of inheritance conveyed, we investigated the potential role for the nonsense-mediated decay (NMD) pathway in the abrogation of possible aberrant effects of selected mutant alleles. Our experiments show that triggering or escaping NMD may cause different phenotypes with a distinct mode of inheritance. We generalize these findings to other disease-associated genes by examining PTC mutation distribution correlation with conveyed phenotype and inheritance patterns. Indeed, NMD may explain distinct phenotypes and different inheritance patterns conveyed by allelic truncating mutations enabling better genotype–phenotype correlations in several other disorders.     

Decoherence of photon entanglement by transmission through brain tissue with Alzheimer’s disease

The generation, manipulation and quantification of non-classical light, such as quantum-entangled photon pairs, differs significantly from methods with classical light. Thus, quantum measures could be harnessed to give new information about the interaction of light with matter. In this study we investigate if quantum entanglement can be used to diagnose disease. In particular, we test whether brain tissue from subjects suffering from Alzheimer’s disease can be distinguished from healthy tissue. We find that this is indeed the case. Polarization-entangled photons traveling through brain tissue lose their entanglement via a decohering scattering interaction that gradually renders the light in a maximally mixed state. We found that in thin tissue samples (between 120 and 600 micrometers) photons decohere to a distinguishable lesser degree in samples with Alzheimer’s disease than in healthy-control ones. Thus, it seems feasible that quantum measures of entangled photons could be used as a means to identify brain samples with the neurodegenerative disease.     

In vitro comparison of endplate preparation between four mini-open interbody fusion approaches

Purpose

Discectomy and endplate preparation are important steps in interbody fusion for ensuring sufficient arthrodesis. While modern less-invasive approaches for lumbar interbody fusion have gained in popularity, concerns exist regarding their ability to allow for adequate disc space and endplate preparation. Thus, the purpose of this study was to quantitatively and qualitatively evaluate and compare disc space and endplate preparation achieved with four less-invasive approaches for lumbar interbody fusion in cadaveric spines.

Methods

A total of 24 disc spaces (48 endplates) from L2 to L5 were prepared in eight cadaveric torsos using mini-open anterior lumbar interbody fusion (mini-ALIF), minimally invasive posterior lumbar interbody fusion (MAS PLIF), minimally invasive transforaminal lumbar interbody fusion (MAS TLIF) or minimally invasive lateral, transpsoas interbody fusion (XLIF) on two specimens each, for a total of six levels and 12 endplates prepared per procedure type. Following complete discectomy and endplate preparation, spines were excised and split axially at the interbody disc spaces. Endplates were digitally photographed and evaluated using image analysis software. Area of endplate preparation was measured and qualitative evaluation was also performed to grade the quality of preparation.

Results

The XLIF approach resulted in the greatest relative area of endplate preparation (58.3 %) while mini-ALIF resulted in the lowest at 35.0 %. Overall, there were no differences in percentage of preparation between cranial and caudal endplates, though this was significantly different in the XLIF group (65 vs 52 %, respectively). ALL damage was observed in 3 MAS TLIF levels. Percentage of endplate that was deemed to have complete disc removal was highest in XLIF group with 90 % compared to 65 % in MAS TLIF group, 43 % in MAS PLIF, and 40 % in mini-ALIF group. Endplate damage area was highest in the MAS TLIF group at 48 % and lowest in XLIF group at 4 %.

Conclusions

These results demonstrate that adequate endplate preparation for interbody fusion can be achieved utilizing various minimally invasive approach techniques (mini-ALIF, MAS TLIF, MAS PLIF, XLIF), however, XLIF appears to provide a greater area of and more complete endplate preparation.

     

Substantial clinical benefit of minimally invasive lateral interbody fusion for degenerative spondylolisthesis

Purpose

Conventional lumbar arthrodesis for the treatment of degenerative spondylolisthesis (DS) is associated with high complication rates and variable clinical efficacy. Modern minimally invasive (MIS) approaches may reduce the morbidity and produce greater clinical improvement compared to traditional surgical techniques. The objective of this study is to report radiographic outcomes and evaluate clinical improvements in the context of substantial clinical benefit for DS patients treated with a MIS 90° lateral, transpsoas approach for lumbar interbody fusion.

Methods

From 2005 to 2011, 60 consecutive patients were treated with MIS lateral interbody fusion for Grade I or II DS at a single institution. Mean patient age was 68 years, 75 % were female, and 30 % had undergone previous lumbar surgery. A total of 71 levels were treated, supplemental posterior fixation was used in 57 (95 %) cases, and 26 (43 %) patients underwent additional direct posterior decompression.

Results

Average follow-up was 20.3 months. Average ORT, EBL, and LOS were 206 min, 83 cc, and 1.29 days, respectively. Complications occurred in 3 (5 %) patients. Transient approach-related thigh/groin pain was observed in 5 (8 %) cases. There were no cases of pseudoarthrosis. At 1 year, LBP improved 71 %, LP improved 68 %, ODI decreased 52 %, and SF-36 PCS and MCS improved 43 and 21 %, respectively. Substantial clinical benefit was met by 94.7 % of patients on NRS LBP, by 84.6 % on NRS LP, by 83.7 % on ODI, and by 66.7 % on SF-36 PCS. Disc height increased 71 % and segmental lordosis increased 27.8 % at treated levels. Foraminal height, width, and volume increased 19.7, 18.0, and 39.6 %, respectively. Slip improved 60.7 % with interbody fusion only and further improved to 69.2 % after the placement of supplemental instrumentation.

Conclusions

MIS lateral interbody fusion in the treatment of DS resulted in significant improvements in clinical and radiographic outcomes, with a low complication rate and a high proportion of patients achieving substantial clinical benefit.

     

Intraurethral tramadol alleviates rigid cystoscopy‐related pain in men

Considering the effectiveness of tramadol in alleviating pain following major operations, trauma, labour and even chronic neuropathic pain, this study was designed to evaluate the efficacy of intraurethral administration of the drug in alleviating cystoscopy‐related pain in men. Sixty male candidates of diagnostic cystoscopy, aged between 20 and 50 years, in ASA physical status I or II were included in the study. Patients were randomized into intervention [who received tramadol (100 mg) and lidocaine gel] or control group (in whom distilled water and lidocaine was administered) based on a permuted block randomization method. The severity of pain and the incidence of adverse effects were measured during and following the cystoscopy. The urologist' satisfaction was also assessed. Total pain score in the intervention group was significantly lower than the control group (P = 0·037). The urologist was more satisfied with the ease and convenience of performing the cystoscopy in the intervention group. No significant side effect was reported in either group. Adding 100 mg tramadol to lidocaine gel is more effective than using lidocaine gel alone in alleviating the pain associating with male rigid cystoscopy.     

Alcohol dehydrogenase polymorphism and Parkinson's disease

A particular alcohol dehydrogenase (ADH) polymorphism (allele A1) in the promoter region of the gene has been recently demonstrated to be associated with increased risk of Parkinson's disease (PD). In a case control study, we examine frequencies of ADH A1 allele in 100 PD patients (i.e. 200 alleles), 100 diseased controls (i.e. 200 alleles), and 194 healthy controls (i.e. 388 alleles). In addition, we study possible association of a combined non-amyloid component of plaque (NACP-Rep 1) allele and ADH A1 allele with risk of PD. There was no statistical significance of the frequencies of ADH A1 allele between PD patients 12/200 (6%), diseased controls 13/200 (6.5%), and healthy controls 20/388 (5.2%). No strong evidence of an association was found between ADH A1 allele and PD susceptibility in our study patients. There was also no suggestion of linkage disequilibrium between NACP-Rep 1 and ADH A1 alleles.     

The testicular protective effects of standardised hydroalcoholic extract of Ziziphus jujuba Mill against adriamycin-induced toxicity

In this study, because of the anti-inflammatory and antioxidant effect of the Ziziphus jujuba (ZJ), we assessed the protective properties of the ZJ extract against testis toxicity caused by Adriamycin in the rat. Twenty rats were grouped into (a) control, (b) Adriamycin, (c) ZJ group and (d) treatment group in which Adriamycin was administrated and the ZJ hydroalcoholic extract was used for three weeks. On the 21st day, two testes were removed to determine the oxidation markers and pathological evaluation. The levels of sex hormones were determined. Epididymis also was crushed, and its spermatozoa were evaluated as concentration, motility and normality. Adriamycin increased oxidative stress markers as well as Luteinising hormone, and follicle-stimulating hormone and decreased testosterone levels compared to control. In the treated group, the levels of the above markers improved. The decreased number and motility of spermatozoa in treatment group increased, and the increased rate of abnormal spermatozoa in this group decreased. Pathological evaluations also show the healing process of damaged testicular tissue in the group receiving the ZJ extract. The ZJ extract relatively improves oxidative stress, sperm characteristics, hormonal alternation and pathological changes. These findings reveal the probable role of ZJ effective compounds in repairing tissue damage.     

Malposition of central venous catheter in the left internal jugular vein--a case report

Malposition of central venous catheter is a complication of central venous catheterization. A case of left internal jugular catheterization via left external jugular vein is reported. Details of the procedure are described and the literature is reviewed for similar malpositions.