Controlling Molecular Photoisomerization in Photonic Cavities through Polariton Funneling.

Strong coupling between photonic modes and molecular electronic excitations, creating hybrid light-matter states called polaritons, is an attractive avenue for controlling chemical reactions. Nevertheless, experimental demonstrations of polariton-modified chemical reactions remain sparse. Here, we demonstrate modified photoisomerization kinetics of merocyanine and diarylethene by coupling the reactant's optical transition with photonic microcavity modes. We leverage broadband Fourier-plane optical microscopy to noninvasively and rapidly monitor photoisomerization within microcavities, enabling systematic investigation of chemical kinetics for different cavity-exciton detunings and photoexcitation conditions. We demonstrate three distinct effects of cavity coupling: first, a renormalization of the photonic density of states, akin to a Purcell effect, leads to enhanced absorption and isomerization rates at certain wavelengths, notably red-shifting the onset of photoisomerization. This effect is present under both strong and weak light-matter couplings. Second, kinetic competition between polariton localization into reactive molecular states and cavity losses leads to a suppression of the photoisomerization yield. Finally, our key result is that in reaction mixtures with multiple reactant isomers, exhibiting partially overlapping optical transitions and distinct isomerization pathways, the cavity resonance can be tuned to funnel photoexcitations into specific reactant isomers. Thus, upon decoherence, polaritons localize into a chosen isomer, selectively triggering the latter's photoisomerization despite initially being delocalized across all isomers. This result suggests that careful tuning of the cavity resonance is a promising avenue to steer chemical reactions and enhance product selectivity in reaction mixtures.

The effectiveness of cognitive behavioural therapy for depression in women with breast cancer: a systematic review and meta-analysis.

BACKGROUND: Depression is a common co-morbidity in women with breast cancer. Previous systematic reviews investigating cognitive behavioural therapy (CBT) for depression in this population based their conclusions on findings from studies with varying and often limited specificity, quality and/or quantity of CBT within their interventions. AIM: To determine the effectiveness of a specific, well-evidenced CBT protocol for depression in women with breast cancer. METHOD: Online databases were systematically searched to identify randomised controlled trials (RCTs) testing CBT (aligned to Beck's protocol) as a treatment for depression in women with breast cancer. Screening, data extraction and risk of bias assessment were independently undertaken by two study authors. Both narrative synthesis and meta-analysis were used to analyse the data. The meta-analysis used a random effects model to compare CBT with non-active/active controls of depression using validated, self-report measures. RESULTS: Six RCTs were included in the narrative synthesis, and five in the meta-analysis (n = 531 participants). Overall, CBT demonstrated an improvement in depression scores in the CBT condition versus active and non-active controls at post-intervention (SMD = -0.93 [95% CI -1.47, -0.40]). Narratively, five out of six RCTs reported statistically significant improvements in depression symptoms for CBT over control conditions for women with breast cancer. CONCLUSION: CBT aligned to Beck's protocol for depression appears effective for treating depression in women with breast cancer. However, further research is needed for women with stage IV breast cancer. The clinical recommendation is that therapists utilise Beck's CBT protocol for depression, whilst considering the complex presentation and adapt their practice accordingly.

Initial outcomes of a dedicated multidisciplinary non-alcoholic fatty liver disease clinic: a retrospective cohort study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a major healthcare burden. Real-world outcomes in dedicated tertiary care settings in Australia remain unknown. AIM: To evaluate the initial outcomes of patients referred to a dedicated multidisciplinary tertiary care NAFLD clinic. METHODS: Retrospective review of all adult patients with NAFLD who attended a dedicated tertiary care NAFLD clinic between January 2018 and February 2020 and who had two clinic visits and FibroScans at least 12 months apart. Demographic and health-related clinical and laboratory data were extracted from electronic medical records. Key outcome measures were serum liver chemistries, liver stiffness measurement (LSM) and weight control at 12 months. RESULTS: A total of 137 patients with NAFLD were included. Median (interquartile range (IQR)) follow-up time was 392 days (343-497 days). One hundred and eleven patients (81%) achieved weight control (i.e. weight loss or stability). Markers of liver disease activity were significantly improved, including median (IQR) serum alanine aminotransferase (48 (33-76) vs 41 (26-60) U/L, P = 0.009) and aspartate aminotransferase (35 (26-54) vs 32 (25-53) U/L, P = 0.020). Median (IQR) LSM across the whole cohort was significantly improved (8.4 (5.3-11.8) vs 7.0 (4.9-10.1) kPa, P = 0.001). No significant reduction was observed in mean body weight or the frequency of metabolic risk factors. CONCLUSIONS: This study highlights a new model of care for patients with NAFLD and demonstrates promising initial outcomes in relation to significant reductions in markers of liver disease severity. Although most patients achieved weight control, further refinements are needed to achieve significant weight reduction including more frequent and structured dietetic and/or pharmacotherapeutic interventions.

Accurate phase detection in time-domain heterodyne SFG spectroscopy.

Heterodyne detection is a ubiquitous tool in spectroscopy for the simultaneous detection of intensity and phase of light. However, the need for phase stability hinders the application of heterodyne detection to electronic spectroscopy. We present an interferometric design for a phase-sensitive electronic sum frequency generation (e-SFG) spectrometer in the time domain with lock-in detection. Our method of continuous phase modulation of one arm of the interferometer affords direct measurement of the phase between SFG and local oscillator fields. Errors in the path length difference caused by drifts in the optics are corrected, offering unprecedented stability. This spectrometer has the added advantage of collinear fundamental beams. The capabilities of the spectrometer are demonstrated with proof-of-principle experiments with GaAs e-SFG spectra, where we see significantly improved signal to noise ratio, spectral accuracy, and lineshapes.

Effector MiSSP7 of the mutualistic fungus Laccaria bicolor stabilizes the Populus JAZ6 protein and represses jasmonic acid (JA) responsive genes.

Ectomycorrhizal fungi, such as Laccaria bicolor, support forest growth and sustainability by providing growth-limiting nutrients to their plant host through a mutualistic symbiotic relationship with host roots. We have previously shown that the effector protein MiSSP7 (Mycorrhiza-induced Small Secreted Protein 7) encoded by L. bicolor is necessary for the establishment of symbiosis with host trees, although the mechanistic reasoning behind this role was unknown. We demonstrate here that MiSSP7 interacts with the host protein PtJAZ6, a negative regulator of jasmonic acid (JA)-induced gene regulation in Populus. As with other characterized JASMONATE ZIM-DOMAIN (JAZ) proteins, PtJAZ6 interacts with PtCOI1 in the presence of the JA mimic coronatine, and PtJAZ6 is degraded in plant tissues after JA treatment. The association between MiSSP7 and PtJAZ6 is able to protect PtJAZ6 from this JA-induced degradation. Furthermore, MiSSP7 is able to block--or mitigate--the impact of JA on L. bicolor colonization of host roots. We show that the loss of MiSSP7 production by L. bicolor can be complemented by transgenically varying the transcription of PtJAZ6 or through inhibition of JA-induced gene regulation. We conclude that L. bicolor, in contrast to arbuscular mycorrhizal fungi and biotrophic pathogens, promotes mutualism by blocking JA action through the interaction of MiSSP7 with PtJAZ6.

Revolution in diet therapy for inflammatory bowel disease.

Until recently, diet as a therapeutic tool to treat inflammatory bowel disease (IBD) has not been proven effective. Nearly a century in the making we are in the grips of a revolution in diet therapies for IBD, driven by emerging data revealing diet as a key environmental factor associated with IBD susceptibility, and observational studies suggesting that dietary intake may play a role in the disease course of established IBD. This review summarizes the current evidence for diets trialed as induction and maintenance therapy for IBD. For Crohn's disease, exclusive enteral nutrition and the Crohn's disease exclusion diet with partial enteral nutrition are supported by emerging high-quality evidence as induction therapy, but are short-term approaches that are not feasible for prolonged use. Data on diet as maintenance therapy for Crohn's disease are conflicting, with some studies supporting fortification, and others suppression, of certain food components. For ulcerative colitis, data are not as robust for diet as induction and maintenance therapy; however, consistent themes are emerging, suggesting benefits for diets that are plant-based, high in fiber and low in animal protein. Further studies for both Crohn's disease and ulcerative colitis are eagerly awaited, which will allow specific recommendations to be made. Until this time, recommendations default to population based healthy eating guidelines.

Review article: Mechanisms underlying the effectiveness of exclusive enteral nutrition in Crohn's disease.

BACKGROUND: Exclusive enteral nutrition (EEN) induces remission and mucosal healing in patients with Crohn's disease, but the mechanism of action remains unknown. AIM: To outline current understanding of the mechanisms of action of EEN. METHODS: From a comprehensive literature search, published data were critically examined in a narrative review. RESULTS: Multiple potential mechanisms of action have been identified. EEN optimises nutritional status. Differences in gut microbiota in terms of overall diversity and taxonomic community structure are observed between responders and non-responders to EEN. Therapy with EEN alters microbial metabolites (including faecal short-chain fatty acids, amino acids, branched-chain amino acids and sulphide) and faecal pH. Epithelial effects and restoration of barrier function, as well as changes in mucosal cytokine profiles and T-cell subsets are observed in responders to EEN. The impact of inclusion or exclusion of specific dietary components may be of importance, but putative detrimental components are found in many formulas. A major challenge in interpreting these findings is that they often contradict or change in opposite directions to what is considered 'beneficial'. It is difficult to differentiate between the observations following EEN being driven by EEN per se and those associated with resolving inflammation. CONCLUSIONS: The mechanisms of action of EEN are likely to involve a complex interplay between host mucosal immune response and luminal environment, but the identity of key factors remains poorly understood. A better definition of pathogenic factors may aid in developing more targeted dietary treatment and provide insights into the pathogenesis of Crohn's disease.

Lessons from an audit of exclusive enteral nutrition in adult inpatients and outpatients with active Crohn's disease: a single-centre experience.

Objective: To evaluate clinical outcomes, patterns of use, tolerance and nutritional outcomes of exclusive enteral nutrition (EEN) in adults with Crohn's disease and to compare initiation in the inpatient compared with ambulatory care setting. Design/method: Adults with Crohn's disease who received EEN at a single centre over 2.5 years were identified and outcomes assessed via examination of patient records. Results: EEN was initiated in 60 patients (23 as an outpatient) who had objective evidence of active disease. Of 49 in whom the goal was induction of remission, 28 completed EEN and 24 achieved clinical remission/response. Twenty-one withdrew prematurely, due to intolerance in 15 and disease factors in 6. Of 11 with a planned intervention, 6 fulfilled the goal of downstaging disease while two were intolerant. Completion of the prescribed therapy was associated with self-reported adherence to EEN and with improvements in disease activity scores and biochemical markers. Malnutrition halved (40% to 20%) and intentional weight loss (median 5.1 kg) was achieved in six obese patients. The major reason for intolerance was the inability to accept total avoidance of non-formula food. There were no differences in any outcomes according to the location of initiation of therapy. Conclusion: Positive outcomes occur in 70% of adult patients with Crohn's disease tolerating EEN and 81% in those who are able to completely adhere to EEN, without compromise of nutritional status. Similar success occurs when initiated as an inpatient or outpatient. Failure to tolerate EEN is the major hurdle to its use.

Pseudomonas fluorescens induces strain-dependent and strain-independent host plant responses in defense networks, primary metabolism, photosynthesis, and fitness.

Colonization of plants by nonpathogenic Pseudomonas fluorescens strains can confer enhanced defense capacity against a broad spectrum of pathogens. Few studies, however, have linked defense pathway regulation to primary metabolism and physiology. In this study, physiological data, metabolites, and transcript profiles are integrated to elucidate how molecular networks initiated at the root-microbe interface influence shoot metabolism and whole-plant performance. Experiments with Arabidopsis thaliana were performed using the newly identified P. fluorescens GM30 or P. fluorescens Pf-5 strains. Co-expression networks indicated that Pf-5 and GM30 induced a subnetwork specific to roots enriched for genes participating in RNA regulation, protein degradation, and hormonal metabolism. In contrast, only GM30 induced a subnetwork enriched for calcium signaling, sugar and nutrient signaling, and auxin metabolism, suggesting strain dependence in network architecture. In addition, one subnetwork present in shoots was enriched for genes in secondary metabolism, photosynthetic light reactions, and hormone metabolism. Metabolite analysis indicated that this network initiated changes in carbohydrate and amino acid metabolism. Consistent with this, we observed strain-specific responses in tryptophan and phenylalanine abundance. Both strains reduced host plant carbon gain and fitness, yet provided a clear fitness benefit when plants were challenged with the pathogen P. syringae DC3000.

Dietary management of adults with IBD - the emerging role of dietary therapy.

Historically, dietitians played a minor part in the management of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Patients were commonly referred for consequences of uncontrolled disease, such as malnutrition and bowel obstruction risk. Today, dietitians are fundamental members of the multidisciplinary IBD team, from educating on the role of diet at diagnosis and throughout the lifespan of a patient with IBD to guiding primary induction therapy. This aspect is reflected in published guidelines for IBD management, which previously placed diet as only a minor factor, but now have diet-specific publications. This Review describes a four-step approach in a dietitian's assessment and management of diet in patients with IBD: (1) identifying and correcting nutritional gaps and dietary imbalances; (2) considering diet to treat active disease with the use of exclusive enteral nutrition (EEN) or emerging diets that could replace EEN; (3) using therapeutic diets to control existing complications of IBD, such as reduced fibre to prevent bowel obstruction in stricturing disease or a fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet to manage co-existing functional gut symptoms; and (4) considering the role of diet in preventing IBD development in high-risk populations.

Casein kinases are required for the stability of the glucose-sensing receptor Rgt2 in yeast.

In yeast, glucose induction of HXT (glucose transporter gene) expression is achieved via the Rgt2 and Snf3 glucose sensing receptor (GSR)-mediated signal transduction pathway. The membrane-associated casein kinases Yck1 and Yck2 (Ycks) are involved in this pathway, but their exact role remains unclear. Previous work suggests that the Ycks are activated by the glucose-bound GSRs and transmit the glucose signal from the plasma membrane to the nucleus. However, here we provide evidence that the YCks are constitutively active and required for the stability of the Rgt2 receptor. Cell surface levels of Rgt2 are significantly decreased in a yck1Δyck2ts mutant, but this is not due to endocytosis-mediated vacuolar degradation of the receptor. Similar observations are made in an akr1Δ mutant, where the Ycks are no longer associated with the membrane, and in a sod1Δ mutant in which the kinases are unstable. Of note, in an akr1Δ mutant, both the Ycks and Rgt2 are mislocalized to the cytoplasm, where Rgt2 is stable and functions as an effective receptor for glucose signaling. We also demonstrate that Rgt2 is phosphorylated on the putative Yck consensus phosphorylation sites in its C-terminal domain (CTD) in a Yck-dependent manner and that this glucose-induced modification is critical for its stability and function. Thus, these results indicate a role for the Ycks in stabilizing Rgt2 and suggest that Rgt2 may use glucose binding as a molecular switch not to activate the Ycks but to promote Yck-dependent interaction and phosphorylation of the CTD that increases its stability.

Exclusive enteral nutrition: An optimal care pathway for use in adult patients with active Crohn's disease.

BACKGROUND AND AIM: Exclusive enteral nutrition (EEN) is progressively being used as a therapeutic option for adults with Crohn's Disease (CD); however, there is no standardized approach to delivering this therapy. The aim of this study is to develop an optimal care pathway for using EEN in adults with CD. This will create a standard of care that can be used as a benchmark practice and will provide direction for future research. METHODS: A working group of 12 multidisciplinary inflammatory bowel disease specialists across Australia and New Zealand was convened to develop a practical, clinically focused care pathway for using EEN in adults with active CD. Six key areas were identified as part of the care pathway: clinical indications, nutrition assessment, EEN protocol, monitoring, accessing formula, and food reintroduction. Current literature was identified via systematic review, and quality of evidence was graded. Consensus expert opinion was used where literature gaps were identified. RESULTS: An optimal care pathway for using EEN in adults with CD was developed with six key consensus statements on how to use EEN in adults with active CD. These key statements identify clinical indications for use, nutrition assessment, enteral prescription and duration of therapy, monitoring criteria, food reintroduction, and the role of partial EEN. An accompanying patient resource was also developed. CONCLUSION: EEN is recommended as a treatment option to induce remission in adults with active CD. The consensus statements developed are practical and are based on best available evidence and expert opinion to assist in developing a standardized approach to delivering EEN therapy.

Reliability of clinician-based (GRBAS and CAPE-V) and patient-based (V-RQOL and IPVI) documentation of voice disorders.

This study examined the reliability of two methods for documenting voice quality by clinicians and compared the methods for documenting patients' perceptions of voice quality. It involved a prospective reliability study and a retrospective chart review. Reliability of two clinician-based voice assessment protocols-Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS) and Consensus Auditory Perceptual Evaluation-Voice (CAPE-V)-was evaluated. These two protocols were then compared after use in voice assessments of 42 males and 61 females performed by a certified speech-language pathologist specializing in the assessment of voice disorders. In addition, two patient-based scales (Voice Related Quality of Life, or V-RQOL, and Iowa Patient's Voice Index, or IPVI) obtained from the same patients were compared with each other and with the clinician-based scales. Reliability of clinicians' ratings of overall severity of dysphonia using GRBAS and CAPE-V scales was very good (r>0.80). Agreement between V-RQOL Total scores and IPVI ratings of the patient's perceptions of impact of dysphonia was less strong (Spearman's r=-0.76). There was relatively weak agreement between patient-based and clinician-based scales. Clinician's perceptions of dysphonia appeared to be reliable and unaffected by rating tool, as indicated by the high level of agreement between the two rating systems when they were used together. The CAPE-V system appeared to be more sensitive to small differences within and among patients than the GRBAS system. The V-RQOL and IPVI approaches to documenting patient's perceptions of dysphonia agreed less well possibly due to differences in patient dependence on voice and on interpretation of the rating tool items. The differences between clinician-based and patient-based data support the conclusion that clinicians and patients experience and consider dysphonia very differently.

Eszopiclone for insomnia.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy data, and adverse effects of eszopiclone in the treatment of transient and chronic insomnia in adult and geriatric patients. DATA SOURCES: A MEDLINE literature search (1966-May 2005) was conducted to retrieve articles and abstracts involving eszopiclone. The manufacturer of the drug provided a general summary of clinical data and abstracts of unpublished Phase III clinical trials. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were reviewed, and information deemed relevant was included for this review. DATA SYNTHESIS: Food and Drug Administration approval of eszopiclone was based on 6 double-blind, placebo-controlled trials. Five trials published in abstract or study form were reviewed. The sixth trial was not available for evaluation. An open-label continuation trial was also reviewed. All studies showed statistically significant improvements in sleep parameters in adult and elderly patients treated for insomnia with eszopiclone. CONCLUSIONS: The results of the 5 available double-blind, placebo-controlled studies (and 1 open-label, 6-month extension) showed that eszopiclone was safe and effective in the treatment of transient and chronic insomnia in adult and geriatric patients. Tolerance with long-term exposure (6 mo) and rebound insomnia were not observed. The results of the 6-month, open-label extension trial demonstrated that improvements in sleep parameters were sustained. Future studies comparing eszopiclone with other non benzodiazepine sedative-hypnotics (eg, zolpidem, zaleplon) are needed with cost data to clearly define the role of eszopiclone in the pharmacotherapy of chronic insomnia.