Visceral Obesity and Its Shared Role in Cancer and Cardiovascular Disease: A Scoping Review of the Pathophysiology and Pharmacological Treatments

The association between obesity, cancer and cardiovascular disease (CVD) has been demonstrated in animal and epidemiological studies. However, the specific role of visceral obesity on cancer and CVD remains unclear. Visceral adipose tissue (VAT) is a complex and metabolically active tissue, that can produce different adipokines and hormones, responsible for endocrine-metabolic comorbidities. This review explores the potential mechanisms related to VAT that may also be involved in cancer and CVD. In addition, we discuss the shared pharmacological treatments which may reduce the risk of both diseases. This review highlights that chronic inflammation, molecular aspects, metabolic syndrome, secretion of hormones and adiponectin associated to VAT may have synergistic effects and should be further studied in relation to cancer and CVD. Reductions in abdominal and visceral adiposity improve insulin sensitivity, lipid profile and cytokines, which consequently reduce the risk of CVD and some cancers. Several medications have shown to reduce visceral and/or subcutaneous fat. Further research is needed to investigate the pathophysiological mechanisms by which visceral obesity may cause both cancer and CVD. The role of visceral fat in cancer and CVD is an important area to advance. Public health policies to increase public awareness about VAT’s role and ways to manage or prevent it are needed.     

Grid current regulation of a three-phase voltage source inverter with an LCL input filter

Many grid connected power electronic systems, such as STATCOMs, UPFCs, and distributed generation system interfaces, use a voltage source inverter (VSI) connected to the supply network through a filter. This filter, typically a series inductance, acts to reduce the switching harmonics entering the distribution network. An alternative filter is a LCL network, which can achieve reduced levels of harmonic distortion at lower switching frequencies and with less inductance, and therefore has potential benefits for higher power applications. However, systems incorporating LCL filters require more complex control strategies and are not commonly presented in literature. This paper proposes a robust strategy for regulating the grid current entering a distribution network from a three-phase VSI system connected via a LCL filter. The strategy integrates an outer loop grid current regulator with inner capacitor current regulation to stabilize the system. A synchronous frame PI current regulation strategy is used for the outer grid current control loop. Linear analysis, simulation, and experimental results are used to verify the stability of the control algorithm across a range of operating conditions. Finally, expressions for ""harmonic impedance" of the system are derived to study the effects of supply voltage distortion on the harmonic performance of the system.     

Effect of preparation technique on the properties of Mo-containing Al-MCM-41

The Al-MCM-41 has been used as support to prepare Mo-containing catalysts. The 12- molybdophosphoric heteropoly acid (HPMo) is used as initial compound. The catalysts are synthesized by two different methods: incipient impregnation with aqueous solution of the acid and mechanochemical synthesis. The samples were tested in the reaction of the thiophene hydrodesulfurization after activation with mixture H₂ + H₂S. The effect of the preparation method of the catalysts on their physicochemical and catalytic properties has been studied. A partial destruction of the loaded compound is observed in mechanochemically treated sample whereas the aggregates are formed from the particles of different size in the impregnated sample. The specific surface area of the sample prepared by mechanical–chemical treatment decreases 2–3 times, while the total pore volume is about four times lower. The HDS activity is higher on the impregnated sample than on the mechanochemically treated one.     

Input to verb learning: Evidence for the plausibility of syntactic bootstrapping.

The theory of syntactic bootstrapping proposes that children use the syntactic frames in which verbs are presented as a source of information about their meaning. The purpose of this study was to investigate the extent to which maternal type and diversity of verb frames are consistent with the requirements of that theory. The uses of 25 common verbs in the speech of 57 mothers to their 1- to 2-year-old children were tabulated and parsed for syntactic frame. Analyses revealed 2 major findings concerning the use of verbs in child-directed speech: (a) Verbs in different semantic categories appear in different syntactic environments, and (b) individual verbs are distinguished by the set of frames in which they appear. These findings support the plausibility of the syntactic bootstrapping hypothesis by demonstrating that children's input provides the structural cues to verb meaning that the syntactic bootstrapping procedure requires. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Some teachings from the history of social psychology.

Explores several questions relating to historical inquiry in the field of social psychology. During its Golden Age, 1945–1970, social psychology was busy defining different fields and paradigms, building theories, and verifying hypotheses; there was little time and need for reflection. The 1970s saw an era of doubts, critique and crisis, during which the constituted knowledge bases were undermined on a number of fronts: methodological, ethical, and theoretical. Examples of how critical history may serve a heuristic function for social psychology are given. The question of how to conduct historical inquiry is addressed, even for as problematic an object as social psychology's development in France. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Distribution and Fate of Escherichia coli in Lake Michigan Following Contamination with Urban Stormwater and Combined Sewer Overflows

Escherichia coli distribution and persistence in nearshore Lake Michigan were assessed following heavy rains and sanitary sewer overflow (SSO) and combined sewer overflow (CSO) events over a 5-year period, including an 18-day period following 25.4 cm of rainfall in which intensive studies were conducted following multiple CSO and SSO events. E. coli levels in the Milwaukee estuary and harbor following SSO and CSO events ranged from 10⁴ to nearly 10⁵ CFU/100 mL, which were significantly higher (p ≤ 0.05) than levels following rainfall alone. Sites outside of the breakwall but within the contamination plume (e.g., within 2 km of the harbor) were an order of magnitude lower. Locations 2–5 km from the harbor ranged from below detection limits, of < 1 to 5 CFU/100 mL. E. coli levels corrected for dilution based on specific conductivity measurements were lower than what would be expected for loss due to dilution alone, suggesting a combination of die-off and dilution, were responsible for the rapid disappearance of these organisms outside of the harbor. E. coli and fecal coliforms measured concurrently demonstrated that fecal coliforms could be recovered longer than E. coli in the open waters of the lake. E. coli isolated directly from sewage treatment plant influent were found to have a marked increase in antibiotic resistance traits for ten antibiotics commonly used in the human population compared with isolates from two animal sources of fecal pollution. However, E. coli obtained from sewage impacted water (n = 2,513) and from stormwater impacted water (n = 1,465) collected the previous year when there were no sewage overflows, were found to have no significant difference (p < 0.05) in the frequency of resistance when comparing the two conditions. E. coli survival characteristics and population dynamics are most likely influenced by multiple factors in complex systems such as the watershed/estuarine/lake environments of the Great Lakes.     

Biflavonoid-Induced Disruption of Hydrogen Bonds Leads to Amyloid-β Disaggregation

Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC₅₀ values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease.     

Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors

HER2 targeted therapies have significantly improved prognosis of HER2-positive breast and gastric cancer. HER2 overexpression and mutation is the pathogenic driver in non-small cell lung cancer (NSCLC) and colorectal cancer, however, to date, there are no approved HER2-targeted therapies with these indications. Trastuzumab deruxtecan (T-DXd) is a novel HER2-directed antibody drug conjugate showing significant anti-tumor activity in heavily pre-treated HER2-positive breast and gastric cancer patients. Preliminary data have shown promising objective response rates in patients with HER2-positive NSCLC and colorectal cancer. T-DXd has an acceptable safety profile, however with concerns regarding potentially serious treatment-emergent adverse events. In this review we focus on the pharmacologic characteristics and toxicity profile of T-Dxd, and provide an update on the most recent results of clinical trials of T-DXd in solid tumors. The referenced papers were selected through a PubMed search performed on 16 March 2021 with the following searching terms: T-DXd and breast cancer, or gastric cancer, or non-small cell lung cancer (NSCLC), or colorectal cancer. Oral presentation, abstracts, and posters presented at the American Society of Clinical Oncology (ASCO, Alexandria, VA, USA) 2020 and the European Society for Medical Oncology (ESMO, Lugano, Switzerland) 2020 annual meetings were retrieved for data on T-DXd. We also overview ongoing research and data of combination therapies currently under investigation, which will impact on future therapeutic strategies. Clinicaltrials.gov was searched to identify ongoing clinical trials of T-DXd alone or in combination in solid tumors.