A short- and long-term follow-up study of intersphincteric NASHA Dx implants for fecal incontinence.

BACKGROUND: The bulking agent NASHA Dx injected into the submucosal layer is effective in the treatment of fecal incontinence (FI) at short-and medium-term follow-up but efficacy after injection in the intersphincteric location is unknown. The aim of this study was to determine the short- and long-term efficacy and safety of NASHA Dx injected into the intersphincteric location for FI. METHODS: Patients were recruited from referrals to our Department for treatment of FI in November 2008-January 2010. Eligible patients were injected with 8 ml of NASHA Dx. Patients with a subtotal treatment effect were retreated after 2-4 weeks. The change in number of fecal incontinence episodes, the proportion of responders defined as at least 50% decrease in number of FI episodes and side effects were the main outcome measures. RESULTS: Sixteen patients, 15 women and 1 man with a median age of 68, 5 (range 44-80) years and a median CCFIS of 15 (range 10-19) were included in the study. The median number of incontinence episodes decreased from 21.5 (range 8-61) at baseline to 10 (range 0-30) at 6 months (p = 0.003) and 6 (range 0-44) at 12 months (p = 0.05). The median number of incontinence episodes in the 11 patients completing the 10-year follow-up was 26.5 (range 0-68). The percentage of responders at 12 months and 10 years were 56% and 27%, respectively. Mild to moderate pain at the injection site was described by 69%. There was one case of mild infection, successfully treated with antibiotics and one implant had to be removed due to dislocation. CONCLUSIONS: NASHA Dx as an intersphincteric implant improves incontinence symptoms in the short term with moderate side effects and can be used alone or as an adjunct to other treatment modalities. Long-term efficacy was observed in 27%.

Assessing the faecal source sensitivity and specificity of ruminant and human genetic microbial source tracking markers in the central Ethiopian highlands.

This study tested genetic microbial source tracking (MST) methods for identifying ruminant- (BacR) and human-associated (HF183/BacR287, BacHum) bacterial faecal contaminants in Ethiopia in a newly created regional faecal sample bank (n = 173). BacR performed well, and its marker abundance was high (100% sensitivity (Sens), 95% specificity (Spec), median log10 8·1 marker equivalents (ME) g-1 ruminant faeces). Human-associated markers tested were less abundant in individual human samples (median: log10 5·4 and 4·2 (ME + 1) g-1 ) and were not continuously detected (81% Sens, 91% Spec for BacHum; 77% Sens, 91% Spec for HF183/BacR287). Furthermore, the pig-associated Pig2Bac assay was included and performed excellent (100% Sens, 100% Spec). To evaluate the presence of MST targets in the soil microbiome, representative soil samples were tested during a whole seasonal cycle (n = 60). Only BacR could be detected, but was limited to the dry season and to sites of higher anthropogenic influence (log10 3·0 to 4·9 (ME + 1) g-1 soil). In conclusion, the large differences in marker abundances between target and non-target faecal samples (median distances between distributions ≥log10 3 to ≥log10 7) and their absence in pristine soil indicate that all tested assays are suitable candidates for diverse MST applications in the Ethiopian area.

Long-term functional results after excisional haemorrhoidectomy.

AIM: The aim of this work was to perform a long-term evaluation of a randomized trial focusing on functional aspects after excisional haemorrhoidectomy with a minimum follow-up of 9 years. METHOD: A questionnaire-based study including patients operated on for haemorrhoids in Sweden between 1999 and 2003. A total of 225 patients were randomized to Milligan's or Ferguson's operation. Twenty-six patients had died and 151 (76%) participated after a median follow-up of 10.7 years (range 9.2-12.6 years). RESULTS: Seventy-seven patients were in the Milligan group and 74 in the Ferguson group. Forty-eight (32%) reported recurrence. Anal bleeding was reported in 80% at baseline but in 28% at long-term follow-up (P < 0.0001). At baseline, 49% had spontaneous anal pain and 25% pain at defaecation. At follow-up, these figures were 17% and 11%. At follow-up, 19% described a sense of anal stenosis. At baseline, soiling was reported in 51% but in 20% at long-term follow-up (P < 0.001). Nineteen per cent used pads preoperatively and 6% at follow-up (P < 0.0001). Straining at defaecation was reported by 35% at baseline. At follow-up, this figure was 25% (P = 0.055). CONCLUSION: Symptoms associated with haemorrhoids were reduced at long-term follow-up. The most common problems were perceived recurrence and a sense of anal stenosis.

Long-term outcome after segmental colonic resection for slow transit constipation.

PURPOSE: Colectomy with ileorectal anastomosis (IRA) is the most common surgical procedure for slow transit constipation (STC). A hemicolectomy has been suggested as an alternative to IRA with good short-term results. However, long-term results are unknown. The aim of this study was to evaluate the long-term results after hemicolectomy as a treatment for STC. METHODS: Fifty patients with STC were selected for right- or left-sided hemicolectomy after evaluation with colonic scintigraphy from 1993 to 2008. Living patients (n = 43) received a bowel function questionnaire and a questionnaire about patient-reported outcome. RESULTS: After a median follow-up of 19.8 years, 13 patients had undergone rescue surgery (n = 12) or used irrigation (n = 1) and were classified as failures. In all, 30 were evaluable for functional outcome and questionnaire data for 19 patients (due to 11 non-responding) could be analysed. Two reported deterioration after several years and were also classified as failures. Median stool frequency remained increased from 1 per week at baseline to 5 per week at long-term follow-up (p = 0.001). Preoperatively, all patients used laxatives, whereas 12 managed without laxatives at long-term follow-up (p = 0.002). There was some reduction in other constipation symptoms but not statically significant. In the patients' global assessment, 10 stated a very good result, seven a good result and two a poor result. CONCLUSIONS: Hemicolectomy for STC increases stool frequency and reduces laxative use. Long-term success rate could range between 17/50 (34%) and 35/50 (70%) depending on outcome among non-responders.

Abdominal decompression illness following repetitive diving: a case report and review of the literature.

The complete pathophysiology of decompression illness is not yet fully understood. What is known is that the longer a diver breathes pressurized air at depth, the more likely nitrogen bubbles are to form once the diver returns to surface [1]. These bubbles have varying mechanical, embolic and biochemical effects on the body. The symptoms produced can be as mild as joint pain or as significant as severe neurologic dysfunction, cardiopulmonary collapse or death. Once clinically diagnosed, decompression illness must be treated rapidly with recompression therapy in a hyperbaric chamber. This case report involves a middle-aged male foreign national who completed three dives, all of which incurred significant bottom time (defined as: "the total elapsed time from the time the diver leaves the surface to the time he/she leaves the bottom)" [2]. The patient began to develop severe abdominal and back pain within 15 minutes of surfacing from his final dive. This case is unique, as his presentation was very concerning for other medical catastrophes that had to be quickly ruled out, prior to establishing the diagnosis of severe decompression illness. After emergency department resuscitation, labs and imaging were obtained; abdominal decompression illness was confirmed by CT, revealing a significant abdominal venous gas burden.

Libertas: a phase II placebo-controlled study of NRL001 in patients with faecal incontinence showed an unexpected and sustained placebo response.

PURPOSE: Faecal incontinence (FI) is distressing, significantly reduces quality of life (QoL) and has few pharmacological treatments. The α1-adrenoceptor agonist NRL001 (1R,2S-methoxamine hydrochloride) improves anal sphincter tone. NRL001 efficacy was evaluated by changes in Wexner scores at week 4 vs. baseline in NRL001-treated patients compared with placebo. Impact of NRL001 on QoL and safety were also assessed. METHODS: Four hundred sixty-six patients received NRL001 (5, 7.5 or 10 mg) or placebo as suppository, once daily over 8 weeks. Wexner score, Vaizey score and QoL were analysed at baseline, week 4 and week 8. FI episodes and adverse events were recorded in diaries. RESULTS: At week 4, mean reductions in Wexner scores were -3.0, -2.6, -2.6 and -2.4 for NRL001 5, 7.5, 10 mg and placebo, respectively. All reduced further by week 8. As placebo responses also improved, there was no significant treatment effect at week 4 (p = 0.6867) or week 8 (p = 0.5005). FI episode frequency improved for all patients, but not significantly compared with placebo (week 4: p = 0.2619, week 8: p = 0.5278). All patients' QoL improved, but not significantly for all parameters (p > 0.05) except depression/self-perception at week 4 (p = 0.0102) and week 8 (p = 0.0069), compared with placebo. Most adverse events were mild and judged probably or possibly related to NRL001. CONCLUSIONS: All groups demonstrated improvement in efficacy and QoL compared with baseline. NRL001 was well-tolerated without serious safety concerns. Despite the improvement in all groups, there was no statistically significant treatment effect, underlining the importance of relating results to a placebo arm.

Adjunctive retigabine in refractory focal epilepsy: Postmarketing experience at four tertiary epilepsy care centers in Germany.

PURPOSE: Retigabine (RTG, ezogabine) is the first potassium channel-opening anticonvulsant drug approved for adjunctive treatment of focal epilepsies. We report on the postmarketing clinical efficacy, adverse events, and retention rates of RTG in adult patients with refractory focal epilepsy. METHODS: Clinical features before and during RTG treatment were retrospectively collected from patients treated at four German epilepsy centers in 2011 and 2012. RESULTS: A total of 195 patients were included. Daily RTG doses ranged from 100 to 1500 mg. Retigabine reduced seizure frequency or severity for 24.6% and led to seizure-freedom in 2.1% of the patients but had no apparent effect in 43.1% of the patients. Seizure aggravation occurred in 14.9%. The one-, two-, and three-year retention rates amounted to 32.6%, 7.2%, and 5.7%, respectively. Adverse events were reported by 76% of the patients and were mostly CNS-related. Blue discolorations were noted in three long-term responders. Three possible SUDEP cases occurred during the observation period, equalling an incidence rate of about 20 per 1000 patient years. CONCLUSIONS: Our results are similar to other pivotal trials with respect to the long-term, open-label extensions and recent postmarketing studies. Despite the limitations of the retrospective design, our observational study suggests that RTG leads to good seizure control in a small number of patients with treatment-refractory seizures. However, because of the rather high percentage of patients who experienced significant adverse events, we consider RTG as a drug of reserve.

Long-term outcome after surgery for Crohn's anal fistula.

AIM: Treatment of Crohn's anal fistula remains challenging and little is known about factors associated with healing. The aim of this study was to assess the rate of healing after surgical treatment and analyse clinical variables related to healing. METHOD: A total of 119 patients [63 women, mean age 36 (±13.7) years] with histopathologically verified Crohn's disease underwent a surgical procedure for anal fistula at four main referral centres in Sweden, January 1998 to December 2009. Baseline and treatment-related variables were recorded and analysed for correlation with fistula healing at a final follow-up after a mean of 7.2 (median 7.1, 1.0-17.5) years. RESULTS: Of the 119 patients 62 (52%) were healed at final follow-up. Fourteen healed after one procedure and the remaining 48 healed after a further median of 4.0 (2-20) procedures. Ten (8%) patients were subjected to a proctectomy. Final healing was more common in patients operated with a procedure aiming at eradicating the fistula (P = 0.0001), without proctitis (P = 0.02) and a shorter duration of Crohn's disease (P = 0.0019). CONCLUSION: Long-term healing of a Crohn's anal fistula can be expected in about half of the patients, usually after repeated surgical treatment. The probability for cure was higher when a curative operation was performed in a patient without proctitis and with a shorter duration of Crohn's disease. An attempt to close a Crohn's anal fistula is thus often worthwhile.

Efficacy of LIFT for recurrent anal fistula.

AIM: Ligation of the intersphincteric fistula tract (LIFT) is a novel sphincter-preserving technique for anal fistula. This pilot study was designed to evaluate the results in patients with a recurrent fistula. METHOD: Seventeen patients [nine men; median age 49 (range, 30-76) years] with a recurrent trans-sphincteric fistula were treated with a LIFT procedure between June 2008 and February 2011. All were followed prospectively for a median of 16 (range, 5-27) weeks with clinical examination. Fifteen followed for 13.5 (range, 8-26) months by clinical examination also had three-dimensional (3D) anal ultrasound. RESULTS: The duration of the procedure was 35 (range, 18-70) min. One patient developed a small local haematoma and one had a subcutaneous infection, but otherwise there was no morbidity. At follow up, 11 (65%) patients had a successful closure, two (12%) had a remaining sinus and four (23%) had a persistent fistula. The incidence of persistent or recurrent fistulae at 13.5 months was six (40%) of 15 patients. No de novo faecal incontinence was reported. CONCLUSION: LIFT is a safe procedure for patients with recurrent anal fistula, with healing at short-term and medium-term follow-up comparable with or superior to that of other sphincter-preserving techniques. Larger studies with a longer follow up are needed to define the ultimate role of LIFT in patients with recurrence.

Effect of local gentamicin-collagen on perineal wound complications and cancer recurrence after abdominoperineal resection: a multicentre randomized controlled trial.

AIM: Perineal wound sepsis is a common problem after abdominoperineal resection of the rectum (APR), with a reported incidence of 10-15% in previously non-irradiated patients, 20-30% in patients given preoperative radiation and 50% among patients submitted to preoperative radiation combined with chemotherapy. The local application of gentamicin-collagen was evaluated to determine whether its use in the perineal wound reduced risk complications and had an effect on cancer recurrence. METHOD: In this prospective multicentre (seven hospitals) randomized controlled trial, 102 patients undergoing APR due to cancer or benign disease were randomized into two groups including surgery with gentamicin-collagen (GS+, n = 52) or surgery without gentamicin-collagen (GS-, n = 50). Patients were followed at 7, 30 and 90 days and at 1 and 5 years. RESULTS: There were no statistically significant differences between the two groups regarding perineal wound complications, infectious or non-infectious, or cancer recurrence. CONCLUSION: There was no statistically significant effect on perineal wound complications or cancer recurrence following the local administration of gentamicin-collagen during APR.

Efficacy and quality of life 2 years after treatment for faecal incontinence with injectable bulking agents.

BACKGROUND: Stabilized non-animal hyaluronic acid/dextranomer (NASHA Dx) gel as injectable bulking therapy has been shown to decrease symptoms of faecal incontinence, but the durability of treatment and effects and influence on quality of life (QoL) is not known. The aim of this study was to assess the effects on continence and QoL and to evaluate the relationship between QoL and efficacy up to 2 years after treatment. METHODS: Thirty-four patients (5 males, mean age 61, range 34-80) were injected with 4 × 1 ml NASHA Dx in the submucosal layer. The patients were followed for 2 years with registration of incontinence episodes, bowel function and QoL questionnaires. RESULTS: Twenty-six patients reported sustained improvement after 24 months. The median number of incontinence episodes before treatment was 22 and decreased to 10 at 12 months (P = 0.0004) and to 7 at 24 months (P = 0.0026). The corresponding Miller incontinence scores were 14, 11 (P = 0.0078) and 10.5 (P = 0.0003), respectively. There was a clear correlation between the decrease in the number of leak episodes and the increase in the SF-36 Physical Function score but only patients with more than 75 % improvement in the number of incontinence episodes had a significant improvement in QoL at 24 months. CONCLUSIONS: Anorectal injection of NASHA Dx gel induces improvement of incontinence symptoms for at least 2 years. The treatment has a potential to improve QoL. A 75 % decrease in incontinence episodes may be a more accurate threshold to indicate a successful incontinence treatment than the more commonly used 50 %.

The impact on postoperative outcomes of intraoperative fluid management strategies during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The impact of intraoperative fluid management during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on postoperative outcomes has been poorly investigated. This study aimed to retrospectively evaluate the impact of intraoperative fluid management strategy on postoperative outcomes and survival. METHODS: 509 patients undergoing CRS and HIPEC at Uppsala University Hospital/Sweden 2004-2017 were categorized into two groups according to the intraoperative fluid management strategy: pre-goal directed therapy (pre-GDT) and goal directed therapy (GDT), where a hemodynamic monitor (CardioQ or FloTrac/Vigileo) was used to optimize fluid management. Impact on morbidity, postoperative hemorrhage, length-of-stay and survival was analyzed. RESULTS: The pre-GDT group received higher fluid volume compared to the GDT group (mean 19.9 vs. 16.2 ml/kg/h, p < 0.001). Overall postoperative morbidity Grade III-V was higher in the GDT group (30% vs. 22%, p = 0.03). Multivariable adjusted odds ratio (OR) for Grade III-V morbidity was 1.80 (95%CI 1.10-3.10, p = 0.02) in the GDT group. Numerically, more cases of postoperative hemorrhage were found in the GDT group (9% vs. 5%, p = 0.09), but no correlation was observed in the multivariable analysis 1.37 (95%CI 0.64-2.95, p = 0.40). An oxaliplatin regimen was a significant risk factor for postoperative hemorrhage (p = 0.03). Mean length of stay was shorter in the GDT group (17 vs. 26 days, p < 0.0001). Survival did not differ between the groups. CONCLUSION: While GDT increased the risk for postoperative morbidity, it was associated with shortened hospital stay. Intraoperative fluid management during CRS and HIPEC did not affect the postoperative risk for hemorrhage, while the use of an oxaliplatin regimen did.

Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study.

BACKGROUND: Cytoreductive surgery and intraperitoneal chemotherapy has improved prognosis in patients with peritoneal carcinomatosis. The main modes of intraperitoneal chemotherapy treatment are peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic sequential postoperative intraperitoneal chemotherapy (SPIC). The aim of this study was to compare HIPEC and SPIC with respect to overall survival, disease-free survival, morbidity, and mortality in patients with peritoneal carcinomatosis from colon cancer. PATIENTS AND METHODS: A matched case-control study was conducted in patients with surgical macroscopic complete removal of carcinomatosis; matching was according to the peritoneal cancer index score. Thirty-two patients were included, 16 in each group (HIPEC and SPIC). Overall survival, disease-free survival, morbidity, mortality, and clinicopathological parameters were compared. RESULTS: Median overall survival was 36.5 months in the HIPEC group and 23.9 months in the SPIC group (P = 0.01). Median disease-free survival for these groups was 22.8 (HIPEC) and 13.0 months (SPIC; P = 0.02). Morbidity was not statistically different, 19% in SPIC and 37% in HIPEC. Postoperative mortality was observed in one patient in each group. CONCLUSION: HIPEC was associated with improved overall survival and disease-free survival compared with SPIC at similar morbidity and mortality, suggesting that HIPEC is the treatment of choice in colonic peritoneal carcinomatosis.

Comparison of four surgical approaches for rectal prolapse: multicentre randomized clinical trial.

BACKGROUND: Several different procedures have been described for surgical treatment of rectal prolapse and consensus on the optimal approach has not been reached. The Swedish Rectal Prolapse Trial was performed with the aim to compare the outcomes after the most common surgical approaches to rectal prolapse. METHOD: A multicentre randomized trial was conducted from 2000 to 2009. Patients were randomized between a perineal or an abdominal approach for correction of rectal prolapse (randomization A) if eligible for any procedures. Patients considered unsuitable for random allocation were only included in randomizations B or C. Patients in randomization B (perineal group) were randomized to Delorme's or Altemeier's procedures and those in randomization C (abdominal group) to suture rectopexy or resection rectopexy. Primary outcomes were bowel function and quality of life, measured using Wexner incontinence score and RAND-36, and secondary outcomes were complications and recurrence at 3 years. RESULTS: During the study period, 134 patients were randomized: 18 in randomization A group, 80 in randomization B group and 54 in randomization C group; of these, 122 patients underwent surgery. Mean follow-up was 2.6 years. Improvements in Wexner and RAND-36 scores were seen but with no significant difference between the groups. Health change scores were significantly improved from baseline up to 1 year after surgery (P < 0.001). At 3 years, recurrence rates were two of seven patients for abdominal versus five of eight patients for perineal approach (P = 0.315), 18 of 31 patients (58 per cent) for Delorme's versus 15 of 30 patients (50 per cent) for Altemeier's (P = 0.611) and four of 19 patients (21 per cent) for suture rectopexy versus two of 21 patients (10 per cent) for resection rectopexy (P = 0.398). There were no significant differences regarding postoperative complications. CONCLUSION: For all procedures, significant improvements from baseline in health change scores were noted after surgery. Recurrence rates were higher than previously reported. Registration number: NCT04893642 (http://www.clinicaltrials.gov).

Morbidity following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases with or without early postoperative intraperitoneal chemotherapy: A propensity score matched study.

BACKGROUND: Combining hyperthermic intraperitoneal chemotherapy (HIPEC) treatment with early postoperative intraperitoneal chemotherapy (EPIC) may increase postoperative morbidity. This study aims to investigate postoperative morbidity after HIPEC+EPIC compared with HIPEC alone in patients with peritoneal metastases (PM). MATERIALS AND METHODS: This is a retrospective propensity score matched cohort study. All patients undergoing PM treatment at Uppsala University Hospital between February 2004 and December 2014 were included. Propensity score matching with a 1:1 ratio was performed using sex, primary tumor site, preoperative chemotherapy, peritoneal cancer index, completeness of cytoreduction score, and HIPEC regimen. Length of hospital stay, morbidity, reoperation rate, and readmission rate within 6 months were selected as endpoints. RESULTS: A total of 390 consecutive patients were divided in two arms: HIPEC+EPIC (n = 115) and HIPEC alone (n = 275). The propensity score matching (n = 190) was successful with balanced covariates: 95 patients/arm. The length of stay (LOS) was longer in the HIPEC + EPIC group in the total cohort (30 vs 24 days, p < 0.001), with a trend towards significance in the propensity matched group (29 vs 25 days, p = 0.062). No other differences in endpoints were found. CONCLUSION: HIPEC+EPIC is associated with a prolonged hospital stay, but with no statistically significant relevant increase in postoperative morbidity, reoperation rate or incidence of readmission.

The incidence and prognostic importance of ovarian involvement in patients with peritoneal metastasis undergoing CRS-HIPEC.

BACKGROUND: Oophorectomy is a common procedure in women with peritoneal metastasis (PM) undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), which has unique consequences on hormonal balance and fertility before menopause. The objective of this study was to analyze histopathological results and the prognostic influence of ovarian involvement. MATERIAL AND METHODS: A prospective HIPEC database was used to identify 442 patients with PM from colorectal cancer, pseudomyxoma peritonei and appendix cancer scheduled for CRS-HIPEC between 2012 and 2019 at the University Hospital, Uppsala, Sweden. Statistical analyses were performed using the Chi-square test and Cox regression analysis. RESULTS: In all, 103 of 180 females underwent oophorectomy. Unilateral oophorectomy was performed in 19% (n = 20) and bilateral oophorectomy in 81% (n = 83). The median age was 61 (range 20-80). Benign ovarian histopathology was seen in 23% (n = 24). Of these, two patients were ≤35 years and 8 patients ≤50 years. The median peritoneal cancer index (PCI) was 16 in women undergoing oophorectomy, and 7 in those with no oophorectomy. Bilateral oophorectomy was associated with negative impact on overall survival (HR 4.84; 95% CI; 1.14-20.61). Malignant ovarian histopathology was also associated with a negative impact on overall survival (p = 0.043). CONCLUSION: Almost a quarter of the patients had benign histopathology after oophorectomy. This is crucial information for females with childbearing potential when planning for extensive surgery. Extensive pelvic peritoneal cancer growth resulted more often in bilateral oophorectomy which influenced survival negatively.

Identification of copy number variants on human chromosome 22 in patients with a variety of clinical findings.

The aims of this study were to create a copy number variant (CNV) profile of human chromosome 22 and to establish a genotype-phenotype correlation for patients with genomic abnormalities on chromosome 22. Thus, 1,654 consecutive pediatric patients with a diversity of clinical findings were evaluated by high-resolution chromosomal microarray analysis (CMA). We identified 25 individuals with abnormal CNVs on chromosome 22, representing 1.5% of the cases analyzed in this cohort. Meanwhile, we detected 1,298 benign CNVs on this chromosome in these individuals. Twenty-one of the 25 abnormal CNVs and the majority of the benign CNVs occurred through involvement of the 8 unstable genomic regions enriched with low copy repeats (LCR22A-H). The highly dynamic status of LCR22s within the 22q11 region facilitates the formation of diverse genomic abnormalities. This CNV profile provides a general perspective of the spectrum of chromosome 22 genomic imbalances and subsequently improves the CNV-phenotype correlations.

Multiple stressor effects on benthic macroinvertebrates in very large European rivers - A typology-based evaluation of faunal responses as a basis for future bioassessment.

Two factors complicate the ecological status classification of very large rivers in Europe according to the EU Water Framework Directive: First, current assessment methods do not fully consider the specific ecology of very large rivers (such as lateral connectivity and the role of floodplains for ecological status). Second, most of Europe's very large rivers have been severely altered by human activities such as flood protection, damming and navigation. The aim of our study is to develop an assessment method for very large rivers by identifying suitable biological metrics as the basis for multi-metric bioassessment using benthic invertebrates. Based on the pan-European typology of very large rivers by Borgwardt et al. (2019), we established a river type-specific assessment approach using invertebrate samples from 25 European countries and 94 very large rivers. The frequency and intensity of eight pressures jointly acting on the sampling sites were described, and a selection of suitable invertebrate community metrics were correlated with the pressure intensities to establish pressure-response relationships. The very large river types differ in terms of relevant pressures and pressure combinations, with the invertebrate communities distinctly responding to these pressure patterns. Neozoa dominance correlated strongly with 'navigation', being a major pressure at very large rivers, which entails severe hydro-morphological alterations such as channelization, riparian vegetation alteration and impoundment. Under combined pressures, a critical community turnover became evident in terms of neozoa outnumbering EPT taxa and the ratio of hemilimnic invertebrates decreasing. We propose ten bioassessment metrics, including measures of biological diversity as well as newly generated indicators, for the development of a European type-specific assessment method for very large rivers.

Telomere capture as a frequent mechanism for stabilization of the terminal chromosomal deletion associated with inverted duplication.

We report 4 interstitial inverted duplications with associated terminal deletions (inv dup del) involving the short arms of chromosomes 5 and 8, and the long arm of chromosome 13 by microarray-based comparative genomic hybridization (aCGH) combined with chromosome banding (GTG banding) and fluorescence in situ hybridization (FISH) analyses. Formation of the intermediate dicentric chromosomes in 3 of them occurred through breakage-fusion-bridge cycle mechanism (U-type exchange mechanism) and in the fourth one it occurred through the mediation of the inverted low-copy repeats on chromosome 8p23.1. Two of these 4 inv dup del were confirmed and a third one was suspected to be associated with telomere capture for the healing of the terminal deletions. These findings indicate that a telomere capture mechanism is frequently used for stabilizing the broken chromosome ends in this type of genomic rearrangements. In addition, the inv dup del(13) represents the first observation of inv dup del on chromosome 13 in humans, the inv dup del(5) represents the first observation of inv dup del(5p) with an associated telomere capture, and unique features of the remaining two inv dup del(8p) were also discussed.

Adaptive changes of the vestibulo-ocular reflex in flatfish are achieved by reorganization of central nervous pathways.

Flatfish provide a natural model for the study of adaptive changes in the vestibulo-ocular reflex system. During metamorphosis their vestibular and oculomotor coordinate systems undergo a 90 degree relative displacement. As a result, during swimming movements different types of compensatory eye movements are produced before and after metamorphosis by the same vestibular stimulation. Intracellular staining of central nervous connections in the flatfish with horseradish peroxidase revealed that in postmetamorphic fish secondary horizontal semicircular canal neurons contact vertical eye muscle motoneuron pools on both sides of the brain via pathways that are absent in all other vertebrates studied.