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Linking functional traits to multiscale statistics of leaf venation networks

Blonder B, Both S, Jodra M, Xu H, Fricker M, Matos IS, et al.

New Phytol, 2020 12;228(6):1796-1810.
PMID: 32712991 DOI: 10.1111/nph.16830

Leaf venation networks evolved along several functional axes, including resource transport, damage resistance, mechanical strength, and construction cost. Because functions may depend on architectural features at different scales, network architecture may vary across spatial scales to satisfy functional tradeoffs. We develop a framework for quantifying network architecture with multiscale statistics describing elongation ratios, circularity ratios, vein density, and minimum spanning tree ratios. We quantify vein networks for leaves of 260 southeast Asian tree species in samples of up to 2 cm2 , pairing multiscale statistics with traits representing axes of resource transport, damage resistance, mechanical strength, and cost. We show that these multiscale statistics clearly differentiate species' architecture and delineate a phenotype space that shifts at larger scales; functional linkages vary with scale and are weak, with vein density, minimum spanning tree ratio, and circularity ratio linked to mechanical strength (measured by force to punch) and elongation ratio and circularity ratio linked to damage resistance (measured by tannins); and phylogenetic conservatism of network architecture is low but scale-dependent. This work provides tools to quantify the function and evolution of venation networks. Future studies including primary and secondary veins may uncover additional insights.
The role of competitive counterion adsorption on the electrolyte induced surface ordering in methyl ester sulfonate surfactants at the air-water interface

Xu H, Li P, Ma K, Welbourn RJL, Penfold J, Thomas RK, et al.

J Colloid Interface Sci, 2019 Jan 01;533:154-160.
PMID: 30153592 DOI: 10.1016/j.jcis.2018.08.061

The strong binding of Al3+ trivalent counterions to the anionic surfactants sodium polyethylene glycol monoalkyl ether sulfate and α-methyl ester sulfonate results in surface multilayer formation at the air-water interface. In contrast the divalent and monovalent counterions Ca2+ and Na+ result only in monolayer adsorption. Competitive counterion adsorption has been extensively studied in the context of surfactant precipitation and re-dissolution, but remains an important feature in understanding this surface ordering and how it can be manipulated. The α-methyl ester sulfonate surfactants are a promising class of anionic surfactants which have much potential for improved performance in many applications, greater tolerance to extreme solvent conditions such as water hardness, biocompatibility and sustainable production. Hence in this study we have used neutron reflectivity to extend previous studies on the surface ordering of the α-methyl ester sulfonate surfactant, sodium tetradecanoic 2-sulfo 1-methyl ester, in the presence of electrolyte to investigate the role of binary mixtures of electrolytes, AlCl3/CaCl2, and AlCl3/MgCl2. In the mixed electrolytes the evolution of the surface structure, from monolayer to multilayer with increasing AlCl3 concentration, is observed. It is broadly similar to that reported for the addition of only AlCl3. However with increasing CaCl2 concentration the structural evolution is shifted progressively to higher AlCl3 concentrations. Similar observations occur for the AlCl3/MgCl2 mixtures. However the presence of the MgCl2 results in an additional phenomenon; the partial co-adsorption of a more compact lamellar structure which exists until the highest AlCl3 concentrations. The results demonstrate the importance of the competitive adsorption of different counterions in driving and controlling the formation of surface multilayer structures with anionic surfactants. Furthermore it offers a facile route to the manipulation of these surface structures.
Impact of molecular structure, headgroup and alkyl chain geometry, on the adsorption of the anionic ester sulfonate surfactants at the air-solution interface, in the presence and absence of electrolyte

Wang Z, Li P, Ma K, Chen Y, Campana M, Penfold J, et al.

J Colloid Interface Sci, 2019 May 15;544:293-302.
PMID: 30861434 DOI: 10.1016/j.jcis.2019.03.011

The transition from monolayer to multilayer adsorption at the air-water interface in the presence of multivalent counterions has been demonstrated for a limited range of anionic surfactants which exhibit increased tolerance to precipitation in the presence of multivalent counterions. Understanding the role of molecular structure in determining the transition to surface ordering is an important aspect of the phenomenon. The focus of the paper is on the alkyl ester sulfonate, AES, surfactants; a promising group of anionic surfactants, with the potential for improved performance and biocompatibility. Neutron reflectivity measurements were made in aqueous solution and in the presence of NaCl, CaCl2, MgCl2 and AlCl3, for a range of alkyl ester sulfonate surfactants, in which the headgroup and alkyl chain geometries were manipulated. In the regions of monolayer adsorption changing the AES headgroup and alkyl chain geometries results in an increased saturation adsorption and in a more gradual decrease in the adsorption at low concentrations, consistent with a greater adsorption efficiency. Changing the AES headgroup and alkyl chain geometries also results in changes in the transition from monolayer adsorption to more ordered surface structures with the addition of AlCl3 and mixed multivalent electrolytes. A more limited surface layering is observed for the ethyl ester sulfonate, EES, with a C14 alkyl chain. Replacing the C14 alkyl chain with a C18 isostearic chain results in only monolayer adsorption. The results demonstrate the role and importance of the surfactant molecular structure in determining the nature of the surface adsorption in the presence of different electrolytes, and in the tendency to form extended surface multilayer structures.
Fish-borne trematode metacercariae detected in fish commonly used for raw consumption in Ninh Binh Province, Vietnam

Khoa DV, Hoa DT, Anh DN, Van NT, Dung DT, Huong LTT, et al.

Trop Biomed, 2020 Jun 01;37(2):443-451.
PMID: 33612813

Raw or undercooked fish dishes are the major sources of human infection of fishborne trematodes (FBT) and the situation of metacercarial infection in fish greatly affect the prevalence in humans, especially those fish that are commonly used for raw consumption. To investigate the situation of infection with metacercaria of FBT in fish often used to prepare raw fish dishes by local people to assess the risk of infection to humans in Ninh Binh province, Vietnam. 345 fish belonging to five species of freshwater and one species of brackish water fish were collected from fishermen or small-scale fish dealers in Kim Son and Yen Khanh districts, Ninh Binh province between May 2017 and May 2018. Metacercaria of FBT was discovered by pepsin and hydrochloric acid digestion techniques and identified by the morphological and molecular analysis. Among examined fish, 44.06% infected with FBT metacercaria and the highest prevalence was in Cyprinus carpio (86.54%), Ctenopharyngodon idellus (78.43%) and Hypophthalmichthys molitrix (66.67%) while Konosirus punctatus - the brackish water fish - were free from infection. Three species of FBT were found; namely Haplorchis pumilio (accounting for 99.84% of collected metacercariae), Haplorchis taichui and Clonorchis sinensis. The average density was 1.06 metacercariae per gram of freshwater fish and the highest number was of C. idellus (6.38 cysts/gram) followed by Cirrhinus molitorella and C. carpio. Results of the study show the high prevalence of infection of FBT metacercariae among freshwater fish often used to prepare raw fish dishes in Ninh Binh province. These findings suggest the need for greater awareness of the risk from raw fish dishes among public health authorities and people.
SNHG16 promotes cell proliferation and inhibits cell apoptosis via regulation of the miR-1303-p/STARD9 axis in clear cell renal cell carcinoma

Cheng T, Shuang W, Ye D, Zhang W, Yang Z, Fang W, et al.

Cell Signal, 2021 08;84:110013.
PMID: 33901578 DOI: 10.1016/j.cellsig.2021.110013

Clear cell renal cell carcinoma (ccRCC) is a common subtype of renal cell carcinoma (RCC) and causes many deaths. Numerous medical studies have suggested that long noncoding RNAs (lncRNAs) exert their biological functions on ccRCC. Herein, functions of lncRNA SNHG16 in ccRCC cells and the mechanism mediated by SNHG16 were investigated. The expression levels of SNHG16 and its downstream genes in ccRCC cells and RCC tissues were examined utilizing reverse transcription quantitative polymerase chain reaction analyses. Cell counting kit-8 and 5-Ethynyl-2'-deoxyuridine assays were performed to evaluate the proliferation of ccRCC cells, and flow cytometry analyses were employed to determine the apoptosis of ccRCC cells. Western blot analysis was applied to examine protein levels associated with cell proliferation and apoptosis. The combination between SNHG16 and miRNA as well as miRNA and its target gene were explored by luciferase reporter, RNA pull down, and RNA immunoprecipitation assays. The significant upregulation of SNHG16 was observed in RCC tissues and ccRCC cells. SNHG16 downregulation inhibited the proliferation and promoted the apoptosis of ccRCC cells. In addition, SNHG16 served as a competing endogenous RNA for miR-1301-3p, and STARD9 was a target gene of miR-1301-3p in ccRCC cells. SNHG16 upregulated STARD9 expression by binding with miR-1301-3p in ccRCC cells. Rescue assays validated that SNHG16 promoted ccRCC cell promotion and induced ccRCC cell apoptosis by upregulating STARD9 expression. In conclusions, SNHG16 promotes ccRCC cell proliferation and suppresses ccRCC cell apoptosis via interaction with miR-1301-3p to upregulate STARD9 expression in ccRCC cells.
Fulltext Towards a Framework for Better Understanding of Quiescent Cancer Cells

Nik Nabil WN, Xi Z, Song Z, Jin L, Zhang XD, Zhou H, et al.

Cells, 2021 03 05;10(3).
PMID: 33807533 DOI: 10.3390/cells10030562

Quiescent cancer cells (QCCs) are cancer cells that are reversibly suspended in G0 phase with the ability to re-enter the cell cycle and initiate tumor growth, and, ultimately, cancer recurrence and metastasis. QCCs are also therapeutically challenging due to their resistance to most conventional cancer treatments that selectively act on proliferating cells. Considering the significant impact of QCCs on cancer progression and treatment, better understanding of appropriate experimental models, and the evaluation of QCCs are key questions in the field that have direct influence on potential pharmacological interventions. Here, this review focuses on existing and emerging preclinical models and detection methods for QCCs and discusses their respective features and scope for application. By providing a framework for selecting appropriate experimental models and investigative methods, the identification of the key players that regulate the survival and activation of QCCs and the development of more effective QCC-targeting therapeutic agents may mitigate the consequences of QCCs.
Adsorption of Methyl Ester Sulfonate at the Air-Water Interface: Can Limitations in the Application of the Gibbs Equation be Overcome by Computer Purification?

Xu H, Li P, Ma K, Welbourn RJL, Penfold J, Roberts DW, et al.

Langmuir, 2017 09 26;33(38):9944-9953.
PMID: 28871785 DOI: 10.1021/acs.langmuir.7b02725

We describe a new laboratory synthesis of the α-methyl ester sulfonates based on direct sulfonation of the methyl ester by SO3 introduced from the vapor phase. This was used to synthesize a chain deuterated sample of αC14MES, which was then used to measure the surface excess of αC14MES directly at the air/water interface over a wide range of concentration using neutron reflection. The adsorption isotherm could be fitted to an empirical equation close to a Langmuir isotherm and gave a limiting surface excess of (3.4 ± 0.1) × 10-6 mol m-2 in the absence of added electrolyte. The neutron-measured surface excesses were combined with the integrated Gibbs equation to fit the variation in surface tension with concentration (σ-ln C curve). The fit was exact provided that we used a prefactor consistent with the counterion at the surface being an impurity divalent ion, as has previously been found for sodium diethylhexylsulfosuccinate (aerosol OT or AOT) and various perfluorooctanoates. The critical micelle concentration (CMC) was determined from this fit to be 2.4 ± 0.3 mM in the absence of electrolyte. In the presence of 100 mM NaCl, this contamination was suppressed and the σ-ln C curve could be fitted using the integrated Gibbs equation with the expected prefactor of 1. The new data were used to reinterpret measurements by Danov et al. on an unpurified sample of αC14MES for which computer refinement was used to try to eliminate the effects of the impurities.
Fulltext Saikosaponin A enhances Docetaxel efficacy by selectively inducing death of dormant prostate cancer cells through excessive autophagy

Feng J, Xi Z, Jiang X, Li Y, Nik Nabil WN, Liu M, et al.

Cancer Lett, 2023 Feb 01;554:216011.
PMID: 36442771 DOI: 10.1016/j.canlet.2022.216011

Quiescent cancer cells (QCCs), also known as dormant cancer cells, resist and survive chemo- and radiotherapy, resulting in treatment failure and later cancer recurrence when QCCs resume cell cycle progression. However, drugs selectively targeting QCCs are lacking. Saikosaponin A (SSA) derived from Bupleurum DC., is highly potent in eradicating multidrug-resistant prostate QCCs compared with proliferative prostate cancer cells. By further exacerbating the already increased autophagy through inactivation of Akt-mTOR signaling, SSA triggered cell death in QCCs. Contrarily, inhibition of autophagy or activation of Akt signaling pathway prevented SSA-induced cell death. The multicycle of Docetaxel treatments increased the proportion of QCCs, whereas administering SSA at intervals of Docetaxel treatments aggravated cell death in vitro and led to tumor growth arrest and cell death in vivo. In conclusion, SSA is posed as a novel QCCs-eradicating agent by aggravating autophagy in QCCs. In combination with the current therapy, SSA has potential to improve treatment effectiveness and to prevent cancer recurrence.
Enhanced solubility of methyl ester sulfonates below their Krafft points in mixed micellar solutions

Yavrukova VI, Danov KD, Slavova TG, Stanimirova RD, Wei Ung Y, Tong Kim Suan A, et al.

J Colloid Interface Sci, 2024 Jan 22;660:896-906.
PMID: 38280282 DOI: 10.1016/j.jcis.2024.01.127

HYPOTHESIS: Methyl ester sulfonates (MES) show limited water solubility at lower temperatures (Krafft point). One way to increase their solubility below their Krafft points is to incorporate them in anionic surfactant micelles. The electrostatic interactions between the ionic surfactant molecules and charged micelles play an important role for the degree of MES solubility.
EXPERIMENTS: The solubility and electrolytic conductivity for binary and ternary surfactant mixtures of MES with anionic sodium alpha olefin sulfonate (AOS) and sodium lauryl ether sulfate with two ethylene oxide groups (SLES-2EO) at 5 °C during long-term storage were measured. Phase diagrams were established; a general phase separation theoretical model for their explanation was developed and checked experimentally.
FINDINGS: The binary and ternary phase diagrams for studied surfactant mixtures include phase domains: mixed micelles; micelles + crystallites; crystallites, and molecular solution. The proposed general phase separation model for ionic surfactant mixtures is convenient for construction of such complex phase diagrams and provides information on the concentrations of all components of the complex solution and on the micellar electrostatic potential. The obtained maximal MES mole fraction of transparent micellar solutions could be of interest to increase the range of applicability of MES-surfactants.
Fulltext Best practices for managing malodorous and infected wounds in advanced cervical cancer

Hamid HA, Lin X, Qin YK, Akim AM, Zhang L, Wang J, et al.

Int Wound J, 2024 Feb;21(2):e14574.
PMID: 38379231 DOI: 10.1111/iwj.14574

This cross-sectional study was conducted to examine the most effective strategies for managing malodorous and infected wounds in patients who have been diagnosed with advanced cervical cancer. The research was conducted in Liupanshui, China. The study specifically examined demographic profiles, wound characteristics and effectiveness of wound management approaches. The study incorporated the heterogeneous sample of 289 participants who fulfilled the inclusion criteria. Data collection was conducted via structured questionnaires and medical record evaluations. Descriptive statistics and statistical analyses, such as regression analysis, were utilized to evaluate demographic attributes, wound profiles and effects of different approaches to wound management. The findings unveiled the heterogeneous demographic composition of patients, encompassing differences in socioeconomic standing, educational attainment and age. A wide range of wound characteristics were observed, as 65.7% of lesions during the acute phase with diameter between 2 and 5 centimetres, while 41.5% of lesions had this range. The most prevalent types of infections were those caused by fungi (48.4%), followed by bacterial infections lacking resistance (38.1%). A moderate degree of odour intensity was prevalent, affecting 45.0% of the cases. With maximal odour reduction of 80%, a mean healing time of 25 days and patient satisfaction rating of 4.5 out of 5, Negative Pressure Wound Therapy demonstrated itself to be the most efficacious treatment method. Additional approaches, such as photodynamic therapy and topical antibiotic therapy, demonstrated significant effectiveness, as evidenced by odour reductions of 70% and 75%, respectively, and patient satisfaction ratings of 4.3 and 4.2. Thus, the study determined challenges associated with management of malodorous and infected lesions among patients with advanced cervical cancer. The results underscored the significance of individualized care approaches, drew attention to efficacious wound management techniques and identified critical determinants that impacted patient recuperation. The findings of this study hold potential for advancing palliative care for individuals diagnosed with advanced cervical cancer.
The structure of alkyl ester sulfonate surfactant micelles: The impact of different valence electrolytes and surfactant structure on micelle growth

Wang Z, Li P, Ma K, Chen Y, Penfold J, Thomas RK, et al.

J Colloid Interface Sci, 2019 Sep 05;557:124-134.
PMID: 31518834 DOI: 10.1016/j.jcis.2019.09.016

The ester sulfonate anionic surfactants are a potentially valuable class of sustainable surfactants. The micellar growth, associated rheological changes, and the onset of precipitation are important consequences of the addition of electrolyte and especially multi-valent electrolytes in anionic surfactants. Small angle neutron scattering, SANS, has been used to investigate the self-assembly and the impact of different valence electrolytes on the self-assembly of a range of ester sulfonate surfactants with subtly different molecular structures. The results show that in the absence of electrolyte small globular micelles form, and in the presence of NaCl, and AlCl3 relatively modest micellar growth occurs before the onset of precipitation. The micellar growth is more pronounced for the longer unbranched and branched alkyl chain lengths. Whereas changing the headgroup geometry from methyl ester to ethyl ester has in general a less profound impact. The study highlights the importance of relative counterion binding strengths and shows how the surfactant structure affects the counterion binding and hence the micelle structure. The results have important consequences for the response of such surfactants to different operational environments.
α-Sulfo alkyl ester surfactants: Impact of changing the alkyl chain length on the adsorption, mixing properties and response to electrolytes of the tetradecanoate

Wang Z, Li P, Ma K, Chen Y, Yan Z, Penfold J, et al.

J Colloid Interface Sci, 2021 Mar 15;586:876-890.
PMID: 33309145 DOI: 10.1016/j.jcis.2020.10.122

HYPOTHESIS: The α-sulfo alkyl ester, AES, surfactants are a class of anionic surfactants which have potential for improved sustainable performance in a range of applications, and an important feature is their enhanced tolerance to precipitation in the presence of multivalent counterions. It is proposed that their adsorption properties can be adjusted substantially by changing the length of the shorter alkyl chain, that of the alkanol group in the ester.
EXPERIMENTS: Surface tension and neutron reflectivity have been used to investigate the variation in the adsorption properties with the shorter alkyl chain length (methyl, ethyl and propyl), the impact of NaCl on the adsorption, the tendency to form surface multilayer structures in the presence of AlCl3, and the effects of mixing the methyl ester sulfonate with the ethyl and propyl ester sulfonates on the adsorption.
FINDINGS: The variations in the critical micelle concentration, CMC, the adsorption isotherms, the saturation adsorption values, and the impact of NaCl illustrate the subtle influence of varying the shorter alkyl chain length of the surfactant. The non-ideal mixing of pairs of AES surfactants with different alkanol group lengths of the ester show that the extent of the non-ideality changes as the difference in the alkanol length increases. The surface multilayer formation observed in the presence of AlCl3 varies in a complex manner with the length of the short chain and for mixtures of surfactants with different chains lengths.
Adsorption and self-assembly in methyl ester sulfonate surfactants, their eutectic mixtures and the role of electrolyte

Xu H, Li P, Ma K, Welbourn RJL, Doutch J, Penfold J, et al.

J Colloid Interface Sci, 2018 Apr 15;516:456-465.
PMID: 29408135 DOI: 10.1016/j.jcis.2018.01.086

The α-methyl ester sulfonate, MES, anionic surfactants are a potentially important class of sustainable surfactants for a wide range of applications. The eutectic-like Kraft point minimum in the C16 and C18-MES mixtures is an important feature of that potential. Understanding their individual adsorption properties and the surface mixing of the eutectic mixtures are key to their wider exploitation. Neutron reflectivity has been used to investigate the adsorption at the air-water interface of the C16 and C18-MES surfactants and the eutectic mixture of C16 and C18-MES, in aqueous solution and in electrolyte. The micelle mixing of the eutectic mixture is investigated using small angle neutron scattering. The adsorption isotherms for C14 to C18-MES are found to scale with their critical micelle concentration value. The surface and micelle compositions of the C16 and C18-MES eutectic mixture differ from the eutectic composition; with compositions in the limit of high concentrations richer in C16-MES. The mixing properties are described by the pseudo phase approximation with a repulsive interaction between the two surfactants. The impact of the multivalent ions Al3+ on the adsorption at the air-water interface results in a transition from monolayer to multilayer adsorption.
Pulsatilla Decoction and its bioactive component β-peltatin induce G2/M cell cycle arrest and apoptosis in pancreatic cancer

Wu R, Xi Z, Liu M, Ren H, Dai R, Jiang X, et al.

Chin Med, 2023 May 28;18(1):61.
PMID: 37246229 DOI: 10.1186/s13020-023-00774-0

BACKGROUND: Pancreatic cancer (PAC), a malignancy that is fatal and commonly diagnosed at a late stage. Despite considerable advancements in cancer treatment, the survival rate of PAC remains largely consistent for the past 60 years. The traditional Chinese medicine formula Pulsatilla Decoction (PD) has been clinically used to treat inflammatory diseases for millennia and recently as a supplementary anti-cancer treatment in China. However, the bioactive ingredients and mechanisms underlying its anti-cancer effect remains unclear.
METHODS: The composition and quality control of PD were verified through analysis by high performance liquid chromatography. Cell viability was determined using Cell Counting Kit-8 assay. The cell cycle distribution was analyzed through PI staining and flow cytometry analysis, while apoptotic cells were measured by double staining with Annexin V-FITC and PI. We used immunoblotting to examine protein expressions. The in vivo effects of β-peltatin and podophyllotoxin were evaluated on a subcutaneously-xenografted BxPC-3 cell nude mice model.
RESULTS: The current study demonstrated that PD markedly inhibited PAC cell proliferation and triggered their apoptosis. Four herbal PD formula was then disassembled into 15 combinations of herbal ingredients and a cytotoxicity assay showed that the Pulsatillae chinensis exerted the predominant anti-PAC effect. Further investigation indicated that β-peltatin was potently cytotoxic with IC50 of ~ 2 nM. β-peltatin initially arrested PAC cells at G2/M phase, followed by apoptosis induction. Animal study confirmed that β-peltatin significantly suppressed the growth of subcutaneously-implanted BxPC-3 cell xenografts. Importantly, compared to podophyllotoxin that is the parental isomer of β-peltatin but clinically obsoleted due to its severe toxicity, β-peltatin exhibited stronger anti-PAC effect and lower toxicity in mice.
CONCLUSIONS: Our results demonstrate that Pulsatillae chinensis and particularly its bioactive ingredient β-peltatin suppress PAC by triggering cell cycle arrest at G2/M phase and apoptosis.
Fulltext Enhanced exclusive enteral nutrition delivery during the first 7 days is associated with decreased 28-day mortality in critically ill patients with normal lactate level: a post hoc analysis of a multicenter randomized trial

Chen Y, Liu Z, Wang Q, Gao F, Xu H, Ke L, et al.

Crit Care, 2024 Jan 20;28(1):26.
PMID: 38245768 DOI: 10.1186/s13054-024-04813-6

BACKGROUND AND AIMS: Exclusive enteral nutrition (EN) is often observed during the first week of ICU admission because of the extra costs and safety considerations for early parenteral nutrition. This study aimed to assess the association between nutrition intake and 28-day mortality in critically ill patients receiving exclusive EN.
METHODS: This is a post hoc analysis of a cluster-randomized clinical trial that assesses the effect of implementing a feeding protocol on mortality in critically ill patients. Patients who stayed in the ICUs for at least 7 days and received exclusive EN were included in this analysis. Multivariable Cox hazard regression models and restricted cubic spline models were used to assess the relationship between the different doses of EN delivery and 28-day mortality. Subgroups with varying lactate levels at enrollment were additionally analyzed to address the potential confounding effect brought in by the presence of shock-related hypoperfusion.
RESULTS: Overall, 1322 patients were included in the analysis. The median (interquartile range) daily energy and protein delivery during the first week of enrollment were 14.6 (10.3-19.6) kcal/kg and 0.6 (0.4-0.8) g/kg, respectively. An increase of 5 kcal/kg energy delivery was associated with a significant reduction (approximately 14%) in 28-day mortality (adjusted hazard ratio [HR] = 0.865, 95% confidence interval [CI]: 0.768-0.974, P = 0.016). For protein intake, a 0.2 g/kg increase was associated with a similar mortality reduction with an adjusted HR of 0.868 (95% CI 0.770-0.979). However, the benefits associated with enhanced nutrition delivery could be observed in patients with lactate concentration ≤ 2 mmol/L (adjusted HR = 0.804 (95% CI 0.674-0.960) for energy delivery and adjusted HR = 0.804 (95% CI 0.672-0.962) for protein delivery, respectively), but not in those > 2 mmol/L.
CONCLUSIONS: During the first week of critical illness, enhanced nutrition delivery is associated with reduced mortality in critically ill patients receiving exclusive EN, only for those with lactate concentration ≤ 2 mmol/L.
TRIAL REGISTRATION: ISRCTN12233792, registered on November 24, 2017.
High Frequency of Allergic Bronchopulmonary Aspergillosis in Bronchiectasis-COPD Overlap

Tiew PY, Lim AYH, Keir HR, Dicker AJ, Mac Aogáin M, Pang SL, et al.

Chest, 2022 01;161(1):40-53.
PMID: 34364870 DOI: 10.1016/j.chest.2021.07.2165

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is associated with frequent exacerbations and poor outcomes in chronic respiratory disease, but remains underdiagnosed. The role of fungal sensitization in bronchiectasis-COPD overlap (BCO) is unknown.
RESEARCH QUESTION: What is the occurrence and clinical relevance of Aspergillus sensitization and ABPA in BCO when compared with individuals with COPD or bronchiectasis without overlap?
STUDY DESIGN: Prospective, observational, cross-sectional study.
METHODS: We prospectively recruited 280 patients during periods of clinical stability with bronchiectasis (n = 183), COPD (n = 50), and BCO (n = 47) from six hospitals across three countries (Singapore, Malaysia, and Scotland). We assessed sensitization responses (as specific IgE) to a panel of recombinant Aspergillus fumigatus allergens and the occurrence of ABPA in relationship to clinical outcomes.
RESULTS: Individuals with BCO show an increased frequency and clinical severity of ABPA compared with those with COPD and bronchiectasis without overlap. BCO-associated ABPA is associated with more severe disease, higher exacerbation rates, and lower lung function when compared with ABPA occurring in the absence of overlap. BCO with a severe bronchiectasis severity index (BSI; > 9) is associated significantly with the occurrence of ABPA that is unrelated to underlying COPD severity.
CONCLUSIONS: BCO demonstrates a high frequency of ABPA that is associated with a severe BSI (> 9) and poor clinical outcomes. Clinicians should maintain a high index of suspicion for the potential development of ABPA in patients with BCO with high BSI.
The future of scientific societies

da Silva CFA, Virgüez E, Eker S, Zdenek CN, Bergh C, Gerarduzzi C, et al.

Science, 2023 Apr 07;380(6640):30-32.
PMID: 37023192 DOI: 10.1126/science.adh8182
Fulltext A high-risk airway mycobiome is associated with frequent exacerbation and mortality in COPD

Tiew PY, Dicker AJ, Keir HR, Poh ME, Pang SL, Mac Aogáin M, et al.

Eur Respir J, 2021 Mar;57(3).
PMID: 32972986 DOI: 10.1183/13993003.02050-2020

INTRODUCTION: The chronic obstructive pulmonary disease (COPD) bacteriome associates with disease severity, exacerbations and mortality. While COPD patients are susceptible to fungal sensitisation, the role of the fungal mycobiome remains uncertain.
METHODS: We report the largest multicentre evaluation of the COPD airway mycobiome to date, including participants from Asia (Singapore and Malaysia) and the UK (Scotland) when stable (n=337) and during exacerbations (n=66) as well as nondiseased (healthy) controls (n=47). Longitudinal mycobiome analysis was performed during and following COPD exacerbations (n=34), and examined in terms of exacerbation frequency, 2-year mortality and occurrence of serum specific IgE (sIgE) against selected fungi.
RESULTS: A distinct mycobiome profile is observed in COPD compared with controls as evidenced by increased α-diversity (Shannon index; p<0.001). Significant airway mycobiome differences, including greater interfungal interaction (by co-occurrence), characterise very frequent COPD exacerbators (three or more exacerbations per year) (permutational multivariate ANOVA; adjusted p<0.001). Longitudinal analyses during exacerbations and following treatment with antibiotics and corticosteroids did not reveal any significant change in airway mycobiome profile. Unsupervised clustering resulted in two clinically distinct COPD groups: one with increased symptoms (COPD Assessment Test score) and Saccharomyces dominance, and another with very frequent exacerbations and higher mortality characterised by Aspergillus, Curvularia and Penicillium with a concomitant increase in serum sIgE levels against the same fungi. During acute exacerbations of COPD, lower fungal diversity associates with higher 2-year mortality.
CONCLUSION: The airway mycobiome in COPD is characterised by specific fungal genera associated with exacerbations and increased mortality.
Fulltext IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome

Trautmann A, Vivarelli M, Samuel S, Gipson D, Sinha A, Schaefer F, et al.

Pediatr Nephrol, 2020 Aug;35(8):1529-1561.
PMID: 32382828 DOI: 10.1007/s00467-020-04519-1

Idiopathic nephrotic syndrome newly affects 1-3 per 100,000 children per year. Approximately 85% of cases show complete remission of proteinuria following glucocorticoid treatment. Patients who do not achieve complete remission within 4-6 weeks of glucocorticoid treatment have steroid-resistant nephrotic syndrome (SRNS). In 10-30% of steroid-resistant patients, mutations in podocyte-associated genes can be detected, whereas an undefined circulating factor of immune origin is assumed in the remaining ones. Diagnosis and management of SRNS is a great challenge due to its heterogeneous etiology, frequent lack of remission by further immunosuppressive treatment, and severe complications including the development of end-stage kidney disease and recurrence after renal transplantation. A team of experts including pediatric nephrologists and renal geneticists from the International Pediatric Nephrology Association (IPNA), a renal pathologist, and an adult nephrologist have now developed comprehensive clinical practice recommendations on the diagnosis and management of SRNS in children. The team performed a systematic literature review on 9 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions, formulated recommendations and formally graded them at a consensus meeting, with input from patient representatives and a dietician acting as external advisors and a voting panel of pediatric nephrologists. Research recommendations are also given.
Fulltext Sensitisation to recombinant Aspergillus fumigatus allergens and clinical outcomes in COPD

Tiew PY, Narayana JK, Quek MSL, Ang YY, Ko FWS, Poh ME, et al.

Eur Respir J, 2023 Jan;61(1).
PMID: 35926878 DOI: 10.1183/13993003.00507-2022

BACKGROUND: Variable clinical outcomes are reported with fungal sensitisation in chronic obstructive pulmonary disease (COPD), and it remains unclear which fungi and what allergens associate with the poorest outcomes. The use of recombinant as opposed to crude allergens for such assessment is unknown.
METHODS: A prospective multicentre assessment of stable COPD (n=614) was undertaken in five hospitals across three countries: Singapore, Malaysia and Hong Kong. Clinical and serological assessment was performed against a panel of 35 fungal allergens including crude and recombinant Aspergillus and non-Aspergillus allergens. Unsupervised clustering and topological data analysis (TDA) approaches were employed using the measured sensitisation responses to elucidate if sensitisation subgroups exist and their related clinical outcomes.
RESULTS: Aspergillus fumigatus sensitisation was associated with increased exacerbations in COPD. Unsupervised cluster analyses revealed two "fungal sensitisation" groups. The first was characterised by Aspergillus sensitisation and increased exacerbations, poorer lung function and worse prognosis. Polysensitisation in this group conferred even poorer outcome. The second group, characterised by Cladosporium sensitisation, was more symptomatic. Significant numbers of individuals demonstrated sensitisation responses to only recombinant (as opposed to crude) A. fumigatus allergens f 1, 3, 5 and 6, and exhibited increased exacerbations, poorer lung function and an overall worse prognosis. TDA validated these findings and additionally identified a subgroup within Aspergillus-sensitised COPD of patients with frequent exacerbations.
CONCLUSION: Aspergillus sensitisation is a treatable trait in COPD. Measuring sensitisation responses to recombinant Aspergillus allergens identifies an important patient subgroup with poor COPD outcomes that remains overlooked by assessment of only crude Aspergillus allergens.

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