RUNX2 as a Prognostic Factor in Human Cancers.

The RUNX2 transcription factor was discovered as an essential transcriptional regulator for commitment to osteoblast lineage cells and bone formation. Expression of RUNX2 in other tissues, such as breast, prostate, and lung, has been linked to oncogenesis, cancer progression, and metastasis. In this study, we sought to determine the extent of RUNX2 involvement in other tumors using a pan-cancer analysis strategy. We correlated RUNX2 expression and clinical-pathological parameters in human cancers by interrogating publicly available multiparameter clinical data. Our analysis demonstrated that altered RUNX2 expression or function is associated with several cancer types from different tissues. We identified three tumor types associated with increased RUNX2 expression and four other tumor types associated with decreased RUNX2 expression. Our pan-cancer analysis for RUNX2 revealed numerous other discoveries for RUNX2 regulation of different cancers identified in each of the pan-cancer databases. Both up and down regulation of RUNX2 was observed during progression of specific types of cancers in promoting the distinct types of cancers.

Martian subsurface cryosalt expansion and collapse as trigger for landslides.

On Mars, seasonal martian flow features known as recurring slope lineae (RSL) are prevalent on sun-facing slopes and are associated with salts. On Earth, subsurface interactions of gypsum with chlorides and oxychlorine salts wreak havoc: instigating sinkholes, cave collapse, debris flows, and upheave. Here, we illustrate (i) the disruptive potential of sulfate-chloride reactions in laboratory soil crust experiments, (ii) the formation of thin films of mixed ice-liquid water "slush" at -40° to -20°C on salty Mars analog grains, (iii) how mixtures of sulfates and chlorine salts affect their solubilities in low-temperature environments, and (iv) how these salt brines could be contributing to RSL formation on Mars. Our results demonstrate that interactions of sulfates and chlorine salts in fine-grained soils on Mars could absorb water, expand, deliquesce, cause subsidence, form crusts, disrupt surfaces, and ultimately produce landslides after dust loading on these unstable surfaces.

The Physician's Duty to Warn Their Patients About the Risks Associated with Medical Intervention: A Review and Discussion.

Since the landmark case of Montgomery v Lanarkshire in 20151, much has been written in medical press regarding the implications for medical practice. The moral duty - varied though it has been over this time, has been discussed since the earliest days of the medical profession. The law has sought to define this duty in response to changes in society, and the nature of the relationship between doctor and patient. The moral and legal duty are intrinsically linked, but the latter must surely follow the former for "the law has little to do with morally required forms of communication in the clinic and in the research environment."2 The common law nature of this process has resulted in an inconsistent and often tortuous path as societal standards have shifted. Accordingly, the ultimate definition of the legal doctrine, "informed consent," has changed since its relatively recent entry into the medicolegal vocabulary. These parallel shifts in the legal and moral duty to disclose risk have resulted in a confusing melee of evidence and recommendations for clinicians. We address the development of the law of "informed consent," as the legal mirror of the moral duty upon a clinician to disclose risk to their patient.

Cochlear implantation in keratitis-ichthyosis-deafness syndrome: 10-year follow-up of two patients.

OBJECTIVE AND IMPORTANCE: The objective of this study was to describe long-term outcomes after cochlear implantation in keratitis-ichthyosis-deafness (KID) syndrome, often caused by GJB2 mutations, in the context of other reported cases. Clinical presentation and intervention: The authors conducted correlative clinical and molecular genetic analysis on two implanted patients with KID syndrome, and tabulated their clinical outcomes. Both children had initially successful surgery. In one case, due to skin-related problems, despite extensive salvage surgery cochlear explantation was required. This patient now communicates with sign language and lip-reading. This contrasts with the outcome for the other patient whereby at post-operative year 10 he is able to easily converse by telephone. Both patients each carry a de novo 148G > A GJB2 mutation. CONCLUSION: Patients with KID syndrome appear to be good candidates for cochlear implantation but may face significant skin-related problems which could disrupt successful post-operative habilitation. Consultation with dermatological colleagues regarding any new therapies may be warranted.

Cochlear Implantation in Brown-Vialetto-Van-Laere syndrome.

OBJECTIVE: To report outcomes for the first known cochlear implantation procedures in two patients with Brown-Vialetto-Van-Laere syndrome. PATIENTS: Two adult patients (a brother and sister) with post-lingual sensorineural deafness associated with Brown-Vialetto-Van-Laere syndrome. The female patient presented with a milder form of the syndrome. INTERVENTION: Cochlear implantation. MAIN OUTCOME MEASURE: Post-implantation speech discrimination scores. RESULTS: Auditory evoked potential testing suggested pathological changes in both patients' cochleae, auditory nerves, brainstem and (probably) central auditory pathways. In the male patient, despite implantation of the better ear, the Bamford-Kowal-Bench sentence score was zero at 21 months post-implantation. In the female patient, Bamford-Kowal-Bench sentence scores at six months post-implantation were 25 per cent in quiet and 3 per cent in noise. CONCLUSION: These poor clinical outcomes appear to be related to retrocochlear and probable central auditory pathway degeneration.

Treatment of a cochlear implant biofilm infection: a potential role for alternative antimicrobial agents.

OBJECTIVE: This study aimed to investigate antimicrobial treatment of an infected cochlear implant, undertaken in an attempt to salvage the infected device. METHODS: We used the broth microdilution method to assess the susceptibility of meticillin-sensitive Staphylococcus aureus isolate, cultured from an infected cochlear implant, to common antimicrobial agents as well as to novel agents such as tea tree oil. To better simulate in vivo conditions, where bacteria grow as microcolonies encased in glycocalyx, the bactericidal activity of selected antimicrobial agents against the isolate growing in biofilm were also compared. RESULTS: When grown planktonically, the S aureus isolate was susceptible to 17 of the 18 antimicrobials tested. However, when grown in biofilm, it was resistant to all conventional antimicrobials. In contrast, 5 per cent tea tree oil completely eradicated the biofilm following exposure for 1 hour. CONCLUSION: Treatment of infected cochlear implants with novel agents such as tea tree oil could significantly improve salvage outcome.

Auditory sensory memory and working memory processes in children with normal hearing and cochlear implants.

There can be wide variation in the level of oral/aural language ability that prelingually hearing-impaired children develop after cochlear implantation. Automatic perceptual processing mechanisms have come under increasing scrutiny in attempts to explain this variation. Using mismatch negativity methods, this study explored associations between auditory sensory memory mechanisms and verbal working memory function in children with cochlear implants and a group of hearing controls of similar age. Whilst clear relationships were observed in the hearing children between mismatch activation and working memory measures, this association appeared to be disrupted in the implant children. These findings would fit with the proposal that early auditory deprivation and a degraded auditory signal can cause changes in the processes underpinning the development of oral/aural language skills in prelingually hearing-impaired children with cochlear implants and thus alter their developmental trajectory.

Self-reported benefits from successive bilateral cochlear implantation in post-lingually deafened adults: randomised controlled trial.

Adult users of unilateral Nucleus CI24 cochlear implants with the SPEAK processing strategy were randomised either to receive a second identical implant in the contralateral ear immediately, or to wait 12 months while they acted as controls for late-emerging benefits of the first implant. Twenty four subjects, twelve from each group, completed the study. Receipt of a second implant led to improvements in self-reported abilities in spatial hearing, quality of hearing, and hearing for speech, but to generally non-significant changes in measures of quality of life. Multivariate analyses showed that positive changes in quality of life were associated with improvements in hearing, but were offset by negative changes associated with worsening tinnitus. Even in a best-case scenario, in which no worsening of tinnitus was assumed to occur, the gain in quality of life was too small to achieve an acceptable cost-effectiveness ratio. The most promising strategies for improving the cost-effectiveness of bilateral implantation are to increase effectiveness through enhanced signal processing in binaural processors, and to reduce the cost of implant hardware.

Ovarian reserve, female age and the chance for successful pregnancy.

Both quantitative and qualitative factors regarding egg production are strong influences on IVF outcome. Markers of ovarian reserve such as basal FSH, clomiphene citrate challenge test (CCCT), and antral follicle counts are good predictors of the quantity of eggs which can be induced to grow. However, the quality of those eggs seems better predicted by the age of the women. In women past age 40, current success rates are low overall, even in those who good ovarian reserve who make many eggs; at this age, quantity does not make up for quality. By contrast, young women with limited ovarian reserve can have good success rates despite their limited cohort of eggs, because the eggs themselves are of high potential; here quality matters more than quantity. The ramifications of these observations include the following: diminished ovarian reserve should not be used as an exclusionary criterion in young women, because overall they still have satisfactory pregnancy rates, though their risk of cancellation is increased. In women past age 40, normal ovarian reserve testing is not reassuring because even reduced egg quality is likely to limit the opportunity for successful pregnancy no matter how many eggs are available.

A review of cochlear implantation in mitochondrial sensorineural hearing loss.

OBJECTIVE: Mitochondrial sensorineural hearing loss (SNHL) may be nonsyndromic (occurring in isolation), associated with the A1555G mutation in the MTRNR1 gene. Mitochondrial SNHL may also be syndromic, associated with the A3243G point mutation in the MTTL1 gene. In syndromic cases-mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS), maternally inherited diabetes and deafness, Kearns-Sayre syndrome, and chronic progressive external ophthalmoplegia-the SNHL compounds already existing disabilities. The genetic basis for mitochondrial SNHL and postulated sites of pathologic changes are discussed. DATA SOURCES: Sources used were relevant clinical and basic science publications. STUDY SELECTION: A search of the entire databases of Medline and Web of Science, using various subject headings and free-text terms, was used to identify patients with mitochondrial disease having cochlear implants. DATA EXTRACTION: The data from publications were critically reviewed and tabulated to assess implantation outcomes. DATA SYNTHESIS: The data were not amenable to formal meta-analysis or valid data summarization, other than descriptive statistics. CONCLUSIONS: There is an increasing awareness of the prevalence of mitochondrial SNHL and its progressive nature. High-risk candidates warrant genetic testing and family screening. Correlating the data for mitochondrial SNHL as a treatable entity is important, and the authors present an overview of these patients successfully rehabilitated by cochlear implantation.

Management of otoscierosis--an Irish perspective.

The last 30 years have seen a gradual change in the management of otosclerosis. The aim of this study is to evaluate the current practice amongst Irish otolaryngology consultants by a questionnaire and to compare it with the practice currently followed in Great Britain. Thirty-eight responses (67.9%) were available for analysis. The overall trend is towards centralisation with a reduction in the number of surgeons undertaking stapes surgery (39%). The majority of consultants (67%) who undertake stapes surgery would operate for a unilateral conductive loss and 67% would undertake bilateral stapes surgery. Stapedotomy is the only operation performed (100%) with none of the consultants performing partial or total stapedectomies.

Cochlear implantation in maternal inherited diabetes and deafness syndrome.

We describe a rare case of a gradually progressive hearing loss in a patient with maternally inherited diabetes and deafness (MIDD) syndrome successfully rehabilitated with a cochlear implant. The possible aetiology of the hearing loss in these cases is discussed.

Cochlear implantation in the obliterated cochlea.

We present three cases of acquired deafness, associated with obliterated cochleas, in which the apparently radiologically more favourable side was chosen for implantation. In the first case, because of unexpected obliteration, only a partial insertion was possible. Deteriorating performance and non-auditory stimulation of the facial nerve led to removal of the implant and a contralateral implantation with full insertion under the same anaesthetic gave a good postoperative result. In the second case, CT scanning indicated minimal obliteration, but extensive obliteration was encountered at surgery, which required double-array insertion with a delayed but satisfactory outcome. In the third case, extensive unexpected obliteration was noted at surgery and, in light of the experience gained with the first two cases, it was decided not to proceed but to explore the contralateral side. At surgery on the contralateral side, a patent cochlea was noted with full electrode insertion and an excellent outcome. These cases demonstrate a learning curve for this department and our philosophy now is to explore the contralateral ear rather than accept a partial insertion.

Management of otosclerosis in the UK.

The last 30 years has seen a gradual change in the management of otosclerosis. The aim of this study is to evaluate the current practice among British otolaryngology consultants using a questionnaire, and to compare it with the practice reported in a survey 8 years ago. A total of 353 valid responses (64.5%) were available for analysis. The overall trend is towards centralization, with a reduction in the number of surgeons undertaking stapes surgery (49.9%). The majority of consultants (81.3%) who undertake stapes surgery would operate for a unilateral conductive loss and 75.1% would undertake bilateral stapes surgery. Stapedotomy is the operation of choice (82%), with a few consultants performing partial or rarely total stapedectomies. Postoperative restrictions and follow-up times vary widely amongst surgeons, with the senior surgeons tending to be more conservative than the younger consultants.

Bipolar scissors versus cold dissection for pediatric tonsillectomy--a prospective, randomized pilot study.

OBJECTIVE: To evaluate bipolar scissors tonsillectomy by comparing it with traditional cold dissection tonsillectomy. The outcome measures used were: (1) intra-operative bleeding; (2) operative time; (3) post-operative pain; and (4) complication rates including reactionary and secondary hemorrhage. METHOD: A prospective, randomized multiunit study involving three teaching hospitals in Belfast. Fifty consecutive children aged 10-16 years undergoing tonsillectomy for recurrent or chronic tonsillitis, between March 2000 and September 2000 were recruited as a subgroup of 200 patients selected for this study. These children were analysed separately from the adults, in a pilot study for the above parameters. RESULTS: The mean age of the study population was 14.3 years. Sixty-eight percent of the children were girls. Median intra-operative blood loss was 6 ml for bipolar scissors tonsillectomy and 86 ml for cold dissection tonsillectomy (P<0.001). The median operative time was 10.5 min for bipolar scissors tonsillectomy compared to 14.5 min for the cold dissection method (P=0.001). There was no statistically significant difference in the pain scores between the two methods (P>0.05). The overall reactionary hemorrhage rate was 4% while the overall secondary hemorrhage rate was 14%. The hospital readmission rate was 4%. The reactionary and secondary hemorrhage rates were unaffected by the surgical method. CONCLUSIONS: This pilot study has shown that bipolar scissors tonsillectomy is a relatively safe technique in children aged 10-16 years with a similar morbidity to the cold dissection method. Its use is associated with a significant decrease in surgical time and blood loss compared to the cold dissection method. These advantages make it a favourable instrument for pediatric tonsillectomy especially in this age group.

Universality and scaling in the disordering of a smectic liquid crystal.

We present experimental and theoretical studies of the effects of quenched disorder on one-dimensional crystal ordering in three dimensions. This fragile smectic liquid crystal layering, the material with the simplest positional order, is also the most easily deformed periodic structure and is, therefore, profoundly affected by disorder, introduced here by confinement in silica aerogel. Theory and experiment combine to characterize this system to an extraordinary degree, their close accord producing a coherent picture: crystal ordering is lost, giving way to extended short-range correlations that exhibit universal structure and scaling, anomalous layer elasticity, and glassy dynamics.

Vaginal misoprostol enhances intrauterine insemination.

This study examined whether the prostaglandin E(1) analogue misoprostol (400 microgram), when placed vaginally at the time of intrauterine insemination (IUI) improves pregnancy rates. A prospective, placebo-controlled, randomized and double-blind study involving 274 women in 494 IUI cycles resulted in a total of 64 pregnancies (13% per cycle). Misoprostol cycles totalled 253, with 43 pregnancies (17% per cycle), whereas placebo cycles totalled 241, with 21 pregnancies (9% per cycle). The cumulative pregnancy rate with misoprostol treatment was significantly greater than with placebo (P = 0.004, Cox proportional hazards regression). The benefit of misoprostol was seen in clomiphene cycles (14 versus 4%, P = 0.006), and was indicated in FSH cycles (33 versus 15%, borderline significance) and natural cycles (15.6 versus 7.7%, not significant), but was not seen in clomiphene/FSH cycles (18.2 versus 23.5%, not significant). Misoprostol treatment did not increase pain score on the day of IUI (1.1 versus 1.4) and at 1 day post IUI (0.6 versus 0.8). Complications were rare in both groups [six (2%) subject cycles in the misoprostol cycles compared with two (1%) in the placebo group]. It is concluded that the use of vaginal misoprostol may improve the chance for pregnancy in women having IUI in a wide variety of cycle types.