Dear Editor in ChiefWe read with interest “The outcome of pregnancy in women with cystic fibrosis: a UK population based descriptive study1.”  We thank the authors for this timely paper which highlights the growing need for robust clinical data capture for Cystic Fibrosis maternal and infant health.This is a rapidly expanding area of interest as the landscape of CF care is changing dramatically, particularly in the era of CFTR modulation. Clinical teams caring for people living with CF are increasingly being asked about pregnancy and potential risks to mothers and their babies. As the authors highlight data on pregnancy in CF historically has mainly been small case series from single sites carried out before CFTR modulators were widely available. The guidelines referenced are somewhat dated as the authors allude to.The authors describe the strength of the data collection in the form of the UK OSS. However, over the 24 month period only 71 cases are collected. The authors also reference around 30 -40 women with CF being pregnant per year in the UK.* We suspect that there are a significant proportion of missing cases within this study suggested by an interrogation of the UK CF Registry data. The UK CF Registry has been sponsored and hosted by the CF Trust since 2007. CF clinical care teams enter data at every specialist centre and clinic across the UK, with over 99% of people with CF consenting to their data being submitted. Data from the UK CF Registry over the time period reported by this study revealed 64, 71 and 58 women having babies in 2015, 2016 and 2017 respectively. Although it is not possible to exactly match the dates (March 2015 to February 2017) described within this study to the CF registry data it is likely that there were considerably more than 71 cases in a two year period. **There remain queries regarding the clinical details of those women reported in this study. Eight of the 71 (11%) had no underlying CFTR mutation available and 51% were reported as pancreatic sufficient which is much higher than would be expected from a cohort of adults with CF in the UK. For 15 of the women included in the case series, lung function is not described.One of the main conclusions of the paper is that gestational age is highly correlated with FEV1. We find the presentation of this misleading as this is most likely the case because women with poorer lung function had pre-term caesareans or had labour induced earlier. Although this doesn’t change the correlation it may mean that it is due to the intervention.There is an ongoing UK Government funded project, CF Prosper, looking at pregnancies in women with CF using UK CF Registry and US CF Foundation registry data from 2003 to current (https://cfprosper.yolasite.com). We expect to be able to report on over 1000 pregnancies and help to delineate predictive factors for successful pregnancies and examine subsequent maternal disease trajectory after starting a family. Using the largest dataset yet available we also hope to develop a decision-making tool in conjunction with women living with CF and their clinical care teams to enable women with CF to make more informed choices regarding pregnancy and starting a family.Yours faithfully,Jamie Duckers, Cardiff and Vale University Health Board, UKDaniela Schlueter, Liverpool University, UKRhiannon Phillips, Cardiff Metropolitan University, UKRebecca Cosgriff, Cystic Fibrosis Trust, UKEsan Oluwaseun, Liverpool University, UKShantini Paranjothy, Aberdeen University, UKDeni Williams, Cardiff Metropolitan University, UKRachel Norman Cardiff and Vale University Health Board, UKDavid Taylor Robinson, Liverpool University, UKSiobhan Carr, Royal Brompton Hospital, London UK1) Ashcroft A, Chapman SJ, Mackillop L. The outcome of pregnancy in women with cystic fibrosis: a UK population-based descriptive study. BJOG. 2020 Jul 19. doi: 10.1111/1471-0528.16423. Epub ahead of print. PMID: 32683738.*There appears to be an error in the referencing numbering within the article as no reference 13 exists**Details on how to request data from the UK CF Registry are available via www.cysticfibrosis.org.uk/registry

MYH9 disorder is characterized by macrothrombocytopenia with or without granulocyte DÖhle body-like inclusion bodies. Diagnosis is made by immunofluorescence analysis and genetic study of the MYH9 gene. Our collaborative study between Thailand and Japan began with 67 Thai patients with macrothrombocytopenia. Of these, 11 patients(16.4%), aged 4 months-22 years with platelet counts ranging from 2,000-99,000/uL were diagnosed with MYH9 disorder. MYH9 gene mutations occurred in exons 1,16,30,38,40. One novel mutation was identified (c.4338T>C, p.F1446A). The results indicate that patients with macrothrombocytopenia should be tested for MYH9 disorder in order to avoid misdiagnosis to the other diseases, such as chronic immune thrombocytopenia.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergic disorder with a well-characterised clinical phenotype, but limited understanding of factors associated with food cross-reactivity, severity and tolerance. Methods: A retrospective cohort study spanning 20 years on children with acute FPIES from a single paediatric tertiary centre in New South Wales, Australia focusing on identifying food trigger co-associations and factors associated with reaction severity, multiple trigger FPIES and/or tolerance was performed. Results: 169 individuals with 329 recorded FPIES episodes between 1997 and 2017 were included. 49% were male. The median age at first FPIES reaction was 5 months and median age at diagnosis was 9 months. 73% experienced at least one severe FPIES reaction. Rice (45%), cow’s milk (30%), soy (13%) were the most common triggers. FPIES to rice or cow’s milk were strongly associated with increased odds of having multiple trigger FPIES. Associations between causative foods were seen with rice/oats, cow’s milk/soy, and fish/shellfish. No factors were associated with increased risk of severe reactions. Infants with rice and grains FPIES outgrew their reactions at an earlier age, compared to those with fish FPIES. Conclusions: Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergic disorder with a well-characterised clinical phenotype, but limited understanding of factors associated with food cross-reactivity, severity and tolerance. Methods: A retrospective cohort study spanning 20 years on children with acute FPIES from a single paediatric tertiary centre in New South Wales, Australia focusing on identifying food trigger co-associations and factors associated with reaction severity, multiple trigger FPIES and/or tolerance was performed. Results: 169 individuals with 329 recorded FPIES episodes between 1997 and 2017 were included. 49% were male. The median age at first FPIES reaction was 5 months and median age at diagnosis was 9 months. 73% experienced at least one severe FPIES reaction. Rice (45%), cow’s milk (30%), soy (13%) were the most common triggers. FPIES to rice or cow’s milk were strongly associated with increased odds of having multiple trigger FPIES. The odds of having multiple food FPIES and severe reactions were slightly decreased with vaginal delivery. No factors were associated with increased risk of severe reactions. Infants with rice and grains FPIES outgrew their reactions at an earlier age, compared to those with fish FPIES. Conclusions: Rice remains the most common trigger for FPIES in this region with co-associations between rice/oats and cow’s milk/soy observed. The co-associations among food groups suggest that taxonomically related foods share similar protein structure and trigger similar mechanisms of antigen recognition. Vaginal delivery appears to have a mild protective effect on the development of multiple FPIES and severe reactions.

Certain patients with inborn errors of immunity have defects in DNA damage response, predisposing them to malignancy. Subsequent cancer therapy may require substantial attenuation given defective DNA repair; however, this carries risk of incomplete disease control. We describe a 5-year-old boy with peripheral T-Cell lymphoma with ataxia-telangiectasia (A-T). After incomplete chemotherapeutic response, he underwent allogenic hematopoietic cell transplantation (allo-HCT) with an attenuated preparative regimen, but developed graft rejection and relapse. Following remission with salvage chemotherapy, second allo-HCT with reduced intensity conditioning (RIC) resulted in minimal toxicity and short-term disease control. HCT with RIC can be considered in patients with A-T.

A mathematical model is used to study the effect of the magnetic field on the temporary free convection flow of the electrically conductive fluid past the vertical plate under periodic temperature. The governing momentum and energy equations are solved analytically using the homotopy perturbation method. An approximate analytical solution using Homotopy perturbation method and Laplace transform is carried out for temperature profile in case of constant plate temperature. The results are obtained the analytical and limiting case results ones, and a good agreement is achieved. The effect of different physical parameters on transient velocity and temperature, such as Grashof number, magnetic parameter, Prandtl number and temperature frequency, is examined. Also, the local Skin-friction and local Nusselt number coefficients are obtained and analyzed.

Background: Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define the better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissue sarcoma Study Group (EpSSG) and Children’s Oncology Group (COG). Methods: We retrospectively identified patients with ARMS N1 enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in RMS2005 comprised IVADo (ifosfamide, vincristine, dactinomycin, doxorubicin), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531 it consisted on either VAC (vincristine, dactinomycin, cyclophosphamide) or VAC alternating with VI (vincristine, irinotecan). Local treatment was similar in both protocols. Results: The analysis of the clinical characteristics of 239 patients showed some differences between study groups: in RMS2005, advanced IRS Group and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49% (95%CI=39-59) and 44% (95%CI=30-58), and overall survival (OS), 51% (95%CI=41-61) and 53.6% (95%CI=40-68), in RMS2005 and ARST0531, respectively. In RMS2005, EFS of patients with FOXO1-positive tumors was significantly inferior to those FOXO1-negative (49.3% vs 73%, p=0.034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those FOXO1-negative. Conclusions: The outcome of patients with ARMS N1 was similar using different schemas of chemotherapy. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that this subgroup may benefit from the EpSSG strategy which included maintenance chemotherapy.

Hand and foot syndrome (HFS) is a toxic dermatologic reaction to chemotherapy, commonly described with capecitabine, 5fluouracile, vinorelbine, and cytarabine. Taxanes are less likely to induce HFS, and very few cases reported paclitaxel-induced HFS. We report a serious case of HFS induced by paclitaxel in a breast cancer female.

Background and Purpose: Coronavirus disease (COVID-19) has resulted in high mortality worldwide. However, information regarding cardiac markers for precise risk-stratification is limited. We aimed to discover a sensitive and reliable early-warning biomarker for optimizing management and improving COVID-19 patients’ prognosis. Experiments Approach: This retrospectively single-center case series was conducted between February 4 and April 10, 2020. 3,046 consecutive COVID-19 patients who were receiving treatment at Wuhan Huoshenshan Hospital in China were included. Serum levels of cardiac markers and coronary artery disease (CAD) diagnosis were collected after admission. Single-cell RNA-sequencing was performed to analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor expression. Key Results: Median patient age was 60 years; 1,461 (49.5%) were female, and 1,515 (51.3%) were in a severe/critical condition. Compared to mild/moderate patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. Among severe/critical COVID-19 patients, those with abnormal serum levels of brain natriuretic peptide had a significantly higher mortality than patients with normal levels. Severe/critical COVID-19 patients with pre-existing CAD (165/1,515) had more cases of abnormal brain natriuretic peptide levels than those without CAD. Enhanced SARS-CoV-2 receptor expression was observed in patients with CAD. Regression analysis revealed patients with elevated brain natriuretic peptide were at a higher risk of death. Conclusion and Implications: Brain natriuretic peptide is an effective biomarker for early risk assessment in COVID-19 patients with or without pre-existing CAD. Monitoring BNP status will improve the risk-stratification management and prognosis of patients within one week after admission.

Background: Mediastinal cystic teratoma is a rare diagnosis in adolescence from low-income setting. Pleural effusion often mislead to infection and delay resection. We report a case from high burden tuberculosis country and analyze data from the literature. Methods: Clinical record of an adolescent patient from the Democratic Republic of Congo

Background: Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) is a progressive autosomal recessive disorder characterized by cachexia, gastrointestinal (GI) dysmotility, ptosis, peripheral neuropathy and brain MRI white matter changes. Bi-allelic TYMP mutations lead to deficient thymidine phosphorylase (TP) activity, toxic accumulation of plasma nucleosides (thymidine and deoxyuridine), nucleotide pool imbalances and mtDNA instability. Death is mainly due to GI complications: intestinal perforation, peritonitis, and/or liver failure. Based on our previous observations in 3 patients with MNGIE, that platelet infusions resulted in a transient 40% reduction of plasma nucleoside levels, in 2005 we performed the first HSCT worldwide as a life-long source of TP in a patient with MNGIE. Procedure: HSCT was performed in a total of six patients with MNGIE. The multiple factors involved in the prognosis of this cohort were analyzed and compared to the literature experience. Results: Cell source was bone marrow in five patients and peripheral stem cells in one, all from fully HLA-matched related donors, including four who were TYMP mutation carriers. Four of six (66%) survived compared to the 37% survival rate in the literature. Reduced intensity conditioning regimen contributed to secondary graft failure in 2 patients. 15 years post-HSCT the first transplanted patient is seemingly cured. Severe GI symptoms pre-transplantation were mostly irreversible and a poor prognostic factor. Conclusions: Allogenic HSCT could constitute a curative therapeutic option for carefully selected, young, pre-symptomatic or mildly affected patients. Timing, donor selection and optimal conditioning protocol are major determinants of outcome. HSCT is inadvisable in patients with advanced MNGIE disease.

We also aimed to present our experience about the diagnosis and treatment of our cesarean scar choriocarcinoma case whose tumor was chemoresistant and recurred in four months.

Localised soft tissue swelling as initial presentation in child acute lymphoblastic leukemia (ALL) is extremely rare. We first report one case presenting with clitoris swellings. She was done for an abdominal biopsy from the retroperitoneal mass suspicious of neuroblastoma. Follow-up, she was eventually diagnosed with precursor B cell ALL by bone marrow biopsy, with TCF3-PBX1 fusion gene and additional chromosomal aberrations. After chemotherapy, although the girl had transiently clinical remission, the bone marrow aspirate indicated a poor outcome. Thus, this highly localised presentation is unusual and would hopefully inform clinicians to have a high index of suspicion for ALL.

1.7% of myeloproliferative neoplasms are associated with autoimmune conditions. Association of myasthenia gravis (MG) with chronic myeloid leukemia is reported, but its association with polycythemia vera (PV) has never been reported. We report two patients who had MG and PV with JAK2V617F mutation. Both had splenomegaly but no thymoma.

Understanding how eco-evolutionary processes and environmental factors drive population differentiation and adaptation are key challenges in evolutionary biology and of relevance for biodiversity protection. Differentiation requires at least partial reproductive separation, which may result from geographic isolation (allopatry), isolation by distance (IBD), environment (IBE), adaptation (IBA), and time (IBT). We investigate how ecological and evolutionary processes influence genetic diversity and structure in 11 populations of pike (Esox lucius) using Restriction-site Associated DNA sequencing (RADseq). Study populations represented three ecotypes (freshwater, anadromous, and brackish water resident) along a latitudinal gradient (54.9 - 63.6 °N). Genetic diversity and structure were investigated both for the full RADseq dataset (5993 loci) and for an adaptive subset consisting outlier loci. Both neutral and adaptive processes influenced genetic structure, and their contributions differed between allopatric and sympatric populations, and also within and among ecotypes. Signatures of neutral processes were pronounced among geographically isolated freshwater populations, likely reflecting long time since divergence combined with low gene flow. For sympatric populations, ecotype (anadromous versus resident) and geography influenced both neutral and adaptive genetic structure, consistent with IBE. Outlier analyses pointed to a role of selection associated with salinity and temperature, consistent with IBA. Results provide rare evidence that separate analyses of neutral and adaptive loci can help illuminate how different, potentially interacting, processes jointly contribute to shaping spatiotemporal patterns of biodiversity. It is argued that data on adaptive rather than neutral genetic variation should inform management and policy development.

In this study, the effect of PT with Trichoderma sp. AH on structure of rice wheat (RS) and wheat straw (WS) was investigated. TG/DTG analysis shows that PT could incompletely degrade RS and WS with no significant effect on their group composition. XRD analysis shows that PT could incompletely destroy the crystal structure of RS and WS causing lower crystallinity, which clearly suggests that PT is effective in disrupting the structure. The effect of PT on RS and WS is primarily on cellulose and hemicelluloses decrystallization to amorphous material. XPS analysis shows that PT has some influence on the oxygen- and nitrogen-containing compounds with increasing the relative contents of some oxygen- and nitrogen-containing compounds. PT is an effective preparation for biomass liquefaction by destroying the structure of biomass with minimal loss of carbohydrates.

A document by Qiaoxing Liang. Click on the document to view its contents.

Prosthetic valve endocarditis is a rare but serious complication of cardiac valve replacement, and echocardiography plays a fundamental role in its diagnosis and management. However, there is not much information about the use of the 3D transillumination rendering in this context. In this report we present an unusual case of prosthetic valve endocarditis that exemplifies the utility of this new tool.

Photo-enzymatic integrated nanocatalyst which combined biocompatible photocatalytic carrier and OPH is designed to remove OPs. H-TiO2 microsphere is prepared using wrinkled SiO2 as template. Then, Au nanoparticles are loaded on the H-TiO2 to obtain Au-H-TiO2 heterojunction microsphere, which achieved effective use of visible light based on the SPR. The characterization results of Au-H-TiO2 prove that the Au-H-TiO2 has large specific surface area (226.19 m2/g) and narrow band gap (2.68 eV). Adsorption methods are used to prepare OPH@Au-H-TiO2 by immobilizing OPH molecules. The obtained OPH@Au-H-TiO2 can degrade methyl parathion to p-NP by OPH. Then the p-NP is degraded to hydroquinone with low toxicity using Au-H-TiO2. After 2.5 h, methyl parathion is completely degraded, and about 82.64% of the generated p-NP is further degraded into hydroquinone. The fabricated OPH@Au-H-TiO2 has excellent catalytic activity and cycle stability, which is ascribed to the photo-enzyme synergic catalytic effect.

Aim: We aimed to evaluate (immunohistochemically) the YAP expression in breast cancer patients undergoing neoadjuvant chemotherapy and to clarify the relationship between the molecular characteristics, treatment response and survival data and the YAP expression, and hence, to clarify the prognostic significance. Methods: One hundred and four patients who were admitted to Erciyes University Faculty of Medicine after the approval of the Ethics Committee and were diagnosed with Breast Cancer between 2015-2020 and underwent NeoAdjuvant Chemotherapy were included in the study. The diagnoses of these patients were determined by any of the methods of Breast USG, Mammography, Breast MRI and, if necessary, PET/CT, and among pathological samples, Estrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal Growth Receptor-2 (HER2) and Ki-67 Expression are routinely stained immunohistochemically. In this study, existing immunohistochemical markers were reviewed and also, the relationship of YAP with these biological markers was evaluated by using immunohistochemistry and its effect on prognosis has been investigated. Results: The average age of the patients was 52.37. While YAP was positive in 78 patients (75%), it was negative in 26 patients (25%). In the evaluation after neoadjuvant therapy, pathological complete response (Miller Payne Grade 5 response) in 28 patients (26.9%), relapse in 6 patients (5.8%), and exitus in 6 patients (5.8%) were detected. In the pathological evaluation, invasive Ductal Carcinoma was the most common one observed in 88 patients (84.6%). As a result of the statistical evaluation, no significant result was obtained between the parameters and YAP negative / positive. Conclusion: As a result of staining with additional YAP in patients who were diagnosed with breast cancer and routinely stained with ER, PR, Cerb B2 and Ki-67 in pathology samples, we could not reach a result that would contribute positively to survival. Longer studies to be conducted prospectively will be meaningful.

Background Essential training for emergency adrenaline auto-injector administration alone provides inadequate safeguard in school environments. Recent UK deaths have reinforced the urgency for embedding whole school (WS) allergy awareness to minimise risk. We document development of a practical, flexible WS Food Allergy Awareness Toolkit for UK secondary schools. Methods We used a multidisciplinary participatory action research methodology, involving successive modification and retesting of a pragmatic toolkit in 3 case study schools. A School Allergy Action Group drives WS risk assessment, helping schools gradually implement best practice policy in line with their particular needs. Additional schools self-piloted the resulting toolkit with only remote monitoring. School surveys, based on EAACI guidelines were developed to identify priorities and assess change. Results Effectiveness of the resulting process toolkit, now available online, was independently demonstrated via pre/post intervention questionnaires from 24/10 pupils with food allergy (FA) and 97/6 pupils without FA, respectively. Pearson correlational analysis showed strong negative relationships between Food Allergy Quality of Life Questionnaire (FAQLQ) at T0 and School Support (SS) at T0 (r=-0.8, p<0.01), and between SS and Self-Efficacy (SE) (r=0.73, p<0.05). Mean FAQLQ scores improved between T0 (3.3) and T1 (2.5). SE improved for those with FA (mean difference =1.0). In those without FA, SE (mean difference =0.9) and Attitudes and Knowledge (mean difference =0.7) also improved. Conclusions Full stakeholder involvement in toolkit development encourages usage and therefore improves WS community awareness; reduces risk of reactions; fosters a more accepting societal attitude; and empowers pupils with/without allergies to self-manage effectively.

Background and purpose: TwHF has been used in traditional Chinese medicines for treating CVD. However, the underlying pharmacological mechanisms of the effects of TwHF against CVD remain to be elucidated. The aim of the present study is to reveal the pharmacological mechanisms of TwHF acting on CVD based on a pharmacology approach. Experimental approach: The active compounds were screened by TCMSP according to ADME. The potential targets of TwHF were predicted by SwissTargetPrediction database. The CVD-related therapeutic targets were obtained by the DrugBank, the OMIM database and the GeneCards database. PPI network was constructed by STRING database. GO and KEGG pathway enrichment analyses were performed by R package. The network of drug‐targets-diseases-pathways was constructed by Cytoscape software. Key results: A total of 51 effective ingredients of TwHF and the 178 common targets of TwHF and CVD-related were collected. AKT1, APP, MAPK, PIK3CA and TP53 was identified the core targets involved in the action of TwHF on CVD. Top ten GO and KEGG pathways were identified with a P value ≤ 0.01. Finally, we constructed the network of TwHF-targets-CVD-GO-KEGG. Conclusion and implications: Our results demonstrated that the main active compound of TwHF exerts cardiovascular protective effects and the core targets and pathways associated with the effects of TwHF on CVD. By the construction of the network of TwHF-targets-CVD-GO-KEGG, network pharmacology uncovered the pharmacological mechanisms of the action of TwHF on CVD and indicated a novel perspective to identify the intricate interactions among TwHF, candidate targets and related pathways.

Stress-induced excessive activation of the adrenergic system or changes in estrogen levels promote the occurrence of arrhythmias. Sodium channel, a responder to β-adrenergic stimulation, is involved in stress-induced cardiac electrophysiological abnormalities. However, it has not been established whether estrogen regulates sodium channels during acute stress. Our study aimed to explore whether voltage-gated sodium channels play roles in the rapid regulation of various concentrations of estrogen in stressed human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), and reveal the possible mechanism of estrogen signaling pathway modulating stress. An isoproterenol-induced stress model of hiPSC-CMs was pre-incubated with β-Estradiol at different concentrations (0.01 nmol/L, 1 nmol/L, and 100 nmol/L). Action potential (AP) and sodium currents were detected by patch clamp. The G protein-coupled estrogen receptor (GPER)-specific effect was determined with agonists G1, antagonists G15 and small interfering RNA. β-Estradiol at concentrations of 0.01 nmol/L, 1 nmol/L, and 100 nmol/L increased the peak sodium current and prolonged AP duration (APD) at 1 nmol/L. Stress increased peak sodium current, late sodium current, and shortened APD. The effects of stress on sodium currents and APD were eliminated by β-Estradiol. Activation of GPER by G1 exhibited similar effects as β-Estradiol, while inhibition of GPER with G15 and small interfering RNA ameliorated estrogenic actions. Estrogen, antagonized the stress-related abnormal electrical activity, and through GPER alleviated sodium channel dysfunctions in stress state in hiPSC-CMs. These results provide a novel mechanism through which estrogenic rapid signaling against stress by regulating ion channels.

Many drugs are responsible, through different mechanisms, for peripheral edema. Severity is highly variable ranging from slight edema of the lower limbs to anasarca pictures as in the capillary leak syndrome. Although most often non-inflammatory and bilateral, some drugs are associated with peripheral edema that is readily erythematous (e.g., dopaminergic agonists, pemetrexed) or unilateral (e.g., sirolimus). Thus, drug-induced peripheral edema is underrecognized and misdiagnosed, frequently leading to a prescribing cascade. Four main mechanisms are involved, namely precapillary arteriolar vasodilation (vasodilatory edema), sodium/water retention (renal edema), lymphatic insufficiency (lymphedema) and increased capillary permeability (permeability edema). The underlying mechanism has significant impact on treatment efficacy. This review provides a comprehensive analysis of the main causative drugs by illustrating each pathophysiological mechanism and their management through an example of drug.

Terrestrial biosphere models (TBMs) are extremely sensitive to the parameterization of the Farquhar, von Caemmerer & Berry model of photosynthesis, particularly the apparent maximum carboxylation capacity (Vcmax) of Rubisco. New instrumentation and approaches have enabled the rapid measurement of apparent Vcmax that paves the way for the investigation of diurnal variation in Vcmax and improved understanding of the potential impact on representation of photosynthesis in TBMs. Here we show that reductions in Vcmax over the course of a photoperiod can be as great as 50% and, when incorporated into a model of daily CO2 assimilation, show that net carbon gain can change between -19 and 215% when compared to the current TBM assumption of a constant Vcmax. Given the obvious impact on TBM representation of photosynthesis, we recommend a renewed focus on the measurement of diurnal responses in photosynthetic capacity across biomes to advance understanding and enable model representation of this important phenomenon.