Leaf Anatomy and Ultrastructure of Poa Ligularis After Defoliation and Water Stress

The objective of this study was to determine the effect of defoliation and water stress on leaf anatomy and the mesophyll cell ultrastructure of Poa ligularis. Anatomical differences were detected mainly at epidermal level. Under water stress, leaf roughness was enhanced since the epidermal-cell surface contours became conspicuous. Under defoliation the microscopic roughness decreased as a result of fewer epicuticular wax crystals being formed. Defoliation produced an enhancement of the interlamellar spaces in the irrigated plantís chloroplast. Under no defoliation conditions, chloroplast structure was not affected by water stress. When subjected to water stress, lightly defoliated plants presented chloroplasts with a bellowed outer membrane, irregular thylacoid distribution and the disorganization of peripheral grana. Severely defoliated plants showed disorganized internal chloroplast membranes and even the disappearance of the grana. No breakdown or disappearance of chloroplast external membranes was detected under the imposed growing conditions, suggesting that no irreversible changes were induced

Cardiovascular testing recovery in Latin America one year into the COVID-19 pandemic: An analysis of data from an international longitudinal survey.

The INCAPS COVID Investigators Group, listed by name in the Appendix, thank cardiology and imaging professional societies worldwide for their assistance in disseminating the survey to their memberships. These include alphabetically, but are not limited to, American Society of Nuclear Cardiology, Arab Society of Nuclear Medicine, Australasian Association of Nuclear Medicine Specialists, Australia-New Zealand Society of Nuclear Medicine, Belgian Society of Nuclear Medicine, Brazilian Nuclear Medicine Society, British Society of Cardiovascular Imaging, Conjoint Committee for the Recognition of Training in CT Coronary Angiography Australia and New Zealand, Consortium of Universities and Institutions in Japan, Danish Society of Cardiology, Gruppo Italiano Cardiologia Nucleare, Indonesian Society of Nuclear Medicine, Japanese Society of Nuclear Cardiology, Moscow Regional Department of Russian Nuclear Medicine Society, Philippine Society of Nuclear Medicine, Russian Society of Radiology, Sociedad Española de Medicina Nuclear e Imagen Molecular, Society of Cardiovascular Computed Tomography, and Thailand Society of Nuclear Medicine.Peer reviewe

Standardized research protocols enable transdisciplinary research of climate variation impacts in corn production systems

The important questions about agriculture, climate, and sustainability have become increasingly complex and require a coordinated, multifaceted approach for developing new knowledge and understanding. A multistate, transdisciplinary project was begun in 2011 to study the potential for both mitigation and adaptation of corn-based cropping systems to climate variations. The team is measuring the baseline as well as change of the system\u27s carbon (C), nitrogen (N), and water footprints, crop productivity, and pest pressure in response to existing and novel production practices. Nine states and 11 institutions are participating in the project, necessitating a well thought out approach to coordinating field data collection procedures at 35 research sites. In addition, the collected data must be brought together in a way that can be stored and used by persons not originally involved in the data collection, necessitating robust procedures for linking metadata with the data and clearly delineated rules for use and publication of data from the overall project. In order to improve the ability to compare data across sites and begin to make inferences about soil and cropping system responses to climate across the region, detailed research protocols were developed to standardize the types of measurements taken and the specific details such as depth, time, method, numbers of samples, and minimum data set required from each site. This process required significant time, debate, and commitment of all the investigators involved with field data collection and was also informed by the data needed to run the simulation models and life cycle analyses. Although individual research teams are collecting additional measurements beyond those stated in the standardized protocols, the written protocols are used by the team for the base measurements to be compared across the region. A centralized database was constructed to meet the needs of current researchers on this project as well as for future use for data synthesis and modeling for agricultural, ecosystem, and climate sciences

Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins

Understanding the normal function of the Huntingtin (HTT) protein is of significance in the design and implementation of therapeutic strategies for Huntington's disease (HD). Expansion of the CAG repeat in the HTT gene, encoding an expanded polyglutamine (polyQ) repeat within the HTT protein, causes HD and may compromise HTT's normal activity contributing to HD pathology. Here, we investigated the previously defined role of HTT in autophagy specifically through studying HTT's association with ubiquitin. We find that HTT interacts directly with ubiquitin in vitro. Tandem affinity purification was used to identify ubiquitinated and ubiquitin-associated proteins that copurify with a HTT N-terminal fragment under basal conditions. Copurification is enhanced by HTT polyQ expansion and reduced by mimicking HTT serine 421 phosphorylation. The identified HTT-interacting proteins include RNA-binding proteins (RBPs) involved in mRNA translation, proteins enriched in stress granules, the nuclear proteome, the defective ribosomal products (DRiPs) proteome and the brain-derived autophagosomal proteome. To determine whether the proteins interacting with HTT are autophagic targets, HTT knockout (KO) cells and immunoprecipitation of lysosomes were used to investigate autophagy in the absence of HTT. HTT KO was associated with reduced abundance of mitochondrial proteins in the lysosome, indicating a potential compromise in basal mitophagy, and increased lysosomal abundance of RBPs which may result from compensatory up-regulation of starvation-induced macroautophagy. We suggest HTT is critical for appropriate basal clearance of mitochondrial proteins and RBPs, hence reduced HTT proteostatic function with mutation may contribute to the neuropathology of HD

Molecular Pathological Classification of Colorectal Cancer

Colorectal cancer (CRC) shows variable underlying molecular changes with two major mechanisms of genetic instability: chromosomal instability and microsatellite instability. This review aims to delineate the different pathways of colorectal carcinogenesis and provide an overview of the most recent advances in molecular pathological classification systems for colorectal cancer. Two molecular pathological classification systems for CRC have recently been proposed. Integrated molecular analysis by The Cancer Genome Atlas project is based on a wide-ranging genomic and transcriptomic characterisation study of CRC using array-based and sequencing technologies. This approach classified CRC into two major groups consistent with previous classification systems: (1) ∼16 % hypermutated cancers with either microsatellite instability (MSI) due to defective mismatch repair (∼13 %) or ultramutated cancers with DNA polymerase epsilon proofreading mutations (∼3 %); and (2) ∼84 % non-hypermutated, microsatellite stable (MSS) cancers with a high frequency of DNA somatic copy number alterations, which showed common mutations in APC, TP53, KRAS, SMAD4, and PIK3CA. The recent Consensus Molecular Subtypes (CMS) Consortium analysing CRC expression profiling data from multiple studies described four CMS groups: almost all hypermutated MSI cancers fell into the first category CMS1 (MSI-immune, 14 %) with the remaining MSS cancers subcategorised into three groups of CMS2 (canonical, 37 %), CMS3 (metabolic, 13 %) and CMS4 (mesenchymal, 23 %), with a residual unclassified group (mixed features, 13 %). Although further research is required to validate these two systems, they may be useful for clinical trial designs and future post-surgical adjuvant treatment decisions, particularly for tumours with aggressive features or predicted responsiveness to immune checkpoint blockade

Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group

\ua9 2022 The Authors. Background & Aims: Autoimmune hepatitis (AIH) has been well characterised and codified through the development of diagnostic criteria. These criteria have been adapted and simplified and are widely used in clinical practice. However, there is a need to update and precisely define the criteria for both treatment response and treatment. Methods: A systematic review was performed and a modified Delphi consensus process was used to identify and redefine the response criteria in autoimmune hepatitis. Results: The consensus process initiated by the International Autoimmune Hepatitis Group proposes that the term ‘complete biochemical response’ defined as ‘normalization of serum transaminases and IgG below the upper limit of normal’ be adopted to include a time point at 6 months after initiation of treatment. An insufficient response by 6 months was a failure to meet the above definition. Non-response was defined as ‘<50% decrease of serum transaminases within 4 weeks after initiation of treatment’. Remission is defined as liver histology with a Hepatitis Activity Index <4/18. Intolerance to treatment was agreed to stand for ‘any adverse event possibly related to treatment leading to potential drug discontinuation’. Conclusions: These definitions provide a simple and reproducible framework to define treatment response and non-response, irrespective of the therapeutic intervention. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable inter-study comparisons. Future prospective database studies are needed to validate these endpoints. Lay summary: Consensus among international experts on response criteria and endpoints in autoimmune hepatitis is lacking. A consensus on endpoints is urgently required to set a global standard for the reporting of study results and to enable the comparison of results between clinical trials. Therefore, the International Autoimmune Hepatitis Group (IAIHG) herein presents a statement on 5 agreed response criteria and endpoints: complete biochemical response, insufficient response, non-response, remission, and intolerance to treatment, which can be used to guide future reporting

Which patients benefit from adding short-term psychodynamic psychotherapy to antidepressants in the treatment of depression?: A systematic review and meta-analysis of individual participant data

Multivariate analysis of psychological dat

Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis

\ua9 2024 The Author(s)Background & Aims: In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain. Methods: We conducted an international retrospective cohort study among patients with PBC treated with ursodeoxycholic acid and followed by vibration-controlled transient elastography between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation, or death, was quantified using the hazard ratio and its confidence interval. Results: A total of 6362 LSMs were performed in 3078 patients (2007 on ursodeoxycholic acid alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1000 person-years). LSM progressed in 59% of patients (mean, 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (P < .001). For example, the adjusted hazard ratios (95% confidence interval) associated with a 20% annual variation in LSM were 2.13 (1.89–2.45) for the increase and 0.40 (0.33–0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or liver transplantation was considered. Conclusions: Tracking longitudinal changes in LSM using vibration-controlled transient elastography provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate end point in PBC clinical trials

Prognostic scores for ursodeoxycholic acid-treated patients predict graft loss and mortality in recurrent primary biliary cholangitis after liver transplantation

\ua9 2024 The AuthorsBackground & Aims: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC. Methods: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC was 58.0 years [IQR 53.2–62.6], and 298 patients (90%) were female. The biochemical response was measured with serum levels of alkaline phosphatase (ALP) and bilirubin, and Paris-2, GLOBE and UK-PBC scores at 1 year after UDCA initiation. Results: During a median follow-up of 8.7 years [IQR 4.3–12.9] after rPBC diagnosis, 52 patients (16%) had graft loss and 103 (31%) died. After 1 year of UDCA initiation the histological stage at rPBC (hazard ratio [HR] 3.97, 95% CI 1.36-11.55, p = 0.01), use of prednisone (HR 3.18, 95% CI 1.04-9.73, p = 0.04), ALP xULN (HR 1.59, 95% CI 1.26-2.01, p <0.001), Paris-2 criteria (HR 4.14, 95% CI 1.57-10.92, p = 0.004), GLOBE score (HR 2.82, 95% CI 1.71-4.66, p <0.001), and the UK-PBC score (HR 1.06, 95% CI 1.03-1.09, p <0.001) were associated with graft survival in the multivariate analysis. Similar results were observed for overall survival. Conclusion: Patients with rPBC and disease activity, as indicated by standard PBC risk scores, have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC. Impact and implications: One in three people who undergo liver transplantation for primary biliary cholangitis develop recurrent disease in their new liver. Patients with recurrent primary biliary cholangitis and incomplete response to ursodeoxycholic acid, according to conventional prognostic scores, have worse clinical outcomes, with higher risk of graft loss and mortality in similar ways to the disease before liver transplantation. Our results supportsupport efforts to treat recurrent disease in similar ways to pre-transplant primary biliary cholangitis