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Fulltext Malaysian and Chinese King Cobra Venom Cytotoxicity in Melanoma and Neonatal Foreskin Fibroblasts Is Mediated by Age and Geography

Op den Brouw B, Fernandez-Rojo MA, Charlton T, Fry BG, Ikonomopoulou MP

Toxins (Basel), 2023 Sep 04;15(9).
PMID: 37755975 DOI: 10.3390/toxins15090549

Snake venoms constitute a complex, rapidly evolving trait, whose composition varies between and within populations depending on geographical location, age and preys (diets). These factors have determined the adaptive evolution for predatory success and link venom heterogeneity with prey specificity. Moreover, understanding the evolutionary drivers of animal venoms has streamlined the biodiscovery of venom-derived compounds as drug candidates in biomedicine and biotechnology. The king cobra (Ophiophagus hannah; Cantor, 1836) is distributed in diverse habitats, forming independent populations, which confer differing scale markings, including between hatchlings and adults. Furthermore, king cobra venoms possess unique cytotoxic properties that are used as a defensive trait, but their toxins may also have utility as promising anticancer-agent candidates. However, the impact of geographical distribution and age on these potential venom applications has been typically neglected. In this study, we hypothesised that ontogenetic venom variation accompanies the morphological distinction between hatchlings and adults. We used non-transformed neonatal foreskin (NFF) fibroblasts to examine and compare the variability of venom cytotoxicity between adult captive breeding pairs from Malaysian and Chinese lineages, along with that of their progeny upon hatching. In parallel, we assessed the anticancer potential of these venoms in human-melanoma-patient-derived cells (MM96L). We found that in a geographical distribution and gender-independent manner, venoms from hatchlings were significantly less cytotoxic than those from adults (NFF; ~Log EC50: 0.5-0.6 vs. 0.2-0.35 mg/mL). This is consistent with neonates occupying a semifossorial habitat, while adults inhabit more above-ground habitats and are therefore more conspicuous to potential predators. We also observed that Malaysian venoms exhibited a slightly higher cytotoxicity than those from the Chinese cobra cohorts (NFF; Log EC50: 0.1-0.3 vs. 0.3-0.4 mg/mL), which is consistent with Malaysian king cobras being more strongly aposematically marked. These variations are therefore suggestive of differential anti-predator strategies associated with the occupation of distinct niches. However, all cobra venoms were similarly cytotoxic in both melanoma cells and fibroblasts, limiting their potential medical applications in their native forms.
Fulltext Antisolvent Additive Engineering for Boosting Performance and Stability of Graded Heterojunction Perovskite Solar Cells Using Amide-Functionalized Graphene Quantum Dots

Khorshidi E, Rezaei B, Kavousighahfarokhi A, Hanisch J, Reus MA, Müller-Buschbaum P, et al.

ACS Appl Mater Interfaces, 2022 Dec 14;14(49):54623-54634.
PMID: 36446022 DOI: 10.1021/acsami.2c12944

Additive and antisolvent engineering strategies are outstandingly efficient in enhancing perovskite quality, photovoltaic performance, and stability of perovskite solar cells (PSCs). In this work, an effective approach is applied by coupling the antisolvent mixture and multi-functional additive procedures, which is recognized as antisolvent additive engineering (AAE). The graphene quantum dots functionalized with amide (AGQDs), which consists of carbonyl, amine, and long hydrophobic alkyl chain functional groups, are added to the antisolvent mixture of toluene (T) and hexane (H) as an efficient additive to form the CH3NH3PbI3 (MAPI):AGQDs graded heterojunction structure. A broad range of analytical techniques, including scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, space charge limited current, UV-visible spectroscopy, external quantum efficiency, and time-of-flight secondary ion mass spectrometry, are used to investigate the effect of AAE treatment with AGQDs on the quality of perovskite film and performance of the PSCs. Importantly, not only a uniform and dense perovskite film with hydrophobic property is obtained but also defects on the perovskite surface are significantly passivated by the interaction between AGQDs and uncoordinated Pb2+. As a result, an enhanced power conversion efficiency (PCE) of 19.10% is achieved for the champion PSCs treated with AGQD additive, compared to the PCE of 16.00% for untreated reference PSCs. In addition, the high-efficiency PSCs based on AGQDs show high stability and maintain 89% of their initial PCE after 960 h in ambient conditions.
Fulltext The role of worm infestation in allergic rhinitis

Manuel AM, Kuljit S, Gopalakrishnan G, Suresh KG, Balraj P

Trop Biomed, 2012 Sep;29(3):360-5.
PMID: 23018498 MyJurnal

The purpose of this study is to determine the relevance of the hygiene hypothesis; that is to determine if worm infestation has a protective role against the development of allergic rhinitis. A prospective case controlled study was conducted. Specific IgG levels to Toxocara were studied in 85 patients confirmed to have allergic rhinitis and were compared to levels in another 85 controls, with no form of allergy. The IgG assay was done using ELISA technique. There was a higher incidence of positive specific IgG to Toxocara in the controls as compared to allergic patients. The values were statistically significant [Chi square test (p=0.002)]. This negative association between worm infestation and allergic rhinitis suggests that a previous worm infestation could protect against the development of allergic rhinitis.
Fulltext COVID-19-associated mucormycosis: Evidence-based critical review of an emerging infection burden during the pandemic's second wave in India

Aranjani JM, Manuel A, Abdul Razack HI, Mathew ST

PLoS Negl Trop Dis, 2021 Nov;15(11):e0009921.
PMID: 34793455 DOI: 10.1371/journal.pntd.0009921

Coronavirus Disease 2019 (COVID-19), during the second wave in early 2021, has caused devastating chaos in India. As daily infection rates rise alarmingly, the number of severe cases has increased dramatically. The country has encountered health infrastructure inadequacy and excessive demand for hospital beds, drugs, vaccines, and oxygen. Adding more burden to such a challenging situation, mucormycosis, an invasive fungal infection, has seen a sudden surge in patients with COVID-19. The rhino-orbital-cerebral form is the most common type observed. In particular, approximately three-fourths of them had diabetes as predisposing comorbidity and received corticosteroids to treat COVID-19. Possible mechanisms may involve immune and inflammatory processes. Diabetes, when coupled with COVID-19-induced systemic immune change, tends to cause decreased immunity and an increased risk of secondary infections. Since comprehensive data on this fatal opportunistic infection are evolving against the backdrop of a major pandemic, prevention strategies primarily involve managing comorbid conditions in high-risk groups. The recommended treatment strategies primarily included surgical debridement and antifungal therapy using Amphotericin B and selected azoles. Several India-centric clinical guidelines have emerged to rightly diagnose the infection, characterise the clinical presentation, understand the pathogenesis involved, and track the disease course. Code Mucor is the most comprehensive one, which proposes a simple but reliable staging system for the rhino-orbital-cerebral form. A staging system has recently been proposed, and a dedicated registry has been started. In this critical review, we extensively analyse recent evidence and guidance on COVID-19-associated mucormycosis in India.
Fulltext Biotic and abiotic variables influencing plant litter breakdown in streams: a global study

Boyero L, Pearson RG, Hui C, Gessner MO, Pérez J, Alexandrou MA, et al.

Proc Biol Sci, 2016 Apr 27;283(1829).
PMID: 27122551 DOI: 10.1098/rspb.2015.2664

Plant litter breakdown is a key ecological process in terrestrial and freshwater ecosystems. Streams and rivers, in particular, contribute substantially to global carbon fluxes. However, there is little information available on the relative roles of different drivers of plant litter breakdown in fresh waters, particularly at large scales. We present a global-scale study of litter breakdown in streams to compare the roles of biotic, climatic and other environmental factors on breakdown rates. We conducted an experiment in 24 streams encompassing latitudes from 47.8° N to 42.8° S, using litter mixtures of local species differing in quality and phylogenetic diversity (PD), and alder (Alnus glutinosa) to control for variation in litter traits. Our models revealed that breakdown of alder was driven by climate, with some influence of pH, whereas variation in breakdown of litter mixtures was explained mainly by litter quality and PD. Effects of litter quality and PD and stream pH were more positive at higher temperatures, indicating that different mechanisms may operate at different latitudes. These results reflect global variability caused by multiple factors, but unexplained variance points to the need for expanded global-scale comparisons.
Biodiversity of leaf litter fungi in streams along a latitudinal gradient

Seena S, Bärlocher F, Sobral O, Gessner MO, Dudgeon D, McKie BG, et al.

Sci Total Environ, 2019 Apr 15;661:306-315.
PMID: 30677678 DOI: 10.1016/j.scitotenv.2019.01.122

Global patterns of biodiversity have emerged for soil microorganisms, plants and animals, and the extraordinary significance of microbial functions in ecosystems is also well established. Virtually unknown, however, are large-scale patterns of microbial diversity in freshwaters, although these aquatic ecosystems are hotspots of biodiversity and biogeochemical processes. Here we report on the first large-scale study of biodiversity of leaf-litter fungi in streams along a latitudinal gradient unravelled by Illumina sequencing. The study is based on fungal communities colonizing standardized plant litter in 19 globally distributed stream locations between 69°N and 44°S. Fungal richness suggests a hump-shaped distribution along the latitudinal gradient. Strikingly, community composition of fungi was more clearly related to thermal preferences than to biogeography. Our results suggest that identifying differences in key environmental drivers, such as temperature, among taxa and ecosystem types is critical to unravel the global patterns of aquatic fungal diversity.
Fulltext Riparian plant litter quality increases with latitude

Boyero L, Graça MAS, Tonin AM, Pérez J, J Swafford A, Ferreira V, et al.

Sci Rep, 2017 09 05;7(1):10562.
PMID: 28874830 DOI: 10.1038/s41598-017-10640-3

Plant litter represents a major basal resource in streams, where its decomposition is partly regulated by litter traits. Litter-trait variation may determine the latitudinal gradient in decomposition in streams, which is mainly microbial in the tropics and detritivore-mediated at high latitudes. However, this hypothesis remains untested, as we lack information on large-scale trait variation for riparian litter. Variation cannot easily be inferred from existing leaf-trait databases, since nutrient resorption can cause traits of litter and green leaves to diverge. Here we present the first global-scale assessment of riparian litter quality by determining latitudinal variation (spanning 107°) in litter traits (nutrient concentrations; physical and chemical defences) of 151 species from 24 regions and their relationships with environmental factors and phylogeny. We hypothesized that litter quality would increase with latitude (despite variation within regions) and traits would be correlated to produce 'syndromes' resulting from phylogeny and environmental variation. We found lower litter quality and higher nitrogen:phosphorus ratios in the tropics. Traits were linked but showed no phylogenetic signal, suggesting that syndromes were environmentally determined. Poorer litter quality and greater phosphorus limitation towards the equator may restrict detritivore-mediated decomposition, contributing to the predominance of microbial decomposers in tropical streams.
Fulltext Global Retinoblastoma Presentation and Analysis by National Income Level

Global Retinoblastoma Study Group, Fabian ID, Abdallah E, Abdullahi SU, Abdulqader RA, Adamou Boubacar S, et al.

JAMA Oncol, 2020 May 01;6(5):685-695.
PMID: 32105305 DOI: 10.1001/jamaoncol.2019.6716

IMPORTANCE: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale.
OBJECTIVES: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis.
DESIGN, SETTING, AND PARTICIPANTS: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017.
MAIN OUTCOMES AND MEASURES: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis.
RESULTS: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]).
CONCLUSIONS AND RELEVANCE: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.