Cleaning Up without Messing Up: Maximizing the Benefits of Plastic Clean-Up Technologies through New Regulatory Approaches.

As the global plastics crisis grows, numerous technologies have been invented and implemented to recover plastic pollution from the environment. Although laudable, unregulated clean-up technologies may be inefficient and have unintended negative consequences on ecosystems, for example, through bycatch or removal of organic matter important for ecosystem functions. Despite these concerns, plastic clean-up technologies can play an important role in reducing litter in the environment. As the United Nations Environment Assembly is moving toward an international, legally binding treaty to address plastic pollution by 2024, the implementation of plastic clean-up technologies should be regulated to secure their net benefits and avoid unintended damages. Regulation can require environmental impact assessments and life cycle analysis to be conducted predeployment on a case-by-case basis to determine their effectiveness and impact and secure environmentally sound management. During operations catch-efficiency and bycatch of nonlitter items, as well as waste management of recovered litter, should be documented. Data collection for monitoring, research, and outreach to mitigate plastic pollution is recommended as added value of implementation of clean-up technologies.

A comprehensive assessment of plastic remediation technologies.

The global presence of plastic litter and its accumulation in the environment has become an issue of concern to the public and policymakers. This concern has triggered innovators in past decades to design and develop a multitude of remediation technologies to prevent plastic from entering the environment, or to clean up legacy litter. This study aims to (i) systematically review the current scientific literature on plastic remediation technologies, (ii) create a 'plastic clean-up and prevention overview' illustrating 124 remediation technologies and 29 characteristics, (iii) qualitatively analyse their key characteristics (e.g., fields of application, targeted plastic), and (iv) investigate challenges and opportunities of clean-up technologies for inland waterways (e.g., canals, rivers) and ports. We identified 61 scientific publications on plastic remediation technologies, until June 2022. Thirty-four of these studies were published within the last three years, demonstrating a growing interest. The presented overview indicates that inland waterways are, so far, the preferred field of application, with 22 technologies specifically designed for cleaning up plastics from inland waterways, and 52 additional ones with the potential to be installed in these locations. Given the importance of clean-up technologies in inland waterways, we highlighted their strengths, weaknesses, opportunities, and threats (SWOT). Our results indicate that, despite the challenges, these technologies provide essential prospects, from improving the environmental quality to raising awareness. Our study is instrumental as it illustrates an up-to-date overview and provides a comprehensive analysis of current in design phase, testing, and in use plastic remediation technologies.

Integrating Bayesian Belief Networks in a toolbox for decision support on plastic clean-up technologies in rivers and estuaries.

Current mitigation strategies to offset marine plastic pollution, a global concern, typically rely on preventing floating debris from reaching coastal ecosystems. Specifically, clean-up technologies are designed to collect plastics by removing debris from the aquatic environment such as rivers and estuaries. However, to date, there is little published data on their potential impact on riverine and estuarine organisms and ecosystems. Multiple parameters might play a role in the chances of biota and organic debris being unintentionally caught within a mechanical clean-up system, but their exact contribution to a potential impact is unknown. Here, we identified four clusters of parameters that can potentially determine the bycatch: (i) the environmental conditions in which the clean-up system is deployed, (ii) the traits of the biota the system interacts with, (iii) the traits of plastic items present in the system, and, (iv) the design and operation of the clean-up mechanism itself. To efficiently quantify and assess the influence of each of the clusters on bycatch, we suggest the use of transparent and objective tools. In particular, we discuss the use of Bayesian Belief Networks (BBNs) as a promising probabilistic modelling method for an evidence-based trade-off between removal efficiency and bycatch. We argue that BBN probabilistic models are a valuable tool to assist stakeholders, prior to the deployment of any clean-up technology, in selecting the best-suited mechanism to collect floating plastic debris while managing potential adverse effects on the ecosystem.

Adjunctive Clotiapine for the Management of Delusions in Two Adolescents with Anorexia Nervosa.

Clotiapine is an atypical antipsychotic indicated for the management of a series of acute psychotic disorders. The current literature lacks evidence concerning the tolerability and clinical use of this drug in the management of individuals with anorexia nervosa (AN). In this study, we report two cases of adolescents with AN, treated with clotiapine. The reason for the administration of clotiapine was, for both patients, the manifestation of bizarre delusions concerning food and calories. Patient 1 presented a presyncope after the first dose of clotiapine, and treatment was rapidly discontinued. Patient 2 was treated with clotiapine for 9 months; doses were titrated from 20 mg/day to 70 mg/day, with an improvement in the reported delusions, which also enhanced compliance with psychological and nutritional interventions. EKG, QTc, white blood count, and red blood count were not relevantly influenced by the introduction of clotiapine in either patient. No extrapyramidal effect was documented. These reports stress the need for further studies assessing the tolerability and potential effect of clotiapine in treating adolescents with AN and delusional symptomatology.

Patterns of ectoparasite infection in wild-caught and laboratory-bred cichlid fish, and their hybrids, implicate extrinsic rather than intrinsic causes of species differences in infection.

Parasite-mediated selection may initiate or enhance differentiation between host populations that are exposed to different parasite infections. Variation in infection among populations may result from differences in host ecology (thereby exposure to certain parasites) and/or intrinsic immunological traits. Species of cichlid fish, even when recently diverged, often differ in parasite infection, but the contributions of intrinsic and extrinsic causes are unknown. Here, we compare infection patterns between two closely related host species from Lake Victoria (genus Pundamilia), using wild-caught and first-generation laboratory-reared fish, as well as laboratory-reared hybrids. Three of the commonest ectoparasite species observed in the wild were also present in the laboratory populations. However, the infection differences between the host species as observed in the wild were not maintained in laboratory conditions. In addition, hybrids did not differ in infection from either parental species. These findings suggest that the observed species differences in infection in the wild might be mainly driven by ecology-related effects (i.e. differential exposure), rather than by intrinsic species differences in immunological traits. Thus, while there is scope for parasite-mediated selection in Pundamilia in the wild, it has apparently not yet generated divergent evolutionary responses and may not enhance assortative mating among closely related species.

ELP2 compound heterozygous variants associated with cortico-cerebellar atrophy, nodular heterotopia and epilepsy: Phenotype expansion and review of the literature.

The elongator complex is a highly conserved macromolecular assembly composed by 6 individual proteins (Elp 1-6) and it is essential for many cellular functions such as transcription elongation, histone acetylation and tRNA modification. ELP2 is the second major subunit and with Elp1 and Elp3 it shapes the catalytic core of this essential complex. ELP2 gene pathogenic variants have been reported to be associated with several neurodevelopmental disorders, such as intellectual disability, severe motor development delay with truncal hypotonia, spastic diplegia, choreoathetosis, short stature and neuropsychiatric problems. Here we report a case with heterozygous variants of the ELP2 gene associated with unpublished electro-clinical and neuroimaging features, such as abnormal eye movements, focal epilepsy, cortico-cerebellar atrophy and nodular cortical heterotopia on brain MRI. A possible phenotype-genotype correlation and the electro-clinical and neuroimaging phenotype expansion of ELP2 mutations are here discussed, together with considerations on involved cortico-cerebellar networks and a detailed review of the literature.

Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses.

Converting carcinomas in benign oncocytomas has been suggested as a potential anti-cancer strategy. One of the oncocytoma hallmarks is the lack of respiratory complex I (CI). Here we use genetic ablation of this enzyme to induce indolence in two cancer types, and show this is reversed by allowing the stabilization of Hypoxia Inducible Factor-1 alpha (HIF-1α). We further show that on the long run CI-deficient tumors re-adapt to their inability to respond to hypoxia, concordantly with the persistence of human oncocytomas. We demonstrate that CI-deficient tumors survive and carry out angiogenesis, despite their inability to stabilize HIF-1α. Such adaptive response is mediated by tumor associated macrophages, whose blockage improves the effect of CI ablation. Additionally, the simultaneous pharmacological inhibition of CI function through metformin and macrophage infiltration through PLX-3397 impairs tumor growth in vivo in a synergistic manner, setting the basis for an efficient combinatorial adjuvant therapy in clinical trials.

The Oncojanus Paradigm of Respiratory Complex I.

Mitochondrial respiratory function is now recognized as a pivotal player in all the aspects of cancer biology, from tumorigenesis to aggressiveness and chemotherapy resistance. Among the enzymes that compose the respiratory chain, by contributing to energy production, redox equilibrium and oxidative stress, complex I assumes a central role. Complex I defects may arise from mutations in mitochondrial or nuclear DNA, in both structural genes or assembly factors, from alteration of the expression levels of its subunits, or from drug exposure. Since cancer cells have a high-energy demand and require macromolecules for proliferation, it is not surprising that severe complex I defects, caused either by mutations or treatment with specific inhibitors, prevent tumor progression, while contributing to resistance to certain chemotherapeutic agents. On the other hand, enhanced oxidative stress due to mild complex I dysfunction drives an opposite phenotype, as it stimulates cancer cell proliferation and invasiveness. We here review the current knowledge on the contribution of respiratory complex I to cancer biology, highlighting the double-edged role of this metabolic enzyme in tumor progression, metastasis formation, and response to chemotherapy.

Unravelling the Effects of the Mutation m.3571insC/MT-ND1 on Respiratory Complexes Structural Organization.

Mammalian respiratory complex I (CI) biogenesis requires both nuclear and mitochondria-encoded proteins and is mostly organized in respiratory supercomplexes. Among the CI proteins encoded by the mitochondrial DNA, NADH-ubiquinone oxidoreductase chain 1 (ND1) is a core subunit, evolutionary conserved from bacteria to mammals. Recently, ND1 has been recognized as a pivotal subunit in maintaining the structural and functional interaction among the hydrophilic and hydrophobic CI arms. A critical role of human ND1 both in CI biogenesis and in the dynamic organization of supercomplexes has been depicted, although the proof of concept is still missing and the critical amount of ND1 protein necessary for a proper assembly of both CI and supercomplexes is not defined. By exploiting a unique model in which human ND1 is allotopically re-expressed in cells lacking the endogenous protein, we demonstrated that the lack of this protein induces a stall in the multi-step process of CI biogenesis, as well as the alteration of supramolecular organization of respiratory complexes. We also defined a mutation threshold for the m.3571insC truncative mutation in mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1), below which CI and its supramolecular organization is recovered, strengthening the notion that a certain amount of human ND1 is required for CI and supercomplexes biogenesis.

Mild phenotypes and proper supercomplex assembly in human cells carrying the homoplasmic m.15557G > A mutation in cytochrome b gene.

Respiratory complex III (CIII) is the first enzymatic bottleneck of the mitochondrial respiratory chain both in its native dimeric form and in supercomplexes. The mammalian CIII comprises 11 subunits among which cytochrome b is central in the catalytic core, where oxidation of ubiquinol occurs at the Qo site. The Qo- or PEWY-motif of cytochrome b is the most conserved through species. Importantly, the highly conserved glutamate at position 271 (Glu271) has never been studied in higher eukaryotes so far and its role in the Q-cycle remains debated. Here, we showed that the homoplasmic m.15557G > A/MT-CYB, which causes the p.Glu271Lys amino acid substitution predicted to dramatically affect CIII, induces a mild mitochondrial dysfunction in human transmitochondrial cybrids. Indeed, we found that the severity of such mutation is mitigated by the proper assembly of CIII into supercomplexes, which may favor an optimal substrate channeling and buffer superoxide production in vitro.

Platinum-induced mitochondrial DNA mutations confer lower sensitivity to paclitaxel by impairing tubulin cytoskeletal organization.

Development of chemoresistance is a cogent clinical issue in oncology, whereby combination of anticancer drugs is usually preferred also to enhance efficacy. Paclitaxel (PTX), combined with carboplatin, represents the standard first-line chemotherapy for different types of cancers. We here depict a double-edge role of mitochondrial DNA (mtDNA) mutations induced in cancer cells after treatment with platinum. MtDNA mutations were positively selected by PTX, and they determined a decrease in the mitochondrial respiratory function, as well as in proliferative and tumorigenic potential, in terms of migratory and invasive capacity. Moreover, cells bearing mtDNA mutations lacked filamentous tubulin, the main target of PTX, and failed to reorient the Golgi body upon appropriate stimuli. We also show that the bioenergetic and cytoskeletal phenotype were transferred along with mtDNA mutations in transmitochondrial hybrids, and that this also conferred PTX resistance to recipient cells. Overall, our data show that platinum-induced deleterious mtDNA mutations confer resistance to PTX, and confirm what we previously reported in an ovarian cancer patient treated with carboplatin and PTX who developed a quiescent yet resistant tumor mass harboring mtDNA mutations.

The α-ketoglutarate dehydrogenase complex in cancer metabolic plasticity.

Deregulated metabolism is a well-established hallmark of cancer. At the hub of various metabolic pathways deeply integrated within mitochondrial functions, the α-ketoglutarate dehydrogenase complex represents a major modulator of electron transport chain activity and tricarboxylic acid cycle (TCA) flux, and is a pivotal enzyme in the metabolic reprogramming following a cancer cell's change in bioenergetic requirements. By contributing to the control of α-ketoglutarate levels, dynamics, and oxidation state, the α-ketoglutarate dehydrogenase is also essential in modulating the epigenetic landscape of cancer cells. In this review, we will discuss the manifold roles that this TCA enzyme and its substrate play in cancer.

Heart rate affects endothelial function in essential hypertension.

Increased heart rate (HR) is a risk factor for cardiovascular morbidity and mortality in the general population and in some clinical conditions. Endothelial dysfunction is an adverse prognostic factor for cardiovascular events. The aim of the study was to evaluate the effect of HR on central hemodynamic parameters and endothelial function in hypertension. We evaluated forearm blood flow (FBF) response to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) in 30 patients with HR ≤60 min(-1) and 30 with HR ≥80 min(-1). The FBF was measured by strain-gauge plethysmography. Transesophageal atrial pacing was used to increase the HR. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressures and correlate hemodynamic indices. The FBF response to ACh is lower in hypertensives with HR ≤60 min(-1) than in those with HR ≥80 min(-1) (10.6 ± 4.2 vs. 13.6 ± 5.1 ml × 100 ml(-1) of tissue × min(-1), P < 0.001). Vascular resistance decreases to 9.3 ± 2.8 U in patients with lower HR versus 7.2 ± 2.1 U in those with higher HR (P = 0.002). The FBF response to SNP is similar in both groups. Central systolic and pulse pressure are higher in bradycardic patients than in those with HR ≥80 min(-1) (140 ± 8 vs. 131 ± 8 mmHg, P = 0.0001 and 49 ± 10 vs. 39 ± 11 mmHg, P = 0.0001). All central hemodynamic parameters decrease during incremental atrial pacing. Augmentation index is the strongest predictor of endothelial dysfunction at multivariate analysis. These findings demonstrate that low HR affects endothelium-dependent vasodilation in hypertension. Increased central aortic pressure and hemodynamic correlates seem to be the underlying mechanisms by which bradycardia interferes with endothelium-dependent reactivity.

Association between hemoglobin level and endothelial function in uncomplicated, untreated hypertensive patients.

BACKGROUND AND OBJECTIVES: Hemoglobin (Hb) is an important nitric oxide (NO) buffer and a modulator of NO bioavailability. In addition, endothelial dysfunction is common in hypertensive patients, suggesting a pivotal role of hemoglobin concentration ([Hb]) in vascular function. To investigate the potential role of [Hb] in endothelium-dependent vasodilation, the relationship between Hb and endothelial function was tested in a group of patients with essential hypertension. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective study, 174 nonsmoking, uncomplicated, never-treated hypertensives were enrolled. Endothelium-dependent and -independent vasodilation was assessed by measurement of forearm blood flow response during intra-arterial infusion of increasing doses of acetylcholine (ACh) and sodium nitroprusside (SNP) using strain-gauge plethysmography. Correlation with established risk factors of endothelial dysfunction was performed. RESULTS: The vasodilatory response to ACh was inversely (P < 0.001) related to [Hb], and this relationship was dose dependent (P < 0.001), being minimal at the lowest dose and maximal at the highest dose. No association was found between Hb and the vasodilatory response to SNP. In a multiple linear regression model adjusted for Framingham risk factors (age, sex, BP, cholesterol, body mass index, glucose) and emerging risk factors (homeostasis model assessment index, C-reactive protein, estimated GFR), [Hb] maintained a strong and independent link with the vasodilatory response to ACh (P < 0.001). CONCLUSIONS: In a large group of nonsmoking untreated hypertensives, [Hb] is inversely related to forearm endothelium-dependent vasodilation. [Hb] should be taken into account, especially in conditions associated with low [Hb], when performing vascular function studies.

Endothelial dysfunction, ADMA and insulin resistance in essential hypertension.

BACKGROUND: Endothelial dysfunction and insulin resistance (IR) are associated with essential hypertension and other cardiovascular risk factors. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, induces endothelial dysfunction in different setting of patients. However, at this moment no data are available about the role of ADMA and IR to induce endothelial dysfunction in an independent way or combined between them. In this study, we investigated, in 63 hypertensives and 21 normotensive healthy subjects, the relationship between ADMA and IR and their possible interaction on endothelial function. METHODS: ADMA plasma levels were measured by high-performance liquid chromatography, and IR by homeostasis model assessment (HOMA). Endothelial function was estimated by intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside at increasing doses. RESULTS: Hypertensive patients had significantly higher ADMA, insulin, HOMA and C-reactive protein (CRP) values than normotensive controls (P<0.0001). There were no significant differences in mean l-arginine/ADMA ratio between groups. ACh-stimulated forearm blood flow (FBF) was significantly reduced in hypertensive patients (P<0.0001). In hypertensive group, HOMA was the strongest determinant of FBF, accounting for the 45.5% of its variation. ADMA and gender were the independent determinants of HOMA, accounting for 12.3% and 8.3% of its variation, respectively. CONCLUSIONS: The association between ADMA and IR contributes to identify a possible novel mechanism by which ADMA promotes vascular damage, increasing individual cardiovascular risk in hypertensive patients. However, this hypothesis should be tested in a larger study group.

Renal function predicts cardiovascular outcomes in southern Italian postmenopausal women.

BACKGROUND: Postmenopausal women have an increased risk of adverse cardiovascular (CV) events. Similarly, chronic kidney disease (CKD) is a well established risk factor for CV disease and mortality. DESIGN: We evaluated the effect of renal function on the risk of death and CV events in 1500 southern Italian postmenopausal women. METHODS AND RESULTS: Renal function was estimated (e) by glomerular filtration rate (e-GFR) by Modification of Diet in Renal Disease equation. We classified postmenopausal women in two groups of e-GFR (ml/min per 1.73 m(2)): > or =60 (group 1) and less than 60 (group 2). The primary endpoint was major adverse CV events (MACE). The secondary endpoints were total events (MACE + death from any cause), coronary events, and stroke. During the follow-up (mean=72.6 months), there were 200 new CV morbid events. The rate of MACE (per 100 patient-years) was 1.88 and 2.98 in the two groups of e-GFR (P<0.0001). On univariate analysis, the incident risk of CV events was inversely related with the e-GFR values; similarly, in multiple Cox regression model, only the e-GFR maintained an independent association with MACE and secondary end-points. CONCLUSION: For the first time, we demonstrated that the reduction of e-GFR was associated with the increased risk of death and CV events, independently of traditional CV risk factors, menopause duration, and presence of metabolic syndrome.

Low-plasma insulin-like growth factor-I levels are associated with impaired endothelium-dependent vasodilatation in a cohort of untreated, hypertensive Caucasian subjects.

CONTEXT: Accumulating evidence suggests that IGF-I has protective vascular effects, supporting the possibility that IGF-I deficiency may contribute to atherosclerosis. However, the relationship between plasma IGF-I levels and endothelium-dependent vasodilatation is still unsettled. OBJECTIVE: We designed this present study to test the hypothesis that low-plasma IGF-I levels are associated with reduced endothelial function independently classical cardiovascular risk factors. SETTING: Outpatients were included in the study. PATIENTS: A total of 100 never-treated hypertensive Caucasian subjects participating in the CAtanzaro MEtabolic RIsk factors Study was recruited. INTERVENTIONS: Subjects underwent forearm blood flow (FBF) evaluation by strain-gauge plethysmography in response to increasing doses of acetylcholine (ACh) (Sigma, Milan, Italy) and sodium nitroprusside (Malesci, Florence, Italy). Insulin sensitivity was estimated by the homeostasis model assessment index. RESULTS: Plasma IGF-I levels were significantly correlated with age (r = -0.300; P = 0.001), high-density lipoprotein serum cholesterol (r = 0.211; P = 0.017), homeostasis model assessment index (r = -0.355; P <0.0001), systolic blood pressure (r = -0.174; P = 0.042), glomerular filtration rate (r = 0.228; P = 0.011), and ACh-stimulated FBF (r = 0.565; P <0.0001). In a stepwise forward multivariate regression analysis, the strongest predictors of ACh-stimulated FBF response were plasma IGF-I levels, accounting for 31.9% of its variation. CONCLUSIONS: These results demonstrate, for the first time, that low-plasma IGF-I levels are highly associated with reduced endothelial function, an early step in atherogenesis process.