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.

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.

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.

'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.

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.

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.

Reticular synthesis of porous molecular 1D nanotubes and 3D networks.

Synthetic control over pore size and pore connectivity is the crowning achievement for porous metal-organic frameworks (MOFs). The same level of control has not been achieved for molecular crystals, which are not defined by strong, directional intermolecular coordination bonds. Hence, molecular crystallization is inherently less controllable than framework crystallization, and there are fewer examples of 'reticular synthesis', in which multiple building blocks can be assembled according to a common assembly motif. Here we apply a chiral recognition strategy to a new family of tubular covalent cages to create both 1D porous nanotubes and 3D diamondoid pillared porous networks. The diamondoid networks are analogous to MOFs prepared from tetrahedral metal nodes and linear ditopic organic linkers. The crystal structures can be rationalized by computational lattice-energy searches, which provide an in silico screening method to evaluate candidate molecular building blocks. These results are a blueprint for applying the 'node and strut' principles of reticular synthesis to molecular crystals.

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.

Serum albumin 'camouflage' of plant virus based nanoparticles prevents their antibody recognition and enhances pharmacokinetics.

Plant virus-based nanoparticles (VNPs) are a novel class of nanocarriers with unique potential for biomedical applications. VNPs have many advantageous properties such as ease of manufacture and high degree of quality control. Their biocompatibility and biodegradability make them an attractive alternative to synthetic nanoparticles (NPs). Nevertheless, as with synthetic NPs, to be successful in drug delivery or imaging, the carriers need to overcome several biological barriers including innate immune recognition. Plasma opsonization can tag (V)NPs for clearance by the mononuclear phagocyte system (MPS), resulting in shortened circulation half lives and non-specific sequestration in non-targeted organs. PEG coatings have been traditionally used to 'shield' nanocarriers from immune surveillance. However, due to broad use of PEG in cosmetics and other industries, the prevalence of anti-PEG antibodies has been reported, which may limit the utility of PEGylation in nanomedicine. Alternative strategies are needed to tailor the in vivo properties of (plant virus-based) nanocarriers. We demonstrate the use of serum albumin (SA) as a viable alternative. SA conjugation to tobacco mosaic virus (TMV)-based nanocarriers results in a 'camouflage' effect more effective than PEG coatings. SA-'camouflaged' TMV particles exhibit decreased antibody recognition, as well as enhanced pharmacokinetics in a Balb/C mouse model. Therefore, SA-coatings may provide an alternative and improved coating technique to yield (plant virus-based) NPs with improved in vivo properties enhancing drug delivery and molecular imaging.

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.

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.

Genome-wide DNA methylation profiling of recurrent and non-recurrent chordomas.

Chordomas are an aggressive rare type of malignant bone tumors arising from the remnant of the notochord. Chordomas occur mainly in vertebral bones and account for 1-4% of malignant bone tumors. Management and treatment of chordomas are difficult as they are resistant to conventional chemotherapy; therefore, they are mainly treated with surgery and radiation therapy. In this study, we performed DNA methylation profiling of 26 chordomas and normal nucleus pulposus samples plus UCH-1 chordoma cell line using the Illumina Infinium HumanMethylation450 BeadChips. Combined bisulfite restriction analysis and bisulfite sequencing was used to confirm the methylation data. Gene expression was analyzed using RT-PCR before and after 5-aza-2'-deoxycytidine (5-azaDC) treatment of chordoma cell lines. Analysis of the HumanMethylation450 BeadChip data led to the identification of 8,819 loci (2.9%) that were significantly differentially methylated (>0.2 average ß-value difference) between chordomas and nucleus pulposus samples (adjusted P < 0.05). Among these, 5,868 probes (66.5%) were hypomethylated, compared to 2,951 (33.5%) loci that were hypermethylated in chordomas compared to controls. From the 2,951 differentially hypermethylated probes, 33.3% were localized in the promoter region (982 probes) and, among these, 104 probes showed cancer-specific hypermethylation. Ingenuity Pathway Analysis indicates that the cancer-specific differentially methylated loci are involved in various networks including cancer disease, nervous system development and function, cell death and survival, cellular growth, cellular development, and proliferation. Furthermore, we identified a subset of probes that were differentially methylated between recurrent and non-recurrent chordomas. BeadChip methylation data was confirmed for these genes and gene expression was shown to be upregulated in methylated chordoma cell lines after treatment with 5-azaDC. Understanding epigenetic changes in chordomas may provide insights into chordoma tumorigenesis and development of epigenetic biomarkers.

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.

Recent advances in the genetic transformation of coffee.

Coffee is one of the most important plantation crops, grown in about 80 countries across the world. The genus Coffea comprises approximately 100 species of which only two species, that is, Coffea arabica (commonly known as arabica coffee) and Coffea canephora (known as robusta coffee), are commercially cultivated. Genetic improvement of coffee through traditional breeding is slow due to the perennial nature of the plant. Genetic transformation has tremendous potential in developing improved coffee varieties with desired agronomic traits, which are otherwise difficult to achieve through traditional breeding. During the last twenty years, significant progress has been made in coffee biotechnology, particularly in the area of transgenic technology. This paper provides a detailed account of the advances made in the genetic transformation of coffee and their potential applications.

Ingesting breakfast meals of different glycaemic load does not alter cognition and satiety in children.

BACKGROUND/OBJECTIVES: The effect of Glycaemic Index (GI) and Load (GL) of breakfasts on satiety and aspects of cognitive function in children is inconclusive. We aimed to assess if isocaloric breakfasts differing in GL (by replacing high-GI carbohydrate foods with dairy protein foods) acutely alter cognitive function and satiety in 10- to 12-year-old children. SUBJECTS/METHODS: A total of 39 children, aged 11.6±0.7 years with body mass index 18.9±3.0 kg/m² (Mean±s.e.) participated in a randomised crossover trial of three isocaloric breakfasts (1.3 MJ): high GL (HGL: 7 g protein, 9 g fat, 50 g carbohydrate, GL 33); medium GL (MGL: 14 g protein, 9 g fat, 45 g carbohydrate, GL 24) and low GL (LGL: 18 g protein, 10 g fat, 38 g carbohydrate, GL 18). Blood glucose was recorded using a continuous glucose monitor. Subjective hunger and cognitive performance were measured before and hourly after consuming the test breakfast via a computer-delivered battery. Ad libitum intake at a buffet lunch meal was measured at 3 h at the end of testing. RESULTS: Incremental area under the glucose curve (iAUC) was significantly different with HGL>MGL>LGL (P<0.001). Glucose concentrations fell below baseline after 83±6 min for HGL, 63±5 min (MGL) and 67±5 min (LGL)(P=0.009). Breakfast GL did not significantly alter changes in cognitive function or self-reported satiety throughout testing. Energy intake at lunch was not significantly different between treatments (HGL 2943±168 kJ; MGL 2949±166 kJ; LGL 2993±191 kJ). CONCLUSIONS: Reducing breakfast GL by replacing carbohydrate with protein does not alter satiety or cognition over 3 h in 10- to 12-year-old children.

Prospective clinical study of a novel left atrial appendage occlusion device.

PURPOSE: This Food and Drug Administration-approved investigational device exempt trial assessed the safety and efficacy of a novel device for external left atrial appendage (LAA) exclusion. DESCRIPTION: Delivery tool and implant consisting of connectors imbedded in a compliant, soft silicone applied to the base of the LAA flush with the external wall was assessed. EVALUATION: Patients in this prospective, multicenter trial were undergoing elective, nonendoscopic cardiac operations. A core laboratory independently assessed all intraprocedural and 90-day transesophageal echocardiograms. Sixty patients (37 men), aged 33 to 86 years, enrolled. The mean LAA application time was 27 seconds. Transesophageal echocardiograms at 90 days were available in 54 patients, and no leaks were detected. The residual LAA cavity exceeded 6 mm in 5 patients. One delivery device failed to close, and an adjunctive suture was required to complete LAA exclusion. One patient required adjunct sutures at a small tear site related to manual manipulation after fastener application. CONCLUSIONS: The study demonstrated safety and efficacy of this LAA exclusion device, offering an alternative to manual suturing or staples with or without reinforcement.

Antegrade versus retrograde cerebral protection in repair of acute ascending aortic dissection.

The objective of this study was to compare retrograde with antegrade cerebral protection during acute aortic dissection repair using cerebral oximetry measurements. Fifty consecutive acute ascending aortic dissection repairs were analyzed. Cerebral oximetry data were collected for 41 of 50. Eight patients who had antegrade cerebral protection alone and 29 of 41 had retrograde cerebral protection alone. The per cent change in cerebral oximetry values during deep hypothermic circulatory arrest from baseline and from prearrest values was compared for the two groups using Student t test. The per cent change from baseline for the antegrade patients was: right 13.8 per cent and left -2.5 per cent; the per cent change from baseline for retrograde patients was: right 0.8 per cent and left 0.2 per cent (P values 0.216 and 0.725, respectively). The per cent change from the prearrest value for the antegrade patients was: right -12 per cent and left -15 per cent; the per cent change from prearrest for retrograde patients was: right -15 per cent and left -16 per cent (P values 0.514 and 0.956, respectively). No compelling evidence for an advantage to either antegrade or retrograde cerebral perfusion was detected. Further study with a focus on neurologic outcomes is warranted.