Temperature and Frequency Dependence of Magnetic Losses in Fe-Co

We investigate the temperature dependence of the energy loss W(f) of 0.10 and 0.20 mm thick Fe-Co-V sheets (Vacoflux (R) and Vacodur (R)) in the range-50(degrees)C <= T <= 155(degrees)C. The measurements, performed from DC to f = 5 kHz on ring samples and Epstein strips, show that W(f) passes through a minimum value around room temperature at all tested polarization values (1.0 <= J(p) <= 1.9 T). The largest effect occurs under quasi-static regime and declines with frequency, depending on the sheet thickness and the ensuing role of the dynamic loss. The somewhat abnormal increase of the quasi-static loss W-hyst with temperature, which contrasts with a concurrent decrease of the magneto crystalline anisotropy constant, is interpreted in terms of temperature-dependent internal stresses and their change with T. The stresses are assumed to derive from the different thermal expansion coefficients of the ordered and disordered structural phases, a conclusion made plausible by the highly magnetostrictive properties of the material, dwelling in a low anisotropy environment. The AC properties are treated by adapting the loss decomposition to the inception and development of a non-uniform induction profile across the sheet thickness (skin effect) at high frequencies. The classical loss component is calculated via the numerical solution of the Maxwell's diffusion equation, where the magnetic constitutive equation of the material is identified with the normal magnetization curve. It turns out that the so-found W-class(f) and the resulting excess loss W-exc(f) are moderately dependent on temperature and W(f) eventually tends towards a slow monotonical decrease with Tat the highest frequencies

Discovery of Bile Acid Derivatives as Potent ACE2 Activators by Virtual Screening and Essential Dynamics

The angiotensin-converting enzyme II (ACE2) is a key molecular player in the regulation of vessel contraction, inflammation, and reduction of oxidative stress. In addition, ACE2 has assumed a prominent role in the fight against the COVID-19 pandemic-causing virus SARS-CoV-2, as it is the very first receptor in the host of the viral spike protein. The binding of the spike protein to ACE2 triggers a cascade of events that eventually leads the virus to enter the host cell and initiate its life cycle. At the same time, SARS-CoV-2 infection downregulates ACE2 expression especially in the lung, altering the biochemical signals regulated by the enzyme and contributing to the poor clinical prognosis characterizing the late stage of the COVID-19 disease. Despite its important biological role, a very limited number of ACE2 activators are known. Here, using a combined in silico and experimental approach, we show that ursodeoxycholic acid (UDCA) derivatives work as ACE2 activators. In detail, we have identified two potent ACE2 ligands, BAR107 and BAR708, through a docking virtual screening campaign and elucidated their mechanism of action from essential dynamics of the enzyme observed during microsecond molecular dynamics calculations. The in silico results were confirmed by in vitro pharmacological assays with the newly identified compounds showing ACE2 activity comparable to that of DIZE, the most potent ACE2 activator known so far. Our work provides structural insight into ACE2/ligand-binding interaction useful for the design of compounds with therapeutic potential against SARS-CoV-2 infection, inflammation, and other ACE2-related diseases

Discovery of a Potent and Orally Active Dual GPBAR1/CysLT1R Modulator for the Treatment of Metabolic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are two highly prevalent human diseases caused by excessive fat deposition in the liver. Although multiple approaches have been suggested, NAFLD/NASH remains an unmet clinical need. Here, we report the discovery of a novel class of hybrid molecules designed to function as cysteinyl leukotriene receptor 1 (CysLT1R) antagonists and G protein bile acid receptor 1 (GPBAR1/TGR5) agonists for the treatment of NAFLD/NASH. The most potent of these compounds generated by harnessing the scaffold of the previously described CystLT1R antagonists showed efficacy in reversing liver histopathology features in a preclinical model of NASH, reshaping the liver transcriptome and the lipid and energy metabolism in the liver and adipose tissues. In summary, the present study described a novel orally active dual CysLT1R antagonist/GPBAR1 agonist that effectively protects against the development of NAFLD/NASH, showing promise for further development

Retrospective and observational study to assess the efficacy of citicoline in elderly patients suffering from stupor related to complex geriatric syndrome

A significant percentage of elderly subjects (50%–80%) suffering from sub-acute ischemic cerebrovascular disease, with or without moderate or severe cognitive memory decline and with or without associated behavioral and psychological symptoms, shows a complex syndrome. This syndrome is related to the progressive impairment of health conditions and/or stressing events (ie, hospitalization), characterized by confusion and/or stupor, which are consequently difficult to manage and require a great deal of care. Geriatric patients often suffer from multiple chronic illnesses, may take numerous medications daily, exhibit clinical instability, and may experience worsening of medical conditions following cerebral ischemic events and thus have an increased risk of disability and mortality. There are several studies in literature which demonstrate the efficacy of citicoline, thanks to its neuroprotective function, for the recovery and in postischemic cerebral rehabilitation. It has been shown that, even soon after an ischemic stroke, administration of oral citicoline (500–4000 mg/day) improves the general conditions evaluated with the Rankin scale and the National Institute of Health Stroke Scale 12. In particular, it has been shown that the CDP-choline improves the cognitive and mental performance in Alzheimer’s dementia and vascular dementia. We have evaluated the administration of citicoline in geriatric patients following a protocol of intravenous study on improvement of individual performances

Barriers in care pathways and unmet mental health needs in LGBTIQ + communities

Lesbian, gay, bisexual, transgender, intersex, queer people and minority gender identities and sexualities (LGBTIQþ) are often stigmatized and experience discrimination in health care settings, leading to poorer mental health outcomes and unmet needs compared to heterosexual and cisgendered peers. It is thus imperative that mental health providers consider and address structural challenges in order to reduce mental health inequalities of this population. This narrative review assessed the barriers that may prevent access to care and the pathways for care in LGBTIQþ communities. PubMed, PsycInfo, Embase, and Scopus were searched for papers published between December 2021 and February 2022. A total of 107 papers were included with studies reflecting five themes: (1) Unmet mental health needs; (2) Young people; (3) Substance abuse and addiction; (4) Barriers and pathways to care; and (5) Interventions. Findings demonstrate that LGBTIQþ people experience stigmatization and higher rates of substance misuse and mental ill health, which may lead to barriers in accessing health care services, and fewer tailored interventions being provided. These findings have implications for policy, health care screening, and how specialist services are structured. Substantial gaps in the evidence-base exist, and future research should examine how mental health care providers can challenge social issues that maintain discriminatory and stigmatizing practices, and support LGBTIQþ individuals to sustain their resilience

An innovative fast track solution for food bolus impaction due to Jackhammer esophagus in an emergency department: the "Nitro-Push Blind Technique" case report

Background: In the medical literature are described only few clinical cases of esophageal food bolus impaction due to esophageal motility disorders. Moreover, the management of this condition is highly variable with no evidence in the literature to strongly support a clear defined intervention.Case presentation: In this paper we describe for the first time a case of 53-year-old male with food bolus impaction due to Jackhammer esophagus referred to emergency department. On the basis of the known esophageal past medical history as well as the absence of bones in the bolus, the patient was submitted to a new conservative treatment, the "Nitro-Push Blind Technique".Conclusions: The new technique performed with naso-gastric tube thrust after nitrates medication in definite clinical case supported by known functional disease, represents a safe and successful method, with short observational period to minimize exposure to potential morbidity and reduce the inpatient stay in emergency department. It should be recommended, once validated in a larger cohort, as the initial treatment of choice in the selected patients with food boneless bolus impaction in the emergency settings. Indeed, this management provides only minimal deviation from the current practice and is hence technically easy to learn and perform

Distal motor neuropathy associated with novel EMILIN1 mutation

Abstract Elastin microfibril interface-located proteins (EMILINs) are extracellular matrix glycoproteins implicated in elastogenesis and cell proliferation. Recently, a missense mutation in the EMILIN1 gene has been associated with autosomal dominant connective tissue disorder and motor-sensory neuropathy in a single family. We identified by whole exome sequencing a novel heterozygous EMILIN1 mutation c.748C>T [p.R250C] located in the coiled coil forming region of the protein, in four affected members of an autosomal dominant family presenting a distal motor neuropathy phenotype. In affected patient a sensory nerve biopsy showed slight and unspecific changes in the number and morphology of myelinated fibers. Immunofluorescence study of a motor nerve within a muscle biopsy documented the presence of EMILIN-1 in nerve structures. Skin section and skin derived fibroblasts displayed a reduced extracellular deposition of EMILIN-1 protein with a disorganized network of poorly ramified fibers in comparison with controls. Downregulation of emilin1a in zebrafish displayed developmental delay, locomotion defects, and abnormal axonal arborization from spinal cord motor neurons. The phenotype was complemented by wild-type zebrafish emilin1a, and partially the human wild-type EMILIN1 cRNA, but not by the cRNA harboring the novel c.748C>T [p.R250C]. These data suggest a role of EMILIN-1 in the pathogenesis of diseases affecting the peripheral nervous system