Rectal axis and enterocele on proctogram may predict laparoscopic ventral mesh rectopexy outcomes for rectal intussusception.

BACKGROUND: Laparoscopic ventral mesh rectopexy (LVMR) has become a well-established treatment for symptomatic high-grade internal rectal prolapse. The aim of this study was to identify proctographic criteria predictive of a successful outcome. METHODS: One hundred and twenty consecutive patients were evaluated from a prospectively maintained pelvic floor database. Pre- and post-operative functional results were assessed with the Wexner constipation score (WCS) and Fecal Incontinence Severity Index (FISI). Proctogram criteria were analyzed against functional results. These included grade of intussusception, presence of enterocele, rectocele, excessive perineal descent and the orientation of the rectal axis at rest (vertical vs. horizontal). RESULTS: Ninety-one patients completed both pre- and post-operative follow-up questionnaires. Median pre-operative WCS was 14 (range 10-17), and median FISI was 20 (range 0-61), with 28 patients (31%) having a FISI above 30. The presence of an enterocele was associated with more frequent complete resolution of obstructed defecation (70 vs. 52%, p = 0.02) and fecal incontinence symptoms (71 vs. 38%, p = 0.01) after LVMR. Patients with a more horizontal rectum at rest pre-operatively had significantly less resolution of symptoms post-operatively (p = 0.03). CONCLUSIONS: These data show that proctographic findings can help predict functional outcomes after LVMR. Presence of an enterocele and a vertical axis of the rectum at rest may be associated with a better resolution of symptoms.

Comprehensive genome-wide evaluation of lapatinib-induced liver injury yields a single genetic signal centered on known risk allele HLA-DRB1*07:01.

Lapatinib is associated with a low incidence of serious liver injury. Previous investigations have identified and confirmed the Class II allele HLA-DRB1*07:01 to be strongly associated with lapatinib-induced liver injury; however, the moderate positive predictive value limits its clinical utility. To assess whether additional genetic variants located within the major histocompatibility complex locus or elsewhere in the genome may influence lapatinib-induced liver injury risk, and potentially lead to a genetic association with improved predictive qualities, we have taken two approaches: a genome-wide association study and a whole-genome sequencing study. This evaluation did not reveal additional associations other than the previously identified association for HLA-DRB1*07:01. The present study represents the most comprehensive genetic evaluation of drug-induced liver injury (DILI) or hypersensitivity, and suggests that investigation of possible human leukocyte antigen associations with DILI and other hypersensitivities represents an important first step in understanding the mechanism of these events.

The treatment of all MRI-defined low rectal cancers in a single expert centre over a 5-year period: is there room for improvement?

AIM: Outcomes following treatment for low rectal cancer still remain inferior to those for upper rectal cancer. A clear definition of 'low' rectal cancer is lacking and consensus is more likely using a definition based on MRI criteria. This study aimed to determine disease presentation and treatment outcome of low rectal cancer based on a strict anatomical definition. METHOD: A low rectal cancer was defined as one with a lower border below the pelvic attachment of the levator muscles on sagittal MRI. One hundred and eighty consecutive patients with tumours defined by this criterion between 2006 and 2011 were identified from a prospectively managed departmental database. RESULTS: One hundred and eighteen patients (66%) underwent curative resection and 12 (7%) palliative resection. Eleven patients (6%) were entered into a 'watch and wait' (W&W) protocol; 10 others (5%) were not fit to undergo any operation. Some 26 patients (14%) had nonresectable local or metastatic disease. An R0 resection was the most important factor influencing survival after curative surgery. R+ resections occurred in 12% of non-abdominoperineal excisions, 11% of abdominoperineal excisions and 47% of extended resections. Overall survival was similar in the curative resections compared with the W&W patients. In 23 of the 96 (24%) treated with neoadjuvant chemoradiotherapy there was a persistent clinical or a pathological complete response. CONCLUSION: In curative resections, a clear margin is the most important determinant of survival. In 24% of the patients treated with neoadjuvant chemoradiotherapy, surgery could potentially have been avoided. There is scope for improvement in the treatment of locally advanced rectal cancers.

Transanal endoscopic microsurgery for rectal cancer.

Since its introduction in the 1980s, total mesorectal excision (TME) has been the standard surgical technique for treating rectal cancer. This procedure involves removing the rectum and the surrounding envelope of fat along the plane of the mesorectal fascia. Resecting this embryological unit reduces the local recurrence rate by removing all local lymph nodes, including those with occult metastatic disease; however, this surgery is associated with mortality and morbidity. Complications include incontinence for patients given an anastomosis, long-term stoma formation, and sexual and bladder dysfunction. Local excision of rectal cancer using the transanal endoscopic microsurgery (TEM) technique is associated with fewer complications, and therefore, is used as an alternative in specific circumstances. We outline the technique, its indications, imaging appearances and complications.

How useful is endorectal ultrasound in the management of early rectal carcinoma?

INTRODUCTION: Endorectal ultrasonography (EUS) is used to T stage early rectal tumours and select patients to whom transanal endoscopic microsurgery (TEM) could be offered. Published papers have shown that EUS can have good accuracy, but there is little literature on how EUS influences patient management. The study aim is to ascertain the value of EUS in the management of early rectal tumours. METHODS: Patients with adenomas/early rectal carcinoma being considered for TEM were prospectively studied. Each patient underwent EUS. The surgeon recorded the expected T stage, confidence level of the T stage and management plan for each patient on a proforma before and after the ultrasound result was revealed. Comparison was made between the ultrasound stage and final pathological stage where available. RESULTS: Ninety-six patients were referred over 2 years. Nine were out of reach of the rigid probe and were excluded. Proformas were completed on 53/87 patients (age range 28-87 years, mean age 66 years, 30 males/23 females). Forty-eight patients had a pathological report to compare with the EUS T stage. Ultrasound agreed with the pathological T staging in 43 patients (90%). Patient management was changed in five patients. In 30% of (16/53) patients, EUS increased the confidence level for T staging. CONCLUSION: Although EUS has a high accuracy in predicting the T stage of early rectal cancers, it never changes the management plan for lesions thought to be benign. It seldom changes the pre-operative selection process when clinical examination is considered with other imaging modalities (MRI/CT). EUS should be reserved for answering specific questions in difficult cases rather than for all patients.

A brief mindfulness meditation can ameliorate the effects of exposure to idealised social media images on self-esteem, mood, and body appreciation in young women: An online randomised controlled experiment.

The study examined whether a 10-minute mindfulness meditation intervention could ameliorate effects of exposure to social media thinspiration and fitspiration images on women's self-esteem, mood, and body appreciation. A total of 162 women aged 18-42 years (M = 25.94, SD = 4.38) completed an online experiment which involved viewing thinspiration and fitspiration images before random allocation to either a brief, ten-minute mindfulness meditation audio intervention or a ten-minute control audio about jujitsu. Participants completed self-reported measures of self-esteem, positive and negative mood, and body appreciation at baseline (Time 1), post-exposure to idealised social media images (Time 2), and immediately post-intervention (Time 3). Mixed, repeated-measures ANOVAs showed that scores were lower for body appreciation, self-esteem, and positive mood, and higher for negative mood, in both groups after exposure to idealised imagery. However, a brief mindfulness intervention ameliorated the negative effects of social media exposure. Specifically, self-esteem, body appreciation, and mood were higher in the mindfulness meditation group at Time 3, compared to the control group. Future interventions should explore the utility of mindfulness practices to provide long term buffering effects against such social media content, as well as targeting the idealisation of female physiques portrayed in thinspiration and fitspiration content.

Exploration of the polymorphic solid-state landscape of an amide-linked organic cage using computation and automation.

Organic cages can possess complex, functionalised cavities that make them promising candidates for synthetic enzyme mimics. Conformationally flexible, chemically robust structures are needed for adaptable guest binding and catalysis, but rapidly exchanging systems are difficult to resolve in solution. Here, we use low-cost calculations and high-throughput crystallisation to identify accessible conformers of a recently reported organic cage by 'locking' them in the solid state. The conformers exhibit varying distances between the internal carboxylic acid groups, suggesting adaptability for binding a wide array of target guest molecules.

Enabling batch and microfluidic non-thermal plasma chemistry: reactor design and testing.

Non-thermal plasma (NTP) is a promising state of matter for carrying out chemical reactions. NTP offers high densities of reactive species, without the need for a catalyst, while operating at atmospheric pressure and remaining at moderate temperature. Despite its potential, NTP cannot be used comprehensively in reactions until the complex interactions of NTP and liquids are better understood. To achieve this, NTP reactors that can overcome challenges with solvent evaporation, enable inline data collection, and achieve high selectivity, high yield, and high throughput are required. Here, we detail the construction of i) a microfluidic reactor for chemical reactions using NTP in organic solvents and ii) a corresponding batch setup for control studies and scale-up. The use of microfluidics enables controlled generation of NTP and subsequent mixing with reaction media without loss of solvent. The construction of a low-cost custom mount enables inline optical emission spectroscopy using a fibre optic probe at points along the fluidic pathway, which is used to probe species arising from NTP interacting with solvents. We demonstrate the decomposition of methylene blue in both reactors, developing an underpinning framework for applications in NTP chemical synthesis.

Clinical implications of preoperative echocardiographic findings on cardiovascular outcomes following vascular surgery: An observational trial.

INTRODUCTION: Peripheral artery disease and cardiac disease are often comorbid conditions. Echocardiography is a diagnostic tool that can be performed preoperatively to risk stratify patients by a functional cardiac test. We hypothesized that ventricular dysfunction and valvular lesions were associated with an increased incidence of expanded major adverse cardiac events (Expanded MACE). METHODS AND MATERIALS: Retrospective cohort study from 2011 to 2020 including all patients from a major academic center who had vascular surgery and an echocardiographic study within two years of the index procedure. RESULTS: 813 patients were included in the study; a majority had a history of smoking (86%), an ASA score of 3 (65%), and were male (68%). Carotid endarterectomy was the most common surgery (24%) and the least common surgery was open abdominal aortic aneurysm repair (5%). We found no significant association between the echocardiographic findings of left ventricular dysfunction, right ventricular dysfunction, or valvular lesions and the postoperative development of Expanded MACE. CONCLUSIONS: The preoperative echocardiographic findings of left ventricular dysfunction, right ventricular dysfunction and moderate to severe valvular lesions were not predictive of an increased incidence of postoperative Expanded MACE. We identified a significant association between RV dysfunction and post-operative dialysis that should be interpreted carefully due to the small number of outcomes. The transition from open to endovascular surgery and advances in perioperative management may have led to improved cardiovascular outcomes. TRIAL REGISTRATION: Trial Registration: NCT04836702 (clinicaltrials.gov). https://www.google.com/search?client=firefox-b-d&q=NCT04836702.

A critical appraisal of endorectal ultrasound and transanal endoscopic microsurgery and decision-making in early rectal cancer.

AIM: Transanal endoscopic microsurgery (TEM) for early rectal cancer (ERC) gives results similar to major surgery in selected cases. Endorectal ultrasound (ERUS) is an important part of the preoperative selection process. This study reports its accuracy and impact for patients entered on the UK TEM database. METHOD: The UK TEM database comprises prospectively collected data on 494 patients. This data set was used to determine the prevalence of ERUS in preoperative staging and its accuracy by comparing preoperative T-stage with definitive pathological staging following TEM. RESULTS: ERUS was performed in 165 of 494 patients who underwent TEM for rectal cancer. It inaccurately staged rectal cancer in 44.8% of tumours: 32.7% were understaged and 12.1% were overstaged. There was no significant difference in the depth of TEM excision or R1 rate between the patients who underwent ERUS before TEM and those who did not (P = 0.73). CONCLUSION: The data show that ERUS is employed in a minority of patients with rectal cancers undergoing TEM in the UK and its accuracy in this 'Real World' practice is disappointing.

Inflammatory aneurysms of the ascending aorta: diagnosis and surgical treatment.

Inflammatory aortic aneurysms (IAAs) are rare and located mainly in the infra-renal abdominal aorta. The ascending aorta has been typically spared from this process. We report on two cases of ascending aortic inflammatory aneurysms and describe the available literature on this rare entity.

'Everybody's Different: The Appearance Game'. A randomised controlled trial evaluating an appearance-related board game intervention with children aged 9-11 years.

This study evaluated the effectiveness of an educational board game aimed at increasing knowledge of appearance-related issues, positive body image, media literacy, and acceptance of appearance diversity with British school children. Two hundred and fifty-nine children, aged 9-11 (Mage = 10.26), from three primary schools in South-West England participated in a two-arm matched cluster randomised controlled trial. Outcome measures were collected pre-, post- and at two-week follow-up. Knowledge of appearance-related issues significantly increased in the intervention group, compared to the control group post-intervention, but was not maintained at follow-up. There were no significant differences between groups for body appreciation, media literacy or acceptance of visible difference. Of the intervention arm, 78 % (n=117) they would like to play again and 85.3 % (n=128) thought other children would like to play. Qualitative data suggests participants learned the key messages of the game. The findings suggest 'Everybody's Different: The Appearance Game' is an enjoyable way to increase knowledge of appearance-related issues. In future, researchers should consider how to increase body appreciation, media literacy and acceptance of appearance diversity, for example by increasing the dosage of the game or using it in conjunction with discussions and lessons surrounding appearance diversity and appearance-altering conditions.

Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease.

Hemoglobin is an important nutrient source for intraerythrocytic malaria organisms. Its catabolism occurs in an acidic digestive vacuole. Our previous studies suggested that an aspartic protease plays a key role in the degradative process. We have now isolated this enzyme and defined its role in the hemoglobinolytic pathway. Laser desorption mass spectrometry was used to analyze the proteolytic action of the purified protease. The enzyme has a remarkably stringent specificity towards native hemoglobin, making a single cleavage between alpha 33Phe and 34Leu. This scission is in the hemoglobin hinge region, unraveling the molecule and exposing other sites for proteolysis. The protease is inhibited by pepstatin and has NH2-terminal homology to mammalian aspartic proteases. Isolated digestive vacuoles make a pepstatin-inhibitable cleavage identical to that of the purified enzyme. The pivotal role of this aspartic hemoglobinase in initiating hemoglobin degradation in the malaria parasite digestive vacuoles is demonstrated.

Novel α-ketoglutarate dioxygenase tfdA-related genes are found in soil DNA after exposure to phenoxyalkanoic herbicides.

Phenoxyalkanoic herbicides such as 2,4-dichlorophenoxyacetate (2,4-D), 2,4-dichlorophenoxybutyrate (2,4-DB) or mecoprop are widely used to control broad-leaf weeds. Several bacteria have been reported to degrade these herbicides using the α-ketoglutarate-dependent, 2,4-dichlorophenoxyacetate dioxygenase encoded by the tfdA gene, as the enzyme catalysing the first step in the catabolic pathway. The effects of exposure to different phenoxyalkanoic herbicides in the soil bacterial community and in the tfdA genes diversity were assessed using an agricultural soil exposed to these anthropogenic compounds. Total community bacterial DNA was analysed by terminal restriction fragment length polymorphism of the 16S rRNA and the tfdA gene markers, and detection and cloning of tfdA gene related sequences, using PCR primer pairs. After up to 4 months of herbicide exposure, significant changes in the bacterial community structure were detected in soil microcosms treated with mecoprop, 2,4-DB and a mixture of both plus 2,4-D. An impressive variety of novel tfdA gene related sequences were found in these soil microcosms, which cluster in new tfdA gene related sequence groups, unequally abundant depending on the specific herbicide used in soil treatment. Structural analysis of the putative protein products showed small but significant amino acid differences. These tfdA gene sequence variants are, probably, required for degradation of natural substrate(s) structurally related to these herbicides and their presence explains self-remediation of soils exposed to phenoxyalkanoic herbicides.

Enterocoele is a marker of severe pelvic floor weakness.

OBJECTIVE: The aim was to evaluate the relationship between the presence of an enterocoele and grade of rectal prolapse (RP). METHOD: Defaecating proctograms of consecutive patients presenting to the Oxford Pelvic Floor Clinic between January 2004 and November 2008 were analysed. Patients were included if they had full thickness internal (grades 1-4 prolapse) or external RP (grade 5 prolapse). All those included were analysed with regards to the presence of an enterocoele. RESULTS: Three hundred and seventy-one patients [322 (87%) women and 49 (23%) men] were found to have a degree of RP. One out of eight (12.5%) patients with grade 1 RP, 10/42 (18.5%) with grade 2 RP, 34/125 (27%) with grade 3 RP, 62/135 (46%) with grade 4 RP and 23/49 (47%) with grade 5 full thickness external RP had an enterocoele present. This was a statistically significant trend (Pearson chi(2) test P < 0.0002). There was a significantly higher proportion of enterocoeles in women [125/322 (39%) than in men (5/49 (10%)] (P < 0.0001) and a higher likelihood of having an enterocoele with advancing age (P < 0.0001). Within the study, there was no significant difference in the proportion of nulliparous and parous women with enterocoeles (P = 0.8); there were a significantly higher proportion of enterocoeles in hysterectomized women (P = 0.015). CONCLUSIONS: Enterocoele is increasingly seen with advancing RP severity. This suggests that the two findings are part of the same pelvic floor process. These data support the hypothesis that enterocoele is a marker of severe pelvic floor weakness. Enterocoele is seen more frequently in females particularly after hysterectomy.

Band occlusion of the atrial appendage.

OBJECTIVES: A new device has been developed for occlusion of the left atrial appendage (LAA). Previous investigations have been in the canine model. The canine atrial appendage does not vary in size and shape as much as the human. The goal of this study was to investigate band occlusion of right atrial appendages in the pig model, which are more broad based. METHODS: The right atrial appendages of six pigs were approached through a right thoracotomy. An expandable polyester fabric-covered silicone band was placed on the appendage. The animals were evaluated at the time of band placement with fluoroscopy, contrast injection, and in three animals, echocardiography. After one week, the animals were again evaluated with fluoroscopy. The animals were sacrificed at 12 weeks. RESULTS: Bands were placed without complication at the base of all six appendages. All appendages were effectively occluded and all bands remained at the appendage base. The healed atrial surface was consistently smooth and devoid of thrombus. CONCLUSIONS: Occlusion of a broad-based appendage as seen with human LAA is feasible with this novel band technique.

Elastin homeostasis is altered with pelvic organ prolapse in cultures of vaginal cells from a lysyl oxidase-like 1 knockout mouse model.

Pelvic organ prolapse (POP) decreases quality of life for many women, but its pathophysiology is poorly understood. We have previously shown that Lysyl oxidase-like 1 knockout (Loxl1 KO) mice reliably prolapse with age and increased parity, similar to women. Both this model and clinical studies also indicate that altered elastin metabolism in pelvic floor tissues plays a role in POP manifestation, although it is unknown if this is a cause or effect. Using Loxl1 KO mice, we investigated the effects of genetic absence of Loxl1, vaginal parity, and presence of POP on the expression of genes and proteins key to the production and regulation of elastic matrix. Cultured cells isolated from vaginal explants of mice were assayed with Fastin for elastic matrix, as well as RT-PCR and Western blot for expression of genes and proteins important for elastin homeostasis. Elastin synthesis significantly decreased with absence of LOXL1 and increased with parity (p < .001), but not with POP. Cells from prolapsed mice expressed significantly decreased MMP-2 (p < .05) and increased TIMP-4 (p < .05). The results suggest changes to elastin structure rather than amounts in prolapsed mice as well as poor postpartum elastin turnover, resulting in accumulation of damaged elastic fibers leading to abnormal tropoelastin deposition. POP may thus, be the result of an inability to initiate the molecular mechanisms necessary to clear and replace damaged elastic matrix in pelvic floor tissues after vaginal birth.

Validation of Genotyping by Sequencing Using Transcriptomics for Diversity and Application of Genomic Selection in Tetraploid Potato.

Potato is an important food crop due to its increasing consumption, and as a result, there is demand for varieties with improved production. However, the current status of breeding for improved varieties is a long process which relies heavily on phenotypic evaluation and dated molecular techniques and has little emphasis on modern genotyping approaches. Evaluation and selection before a cultivar is commercialized typically takes 10-15 years. Molecular markers have been developed for disease and pest resistance, resulting in initial marker-assisted selection in breeding. This study has evaluated and implemented a high-throughput transcriptome sequencing method for dense marker discovery in potato for the application of genomic selection. An Australian relevant collection of commercial cultivars was selected, and identification and distribution of high quality SNPs were examined using standard bioinformatic pipelines and a custom approach for the prediction of allelic dosage. As a result, a large number of SNP markers were identified and filtered to generate a high-quality subset that was then combined with historic phenotypic data to assess the approach for genomic selection. Genomic selection potential was predicted for highly heritable traits and the approach demonstrated advantages over the previously used technologies in terms of markers identified as well as costs incurred. The high-quality SNP list also provided acceptable genome coverage which demonstrates its applicability for much larger future studies. This SNP list was also annotated to provide an indication of function and will serve as a resource for the community in future studies. Genome wide marker tools will provide significant benefits for potato breeding efforts and the application of genomic selection will greatly enhance genetic progress.

Interactions Between Plant Viral Nanoparticles (VNPs) and Blood Plasma Proteins, and Their Impact on the VNP In Vivo Fates.

Plant viral nanoparticles (VNPs) are currently being developed as novel vessels for delivery of diagnostic and therapeutic cargos to sites of disease. With a rapid increase in the number of VNP variants and their potential applications in nanomedicine, the properties they acquire in the bloodstream need to be investigated. Biomolecules present in plasma are known to adsorb onto the surface of nanomaterials (including VNPs), forming a biointerface called the protein corona, which is capable of reprogramming the properties of VNPs. Here we describe a few general methods to isolate and study the VNP-protein corona complexes, in order to evaluate the impact of protein corona on molecular recognition of VNPs by target cells, and clearance by phagocytes. We outline procedures for in vivo screening of VNP fates in a mouse model, which may be useful for evaluation of efficacy and biocompatibility of different VNP based formulations.