Identification of a new locus for autosomal dominant non-syndromic hearing impairment (DFNA7) in a large Norwegian family

Hereditary hearing impairment affects about 1 in 1000 newborns. In most cases hearing loss is non-syndromic with no other clinical features, while in other families deafness is associated with specific clinical abnormalities. Analysis of large families with non-syndromic and syndromic deafness have been used to identify genes or gene locations that cause hearing impairment. The present report describes a large Norwegian family with autosomal dominant non-syndromic, progressive high tone hearing loss with linkage to 1q21-q23. A maximum LOD score of 7.65 (theta = 0.00) was obtained with the microsatellite marker D1S196. Analysis of recombinant individuals maps the deafness gene (DFNA7) to a 22 cM region between D1S104 and D1S466. The region contains several attractive candidate genes. This report supports the idea of extensive genetic heterogeneity in hereditary hearing impairment and represents the first localization of a deafness gene in a Norwegian family.      

The Current UK Consensus on the Management of Weber B and Posterior Ankle Fractures: A Questionnaire Study as Part of the Acute Management of Ankle Fractures (AUGMENT) Audit

Ankle fractures are common conditions which are associated with significant morbidity when managed incorrectly. With the incidence due to triple by 2030, standards of practice were created by the British Orthopaedic Association and the British Orthopaedic Foot and Ankle Society to ensure optimal treatment. In spite of this, anecdotally there is still a variation in practice and therefore a questionnaire study was designed to explore clinician decision-making around Weber B and Posterior Malleolus ankle fractures. Five scenarios explored management regarding minimally and grossly displaced injuries, as well as the use of further imaging. The questionnaires were distributed via AUGMENT collaborators at their sites and at the British Orthopaedic Foot and Ankle Society congress 2018. About 315 questionnaires were completed and included in analysis. For Weber B injuries, overall there was a consensus across all respondents with minimally displaced and grossly displaced fractures being treated conservatively and operatively respectively. For Posterior Malleolus injuries, there was variation in practice between Foot and Ankle specialists and their non-Foot and Ankle colleagues. Computed tomography (CT) was more likely to be used to assess these injuries by specialists (97.50 vs 69.79%) and these injuries were more likely to be treated operatively across the board. This study identified key variation in practice of the management of Posterior Malleolar ankle fractures, including the use of imaging to further define the anatomy and the decision to operate. Foot and Ankle surgeons were more likely to organize CT scans and to surgically manage these injures.     

Mononucleosis syndrome and coincidental human herpesvirus-7 and Epstein-Barr virus infection

Two girls (a 5 year old and a 21 month old) experiencing mononucleosis syndrome with coincidental human herpesvirus (HHV)-7 and Epstein-Barr virus (EBV) infections are described. One patient had primary HHV-7 infection and reactivated EBV infection. The other had primary HHV-7 and EBV infections. These cases indicated that HHV-7 is capable of inducing infectious mononucleosis-like illness. Multiple herpesvirus infection in one of the patients also suggests that interaction among herpesviruses can occur in vivo. The consequence of this interaction may have clinical implications.     

In vitro and in vivo antifungal activities of the eight steroid saponins from Tribulus terrestris L. with potent activity against fluconazole-resistant fungal pathogens

Antifungal activity of natural products is being studied widely. Saponins are known to be antifungal and antibacterial. We have isolated eight steroid saponins from Tribulus terrestris L. , namely TTS-8, TTS-9, TTS-10, TTS-11, TTS-12, TTS-13, TTS-14 and TTS-15. TTS-12 and TTS-15 were identified as tigogenin-3-O-β-D-xylopyranosyl（1→ 2）-[-β-D-xylopyranosyl（ 1 → 3 ） 3-β- D-glucopyranosyl （ 1 → 4 ）- 1- α-L-rhamnopyranosyl （ 1 → 2 ） 3-β-D-galactopyranoside and tigogenin-3-O-β-D-glucopyranpyranosyl（1→2）-[-β-D-xylopyranosyl（1→ 3）3-β-D-glucopyranosyl（1→4）-β-D-galactopyranoside, respectively. The in vitro antifungal activities of the eight saponins against six fluconazole-resistant yeasts, Candida albicans, Candida glabrata, Candida para psilosis , Candida tropicalis , Candida krusei , and Cryptococcus neo f ormans were studied using microbroth dilution assay. The results showed that TTS-12 and TTS-15 were very effective against several pathogenic candidal species and C. neoformans in vitro. It is noteworthy that TTS-12 and TTS-15 were very active against fluconazole-resistant C. albicans （MIC80 = 4.4, 9.4 mg/ml）, C. neoformans （MIC80 =10.7, 18.7 mg/ml） and inherently resistant C. krusei （MIC80 =8.8, 18.4 mg/ml）. So in vivo activity of TTS-12 in a vaginal infection model with fluconazole-resistant C. albicans was studied in particular. Our studies revealed TTS-12 also showed in vivo activities against fluconazole-resistant yeasts. In conclusion, steroid saponins TTS-12 and TTS-15 from Tribulus terrestris L. have significant in vitro antifungal activity against fluconazole-resistant fungi, especially TTS-12 also showed in vivo activity against fluconazole-resistant C. albicans.     

The dystrophin gene and cognitive function in the general population

The aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included in the analysis. To determine the association between DMD variants and cognitive ability, linear (mixed) modeling with adjustment for age, sex and education was used. Moreover, Sequence Kernel Association Test (SKAT) was used to test the overall association of the rare genetic variants present in the DMD with cognitive traits. Although no DMD variant surpassed the prespecified significance threshold (P<1 × 10⁻⁴), rs147546024:A>G showed strong association (β=1.786, P-value=2.56 × 10⁻⁴) with block-design test in the ERF study, while another variant rs1800273:G>A showed suggestive association (β=−0.465, P-value=0.002) with Mini-Mental State Examination test in the RS. Both variants are highly conserved, although rs147546024:A>G is an intronic variant, whereas rs1800273:G>A is a missense variant in the DMD which has a predicted damaging effect on the protein. Further gene-based analysis of DMD revealed suggestive association (P-values=0.087 and 0.074) with general cognitive ability in both cohorts. In conclusion, both single variant and gene-based analyses suggest the existence of variants in the DMD which may affect cognitive functioning in the general populations.     

Search for intrafamilial transmission of hepatitis C virus in hemophilia patients

This study was performed to determine the risk of family members of anti-hepatitis C virus (HCV)-positive hemophilia patients (index patients) for infection with HCV compared with the risk of acquiring hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis A virus (HAV) infection. All index patients (n = 141) were found to be positive by first and second generation anti-HCV enzyme immunoassays (EIAs). Among their household contacts (n = 228), 224 were negative and 1 positive by both assays. Three contacts gave positive results in first generation anti-HCV EIA and negative results in second generation assay. This latter result was confirmed by further tests (neutralization test, synthetic peptides, and supplemental assay). Percent positivity for anti-HBc was about the same in non-sexual household contacts and sexual partners (13 of 109 [12%] and 7 of 54 [13%], respectively). Percent prevalence of anti-HBc was higher in contacts of index patients with chronic hepatitis B than in those of index patients who had recovered from that disease (6 of 20 [30%] and 14 of 133 [10%], respectively; P < .05). The HBV infection rate of contacts participating in controlled self-treatment was not higher than that of controls (3 of 57 [5%] and 10 of 98 [10%], respectively). Of 44 sexual partners, 5 (11%) were found to be positive for anti-HIV. Prevalence of anti-HAV matched with the age-related distribution in the German population. These findings suggest that intrafamilial transmission of HCV to family members of hemophilia patients is uncommon. In contacts of hemophilia patients, the risk of acquiring HBV infection seems to be as high in household contacts as in sexual contacts. Participation in controlled self-treatment does not appear to be an additional risk for HCV and HBV infection. There is no doubt that sexual transmission of HCV is less common than that of HBV and HIV.     

Commentary: The doctor will not see you now – therapist‐light therapy for PTSD in children as the way ahead? Reflections on Salloum et al. (2016)

Salloum and colleagues have presented data in support of a novel and cost‐effective approach to the treatment of PTSD in young children. In this commentary, I outline an argument for why their stepped‐care model may be an important change to how psychological therapies for trauma‐exposed youth are delivered, and propose further caveats that need to be addressed in future research.