INPP4B overexpression and c-KIT downregulation in human achalasia.

BACKGROUND: Achalasia is a rare motility disorder characterized by myenteric neuron and interstitial cells of Cajal (ICC) abnormalities leading to deranged/absent peristalsis and lack of relaxation of the lower esophageal sphincter. The mechanisms contributing to neuronal and ICC changes in achalasia are only partially understood. Our goal was to identify novel molecular features occurring in patients with primary achalasia. METHODS: Esophageal full-thickness biopsies from 42 (22 females; age range: 16-82 years) clinically, radiologically, and manometrically characterized patients with primary achalasia were examined and compared to those obtained from 10 subjects (controls) undergoing surgery for uncomplicated esophageal cancer (or upper stomach disorders). Tissue RNA extracted from biopsies of cases and controls was used for library preparation and sequencing. Data analysis was performed with the "edgeR" option of R-Bioconductor. Data were validated by real-time RT-PCR, western blotting and immunohistochemistry. KEY RESULTS: Quantitative transcriptome evaluation and cluster analysis revealed 111 differentially expressed genes, with a P 64 10-3 . Nine genes with a P 64 10-4 were further validated. CYR61, CTGF, c-KIT, DUSP5, EGR1 were downregulated, whereas AKAP6 and INPP4B were upregulated in patients vs controls. Compared to controls, immunohistochemical analysis revealed a clear increase in INPP4B, whereas c-KIT immunolabeling resulted downregulated. As INPP4B regulates Akt pathway, we used western blot to show that phospho-Akt was significantly reduced in achalasia patients vs controls. CONCLUSIONS & INFERENCES: The identification of altered gene expression, including INPP4B, a regulator of the Akt pathway, highlights novel signaling pathways involved in the neuronal and ICC changes underlying primary achalasia

The postmastectomy pain syndrome: an epidemiological study on the prevalence of chronic pain after surgery for breast cancer

The prevalence of the postmastectomy pain syndrome (PMPS) and its clinical characteristics was assessed in a group of patients who had undergone surgery for breast cancer at the Department of Surgery, Odense University Hospital, within the period of 1 May 2003 to 30 April 2004. The study included 258 patients and a reference group of 774 women. A questionnaire was mailed to the patients 1½ year after surgery and to the women in the reference group. The PMPS was defined as pain located in the area of the surgery or ipsilateral arm, present at least 4 days per week and with an average intensity of at least 3 on a numeric rating scale from 0 to 10. The prevalence of PMPS was found to be 23.9%. The odds ratio of developing PMPS was 2.88 (95% confidence interval 1.84–4.51). Significant risk factors were as follows: having undergone breast surgery earlier (OR 8.12), tumour located in the upper lateral quarter (OR 6.48) and young age (OR 1.04). This study shows that, although recent advances in the diagnostic and surgical procedures have reduced the frequency of the more invasive surgical procedures, there still is a considerable risk of developing PMPS after treatment of breast cancer

Challenges in assessing and managing multi-hazard risks: A European stakeholders perspective

The latest evidence suggests that multi-hazards and their interrelationships (e.g., triggering, compound, and consecutive hazards) are becoming more frequent across Europe, underlying a need for resilience building by moving from single-hazard-focused to multi-hazard risk assessment and management. Although significant advancements were made in our understanding of these events, mainstream practice is still focused on risks due to single hazards (e.g., flooding, earthquakes, droughts), with a limited understanding of the stakeholder needs on the ground. To overcome this limitation, this paper sets out to understand the challenges for moving towards multi-hazard risk management through the perspective of European stakeholders. Based on five workshops across different European pilots (Danube Region, Veneto Region, Scandinavia, North Sea, and Canary Islands) and an expert workshop, we identify five prime challenges: i) governance, ii) knowledge of multi-hazards and multi-risks, iii) existing approaches to disaster risk management, iv) translation of science to policy and practice, and v) lack of data. These challenges are inherently linked and cannot be tackled in isolation with path dependency posing a significant hurdle in transitioning from single- to multi-hazard risk management. Going forward, we identify promising approaches for overcoming some of the challenges, including emerging approaches for multi-hazard characterisation, a common understanding of terminology, and a comprehensive framework for guiding multi-hazard risk assessment and management. We argue for a need to think beyond natural hazards and include other threats in creating a comprehensive overview of multi-hazard risks, as well as promoting thinking of multi-hazard risk reduction in the context of larger development goals

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study

Background Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours.Methods In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186.Findings Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78 center dot 6%] female patients and 4922 [21 center dot 4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1 center dot 4 [IQR 0 center dot 6-3 center dot 4]) compared with the prepandemic phase (2 center dot 0 [0 center dot 9-3 center dot 7]; p<0 center dot 0001) and pandemic decrease phase (2 center dot 3 [1 center dot 0-5 center dot 0]; p<0 center dot 0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69 center dot 0%] of 3704 vs 1515 [71 center dot 5%] of 2119; OR 1 center dot 1 [95% CI 1 center dot 0-1 center dot 3]; p=0 center dot 042), lymph node metastases (343 [9 center dot 3%] vs 264 [12 center dot 5%]; OR 1 center dot 4 [1 center dot 2-1 center dot 7]; p=0 center dot 0001), and tumours at high risk of structural disease recurrence (203 [5 center dot 7%] of 3584 vs 155 [7 center dot 7%] of 2006; OR 1 center dot 4 [1 center dot 1-1 center dot 7]; p=0 center dot 0039).Interpretation Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation.Funding None.Copyright (c) 2023 Published by Elsevier Ltd. All rights reserved

Climate Change Challenge (3C) and Social-Economic-Ecological Interface-Building—Exploring Potential Adaptation Strategies for Bio-resource Conservation and Livelihood Development: Epilogue

Climate change is arguably the single most dominant environmental threat facing humanity. Its manifestations, particularly through rising temperatures, changing rainfall, sea-level rise and increasing droughts and floods have the potential to adversely impact natural ecosystems (such as forests, grasslands, rivers and oceans) and socioeconomic systems (such as food production, fisheries and coastal settlements). This is adding additional stresses to the ecosystem services which form a substantial source of income to the rural inhabitants. It is most proximate and inextricably linked to well-being, development and economic growth which are part of the eight Millennium Development Goals (MDGs), which ran from 2000 to 2015

Aboveground biomass density models for NASA's Global Ecosystem Dynamics Investigation (GEDI) lidar mission

NASA's Global Ecosystem Dynamics Investigation (GEDI) is collecting spaceborne full waveform lidar data with a primary science goal of producing accurate estimates of forest aboveground biomass density (AGBD). This paper presents the development of the models used to create GEDI's footprint-level (similar to 25 m) AGBD (GEDI04_A) product, including a description of the datasets used and the procedure for final model selection. The data used to fit our models are from a compilation of globally distributed spatially and temporally coincident field and airborne lidar datasets, whereby we simulated GEDI-like waveforms from airborne lidar to build a calibration database. We used this database to expand the geographic extent of past waveform lidar studies, and divided the globe into four broad strata by Plant Functional Type (PFT) and six geographic regions. GEDI's waveform-to-biomass models take the form of parametric Ordinary Least Squares (OLS) models with simulated Relative Height (RH) metrics as predictor variables. From an exhaustive set of candidate models, we selected the best input predictor variables, and data transformations for each geographic stratum in the GEDI domain to produce a set of comprehensive predictive footprint-level models. We found that model selection frequently favored combinations of RH metrics at the 98th, 90th, 50th, and 10th height above ground-level percentiles (RH98, RH90, RH50, and RH10, respectively), but that inclusion of lower RH metrics (e.g. RH10) did not markedly improve model performance. Second, forced inclusion of RH98 in all models was important and did not degrade model performance, and the best performing models were parsimonious, typically having only 1-3 predictors. Third, stratification by geographic domain (PFT, geographic region) improved model performance in comparison to global models without stratification. Fourth, for the vast majority of strata, the best performing models were fit using square root transformation of field AGBD and/or height metrics. There was considerable variability in model performance across geographic strata, and areas with sparse training data and/or high AGBD values had the poorest performance. These models are used to produce global predictions of AGBD, but will be improved in the future as more and better training data become available