Clinical characterization of patients with anal fistula during follow-up of anorectal abscess: a large population-based study

PurposeApproximately 15-50% of patients with an anorectal abscess will develop an anal fistula, but the true incidence of this entity is currently unknown. The aim of the study was to determine the incidence of anorectal abscess and development of a fistula in a specific population area and to identify potential risk factors associated with demographic, socioeconomic and pre-existing disease (e.g. diabetes and inflammatory bowel disease).MethodsA longitudinal observational study was designed including a large cohort study in an area with 7,553,650 inhabitants in Spain 1st january 2014 to 31st december 2019. Adults who attended for the first time with an anorectal abscess and had a minimum of 1-year follow-up were included. The diagnosis was made using ICD-10 codes for anorectal abscess and anal fistula.ResultsDuring the study period, we included 27,821 patients with anorectal abscess. There was a predominance of men (70%) and an overall incidence of 596 per million population. The overall incidence of anal fistula developing from abscesses was 20%, with predominance in men, and a lower incidence in the lowest income level. The cumulative incidence of fistula was higher in men and in younger patients (p < 0.0001). On multivariate analysis, patients aged 60-69 years (hazard ratio 2.0) and those with inflammatory bowel disease (hazard ratio 1.8-2.0) had a strong association with fistula development (hazard ratio 2.0).ConclusionsOne in five patients with an anorectal abscess will develop a fistula, with a higher likelihood in men. Fistula formation was strongly associated with inflammatory bowel disease

Cytotoxic Cembranes from Indonesian Specimens of the Soft Coral Nephthea sp

Methanol extracts of two specimens of the soft coral Nephthea sp. collected from the Seribu Islands, Indonesia, were active in an anticancer bioassay. One new (1) and four known diterpenes (2–5) based on the cembrane carbon skeleton were isolated from these extracts, as was arachidonic acid (8). The structures of all compounds were elucidated using NMR, including 1,1-ADEQUATE and 1D gradient selective NOESY where applicable to determine the relative stereochemistry. Spectroscopic data, including 1H and 13C NMR, UV, IR and optical rotations are reported when enough material was available and where this has not been done previously. Inhibition assays employing three cancer cell lines; SF-268 (CNS), MCF-7 (breast), and H460 (lung) were used to guide the isolation of all compounds

Influence of Anthropogenic Pressures on the Bioactivity Potential of Sponges and Soft Corals in the Coral Reef Environment

The wealth of marine sponges and soft corals in Indonesian waters represents a rich source of natural products. However, anthropogenic pressures potentially decrease diversity in coral reefs. Presented here are trends for tropical sponge and soft coral biodiversity and their bioactivity potential under the influence of increasing anthropogenic pressures. Samples were collected along transects (near, mid, and far) at Karimunjawa and Seribu Islands Marine National Parks and environmental parameters (salinity, pH, dissolved oxygen (DO), phosphate, nitrate, and ammonia), sponge and soft coral biodiversity, and the bioactivity potential of those organisms (50% Growth Inhibition (GI50) of cancer cell lines H460-Lung, MCF7-Breast, and SF268-CNS) are compared. The environmental conditions and biodiversity were found to be significantly different between groups of sampling sites (P<0.05). Canonical Discriminant Analysis (CDA) revealed DO was the discriminant factor driving the separation between groups (90.1%). Diversity tended to be higher in the Far group with strong and significant relation to DO (R= 0.611, P<0.05) and ammonia (R = -0.812, P<0.05). The CDA also showed that an increase in bioactivity (low % GI50) of sponge and soft coral extracts was related to a canonical function (57.21%) consisting of high DO, high pH, and low nutrients. These findings indicate the production of bioactive compounds is related to diversity and complexity of coral reef systems. Therefore, strategies for marine protection by mitigating the impacts of anthropogenic pressures needs to be optimized in order to conserve the overall environment and sustain its natural bioactivity potential indefinitely

A New Diketopiperazine, Cyclo-(4-S-hydroxy-R-proline-R-isoleucine), from an Australian Specimen of the Sponge Stelletta sp. †

While investigating the cytotoxic activity of the methanol extract of an Australian marine sponge Stelletta sp. (Demospongiae), a new diketopiperazine, cyclo-(4-S-hydroxy-R-proline-R-isoleucine) (1), was isolated together with the known bengamides; A (2), F (3), N (4), Y (5), and bengazoles; Z (6), C4 (7) and C6 (8). The isolation and structure elucidation of the diketopiperazine (1), together with the activity of 1–8 against a panel of human and mammalian cell lines are discussed

Unusual Regulation of a Leaderless Operon Involved in the Catabolism of Dimethylsulfoniopropionate in Rhodobacter sphaeroides

Rhodobacter sphaeroides strain 2.4.1 is a widely studied bacterium that has recently been shown to cleave the abundant marine anti-stress molecule dimethylsulfoniopropionate (DMSP) into acrylate plus gaseous dimethyl sulfide. It does so by using a lyase encoded by dddL, the promoter-distal gene of a three-gene operon, acuR-acuI-dddL. Transcription of the operon was enhanced when cells were pre-grown with the substrate DMSP, but this induction is indirect, and requires the conversion of DMSP to the product acrylate, the bona fide co-inducer. This regulation is mediated by the product of the promoter-proximal gene acuR, a transcriptional regulator in the TetR family. AcuR represses the operon in the absence of acrylate, but this is relieved by the presence of the co-inducer. Another unusual regulatory feature is that the acuR-acuI-dddL mRNA transcript is leaderless, such that acuR lacks a Shine-Dalgarno ribosomal binding site and 5′-UTR, and is translated at a lower level compared to the downstream genes. This regulatory unit may be quite widespread in bacteria, since several other taxonomically diverse lineages have adjacent acuR-like and acuI-like genes; these operons also have no 5′ leader sequences or ribosomal binding sites and their predicted cis-acting regulatory sequences resemble those of R. sphaeroides acuR-acuI-dddL

Air exposure of coral is a significant source of dimethylsulfide (DMS) to the atmosphere

Corals are prolific producers of dimethylsulfoniopropionate (DMSP). High atmospheric concentrations of the DMSP breakdown product dimethylsulfide (DMS) have been linked to coral reefs during low tides. DMS is a potentially key sulfur source to the tropical atmosphere, but DMS emission from corals during tidal exposure is not well quantified. Here we show that gas phase DMS concentrations (DMSgas) increased by an order of magnitude when three Indo-Pacific corals were exposed to air in laboratory experiments. Upon re-submersion, an additional rapid rise in DMSgas was observed, reflecting increased production by the coral and/or dissolution of DMS-rich mucus formed by the coral during air exposure. Depletion in DMS following re-submersion was likely due to biologically-driven conversion of DMS to dimethylsulfoxide (DMSO). Fast Repetition Rate fluorometry showed downregulated photosynthesis during air exposure but rapid recovery upon re-submersion, suggesting that DMS enhances coral tolerance to oxidative stress during a process that can induce photoinhibition. We estimate that DMS emission from exposed coral reefs may be comparable in magnitude to emissions from other marine DMS hotspots. Coral DMS emission likely comprises a regular and significant source of sulfur to the tropical marine atmosphere, which is currently unrecognised in global DMS emission estimates and Earth System Models

Induction of Larval Metamorphosis of the Coral Acropora millepora by Tetrabromopyrrole Isolated from a Pseudoalteromonas Bacterium

The induction of larval attachment and metamorphosis of benthic marine invertebrates is widely considered to rely on habitat specific cues. While microbial biofilms on marine hard substrates have received considerable attention as specific signals for a wide and phylogenetically diverse array of marine invertebrates, the presumed chemical settlement signals produced by the bacteria have to date not been characterized. Here we isolated and fully characterized the first chemical signal from bacteria that induced larval metamorphosis of acroporid coral larvae (Acropora millepora). The metamorphic cue was identified as tetrabromopyrrole (TBP) in four bacterial Pseudoalteromonas strains among a culture library of 225 isolates obtained from the crustose coralline algae Neogoniolithon fosliei and Hydrolithon onkodes. Coral planulae transformed into fully developed polyps within 6 h, but only a small proportion of these polyps attached to the substratum. The biofilm cell density of the four bacterial strains had no influence on the ratio of attached vs. non-attached polyps. Larval bioassays with ethanolic extracts of the bacterial isolates, as well as synthetic TBP resulted in consistent responses of coral planulae to various doses of TBP. The lowest bacterial density of one of the Pseudoalteromonas strains which induced metamorphosis was 7,000 cells mm−2 in laboratory assays, which is on the order of 0.1 –1% of the total numbers of bacteria typically found on such surfaces. These results, in which an actual cue from bacteria has been characterized for the first time, contribute significantly towards understanding the complex process of acroporid coral larval settlement mediated through epibiotic microbial biofilms on crustose coralline algae

The Ruegeria pomeroyi acuI Gene Has a Role in DMSP Catabolism and Resembles yhdH of E. coli and Other Bacteria in Conferring Resistance to Acrylate

The Escherichia coli YhdH polypeptide is in the MDR012 sub-group of medium chain reductase/dehydrogenases, but its biological function was unknown and no phenotypes of YhdH− mutants had been described. We found that an E. coli strain with an insertional mutation in yhdH was hyper-sensitive to inhibitory effects of acrylate, and, to a lesser extent, to those of 3-hydroxypropionate. Close homologues of YhdH occur in many Bacterial taxa and at least two animals. The acrylate sensitivity of YhdH− mutants was corrected by the corresponding, cloned homologues from several bacteria. One such homologue is acuI, which has a role in acrylate degradation in marine bacteria that catabolise dimethylsulfoniopropionate (DMSP) an abundant anti-stress compound made by marine phytoplankton. The acuI genes of such bacteria are often linked to ddd genes that encode enzymes that cleave DMSP into acrylate plus dimethyl sulfide (DMS), even though these are in different polypeptide families, in unrelated bacteria. Furthermore, most strains of Roseobacters, a clade of abundant marine bacteria, cleave DMSP into acrylate plus DMS, and can also demethylate it, using DMSP demethylase. In most Roseobacters, the corresponding gene, dmdA, lies immediately upstream of acuI and in the model Roseobacter strain Ruegeria pomeroyi DSS-3, dmdA-acuI were co-regulated in response to the co-inducer, acrylate. These observations, together with findings by others that AcuI has acryloyl-CoA reductase activity, lead us to suggest that YdhH/AcuI enzymes protect cells against damaging effects of intracellular acryloyl-CoA, formed endogenously, and/or via catabolising exogenous acrylate. To provide “added protection” for bacteria that form acrylate from DMSP, acuI was recruited into clusters of genes involved in this conversion and, in the case of acuI and dmdA in the Roseobacters, their co-expression may underpin an interaction between the two routes of DMSP catabolism, whereby the acrylate product of DMSP lyases is a co-inducer for the demethylation pathway

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Metachromins U-W: Cytotoxic merosesquiterpenoids from an Australian specimen of the sponge Thorecta reticulata

Three new merosesquiterpenoids, metachromins U, V, and W (1–3), were isolated from a specimen of the marine sponge Thorecta reticulata collected off Hunter Island, Tasmania, Australia. Structures of the new compounds were elucidated through extensive NMR investigations and comparison with literature values. The cytotoxicities of 1–3 were assessed against a panel of human tumor cell lines (SF-268, H460, MCF-7, and HT-29) and a mammalian cell line (CHO-K1). All compounds were found to have 50% growth inhibition activities in the range 2.1–130 μM, with 2 being the most active (GI50 2.1–10 μM)