Secondary sphincter repair for anal incontinence following obstetric sphincter injury: functional outcome and quality of life at 18 years of follow-up.

AIM: Secondary sphincter repair has been the conventional management of anal incontinence (AI) when a structural defect in the sphincter is recognized. However, disappointing long-term results have contributed to a tendency towards an increasing use of alternative treatment methods. This study aimed to assess the long-term functional outcomes following a secondary sphincter repair in women with AI after obstetric sphincter injury. METHOD: This is a questionnaire study of women who underwent a secondary sphincter repair in Denmark between January 1990 and December 2005. Patients were identified through the Danish National Patient Registry. Functional outcomes were assessed by a self-administered questionnaire in 2010 and 2018. Primary outcomes were Wexner and St. Mark's scores. Impact on quality of life was assessed using the Fecal Incontinence Quality of Life Scale. RESULTS: Functional outcome was assessed in 370 women in 2010 and 255 women in 2018. At 18.3 [interquartile range (IQR 15.0-22.0)] years of follow-up, the mean ± SD Wexner score was 8.8 ± 4.8 and the mean St. Mark's score was 11.7 ± 5.0. Flatus incontinence was the most frequent symptom, reported by 97%. Incontinence for liquid and solid stools was reported by 75% and 54%, respectively. There were no significant changes in incontinence frequencies over time. Women with a Wexner score of ≥ 9 had a significantly lower quality of life score in all domains than did women with a Wexner score of < 9 (P < 0.001). CONCLUSION: At long-term follow-up, few patients are fully continent following a secondary sphincter repair. However, it appears that the functional results remain stable at very long-term follow-up.

Epigenome-wide association study of depression symptomatology in elderly monozygotic twins.

Depression is a severe and debilitating mental disorder diagnosed by evaluation of affective, cognitive and physical depression symptoms. Severity of these symptoms strongly impacts individual's quality of life and is influenced by a combination of genetic and environmental factors. One of the molecular mechanisms allowing for an interplay between these factors is DNA methylation, an epigenetic modification playing a pivotal role in regulation of brain functioning across lifespan. The aim of this study was to investigate if there are DNA methylation signatures associated with depression symptomatology in order to identify molecular mechanisms contributing to pathophysiology of depression. We performed an epigenome-wide association study (EWAS) of continuous depression symptomatology score measured in a cohort of 724 monozygotic Danish twins (346 males, 378 females). Through EWAS analyses adjusted for sex, age, flow-cytometry based blood cell composition, and twin relatedness structure in the data we identified depression symptomatology score to be associated with blood DNA methylation levels in promoter regions of neuropsin (KLK8, p-value = 4.7 × 10-7) and DAZ associated protein 2 (DAZAP2, p-value = 3.13 × 10-8) genes. Other top associated probes were located in gene bodies of MAD1L1 (p-value = 5.16 × 10-6), SLC29A2 (p-value = 6.15 × 10-6) and AKT1 (p-value = 4.47 × 10-6), all genes associated before with development of depression. Additionally, the following three measures (a) DNAmAge (calculated with Horvath and Hannum epigenetic clock estimators) adjusted for chronological age, (b) difference between DNAmAge and chronological age, and (c) DNAmAge acceleration were not associated with depression symptomatology score in our cohort. In conclusion, our data suggests that depression symptomatology score is associated with DNA methylation levels of genes implicated in response to stress, depressive-like behaviors, and recurrent depression in patients, but not with global DNA methylation changes across the genome.

Long-term function and morphology of the anal sphincters and the pelvic floor after primary repair of obstetric anal sphincter injury.

AIM: More than 50% of women experience deteriorating continence over time following primary repair of obstetric anal sphincter injuries. The objectives of this study were to assess the function and morphology of the anal sphincters and pelvic floor in women with long-term faecal incontinence after sphincter repair (primary end-point) and to evaluate their correlation with severity of incontinence (secondary end-point). METHOD: The participants in this prospective study were recruited from a cohort of all women who sustained third or fourth degree obstetric sphincter injury reconstruction (cases) from January 1976 to November 1991. The women who delivered immediately before and after each case, without sustaining obstetric damage, were included as controls. Cases and controls were stratified into three categories: (i) continent; (ii) minor incontinence; and (iii) severe incontinence. The function and morphology of the anal sphincters and pelvic floor were evaluated by MRI, three-dimensional endoanal ultrasonography and anorectal physiology tests. RESULTS: Fifty-nine women (29 cases/30 controls; mean age 51/53 years; mean follow-up 23.7/24.1 years, respectively) were assessed. Morphologically, cases had a significantly shorter anterior external anal sphincter length compared with controls when evaluated by three-dimensional endoanal ultrasonography (8.6 vs 10.2 mm; P = 0.03). Functionally, cases with severe incontinence had a significantly shorter anterior sphincter length compared with cases with minor incontinence (7.7 vs 10.4 mm; P = 0.04). No correlation could be found between anal pressures and severity of incontinence in the case group. CONCLUSIONS: Cases had a significantly shorter anterior external anal sphincter length. Functionally, anterior sphincter length correlated with increased severity of incontinence.

Contribution of genetic polymorphisms on functional status at very old age: a gene-based analysis of 38 genes (311 SNPs) in the oxidative stress pathway.

Preservation of functional ability is a well-recognized marker of longevity. At a molecular level, a major determinant of the physiological decline occurring with aging is the imbalance between production and accumulation of oxidative damage to macromolecules, together with a decreased efficiency of stress response to avoid or repair such damage. In this paper we investigated the association of 38 genes (311 SNPs) belonging to the pro-antioxidant pathways with physical and cognitive performances, by analyzing single SNP and gene-based associations with Hand Grip strength (HG), Activities of Daily Living (ADL), Walking Speed (WS), Mini Mental State Examination (MMSE) and Composite Cognitive Score (CCS) in a Cohort of 1089 Danish nonagenarians. Moreover, for each gene analyzed in the pro-antioxidant pathway, we tested the influence on longitudinal survival. In the whole sample, nominal associations were found for TXNRD1 variability with ADL and WS, NDUFS1 and UCP3 with HG and WS, GCLC and UCP2 with WS (p<0.05). Stronger associations although not holding the multiple comparison correction, were observed between MMSE and NDUFV1, MT1A and GSTP1 variability (p<0.009). Moreover, we found that association between genetic variability in the pro-antioxidant pathway and functional status at old age is influenced by sex. In particular, most significant associations were observed in nonagenarian females, between HG scores and GLRX and UCP3 variability, between ADL levels and TXNRD1, MMSE and MT1A genetic variability. In males, a borderline statistically significant association with ADL level was found for UQCRFS1 gene. Nominally significant associations in relation to survival were found in the female sample only with SOD2, NDUFS1, UCP3 and TXNRD1 variability, the latter two confirming previous observations reported in the same cohort. Overall, our work supports the evidence that genes belonging to the pro-anti-oxidant pathway are able to modulate physical and cognitive performance after the ninth decade of life, finally influencing extreme survival.

Radial sine-Gordon kinks as sources of fast breathers.

We consider radial sine-Gordon kinks in two, three, and higher dimensions. A full two-dimensional simulation showing that azimuthal perturbations remain small allows us to reduce the problem to the one-dimensional radial sine-Gordon equation. We solve this equation on an interval [r(0),r(1)] and absorb all outgoing radiation. As the kink shrinks toward r(0), before the collision, its motion is well described by a simple law derived from the conservation of energy. In two dimensions for r(0)≤2, the collision disintegrates the kink into a fast breather, while for r(0)≥4 we obtain a kink-breather metastable state where breathers are shed at each kink "return." In three and higher dimensions d, an additional kink-oscillon state appears for small r(0). On the application side, the kink disintegration opens the way for new types of terahertz microwave generators.

Information on plant foods in eBASIS: what is in a correct botanical scientific name?

This paper presents the plant information included in the eBASIS (BioActive Substances in Foods Information System) database on composition and biological activity of selected bioactive compounds from European plant/mushroom foods with putative beneficial and/or toxic effects. The European Food Information Resource (EuroFIR)-NETTOX Plant List (2007) presents scientific and vernacular names in 15 European languages for around 325 major European plant/mushroom foods and also for different parts of these foods. This list and its predecessor, the NETTOX List of Food Plants, have been used by national food authorities and within the European Union for consideration of plants and mushrooms that have been used to a significant degree up to 1997 and are therefore not covered by the novel food regulation (European Parliament and Council of the European Union, 1997). The species and the plant part studied are insufficiently characterised in many scientific papers. This paper informs about the naming of plants and mushrooms as an aid for scientists who are not botanists or mycologists themselves. Knowledge on scientific names used, including synonyms, may also be important for finding all relevant papers when searching the literature. In many cases, vernacular/trivial names in, for example, English do not uniquely identify the species. Finally, recommendations are given to assist researchers and reviewers of papers dealing with botanical/mycological information.

Intersphincteric injected silicone biomaterial implants: a treatment for faecal incontinence.

INTRODUCTION: The aim of this study was to evaluate the functional efficacy of intersphincteric injected silicone biomaterial (PTQ) in patients with faecal incontinence. METHOD: Prospective study of 33 consecutively included patients (male-female ratio: 9:24); median age 53 years (range: 21-75 years) with faecal incontinence of varied aetiology. The PTQ was injected under general anaesthesia with antibiotic cover. All patients had anorectal manometry, endoanal ultrasonography and responded to faecal incontinence severity questionnaire (Wexner score) and SF-36 short-form health survey questionnaire before and 3 months postoperatively. At time of final follow-up, the continence status and quality of life questionnaire were reassessed. RESULTS: The mean follow-up was 12.9 months (range: 3-22 months). The Wexner Continence Score was significantly reduced short term from 12.7 to 11.0 (P = 0.03) and long term to 10.4 (P = 0.02). The long-term effect on liquid stool incontinence continued to improve significantly (P < 0.01). Six patients (18%) reported major improvement in Wexner Continence Score at the time of final follow-up. Anorectal manometry was not affected except for the maximum tolerable rectal volume, which was significantly reduced (P < 0.05). The SF-36 short-form questionnaire showed no significant improvement in quality of life after treatment with PTQ. CONCLUSIONS: Treatment with intersphincteric injection of PTQ implants can provide an improvement in anal continence in patients with faecal incontinence of varied aetiology. However, the improvement is mainly limited to soiling and minor leakage. A majority of patients still have severe incontinence, both short- and long-term.

Impact of vector-priming on the immunogenicity of a live recombinant Salmonella enterica serovar typhi Ty21a vaccine expressing urease A and B from Helicobacter pylori in human volunteers.

Orally administered recombinant Salmonella vaccines represent an attractive option for mass vaccination programmes against various infectious diseases. Therefore, it is crucial to gather knowledge about the possible impact of preexisiting immunity to carrier antigens on the immunogenicity of recombinant vaccines. Thirteen volunteers were preimmunized with Salmonella typhi Ty21a in order to evaluate the effects of prior immunization with the carrier strain. Then, they received three doses of 1-2 x 10(10) viable organisms of either the vaccine strain S. typhi Ty21a (pDB1) expressing subunits A and B of recombinant Helicobacter pylori urease (n = 9), or placebo strain S. typhi Ty21a (n = 4). Four volunteers were preimmunized and boosted with the vaccine strain S. typhi Ty21a (pDB1). No serious adverse effects were observed in any of the volunteers. Whereas none of the volunteers primed and boosted with the vaccine strain responded to the recombinant antigen, five of the nine volunteers preimmunized with the carrier strain showed cellular immune responses to H. pylori urease (56%). This supports the results of a previous study in non-preimmunized volunteers where 56% (five of nine) of the volunteers showed a cellular immune response to urease after immunisation with S. typhi Ty21a (pDB1).

The use of the laser in the treatment of arterio-venous malformations and vascular tumours of the liver.

Vascular tumours of the liver present variously in the paediatric age group. Their clinical course depends on tumour size, its growth characteristics, localization and complications. The most feared complications are cardiac failure and the Kasabach-Merritt syndrome which may occur in up to 50% of affected children. In haemangioendotheliomata and capillary haemangiomata spontaneous regression can be expected. Regression may be stimulated by x-ray radiation therapy, corticosteroids, Endoxane or alpha Interferon. Emergency percutaneous catheter embolization or operation must be carried out in the event of such complications. The Nd:YAG laser is particularly well suited for these cases. In all events, careful interdisciplinary cooperation among paediatricians, radiologists, cardiologists, oncologists and paediatric surgeons is required owing to threatening complications which mostly occur in neonates and infants.