A theoretical approach for the electrochemical characterization of ciliary epithelium

The ciliary epithelium (CE) is the primary site of aqueous humor (AH) production, which results from the combined action of ultrafiltration and ionic secretion. Modulation of ionic secretion is a fundamental target for drug therapy in glaucoma, and therefore it is important to identify the main factors contributing to it. Since several ion transporters have been hypothesized as relevant players in CE physiology, we propose a theoretical approach to complement experimental methods in characterizing their role in the electrochemical and fluid-dynamical conditions of CE. As a first step, we compare two model configurations that differ by (i) types of transporters included for ion exchange across the epithelial membrane, and by (ii) presence or absence of the intracellular production of carbonic acid mediated by the carbonic anhydrase enzyme. The proposed model configurations do not include neurohumoral mechanisms such as P2Y receptor dependent, cAMP or calcium dependent pathways, which occur in the ciliary epithelium bilayer and influence the activity of ion transporters, pumps and channels present in the cell membrane. Results suggest that one of the two configurations predicts sodium and potassium intracellular concentrations and transmembrane potential much more accurately than the other. Because of its quantitative prediction power, the proposed theoretical approach may help relate phenomena at the cellular scale, that cannot be accessed clinically, with phenomena occuring at the scale of the whole eye, for which clinical assessment is feasible

Structure and Dynamics of RNA Guanine Quadruplexes in SARS-CoV-2 Genome. Original Strategies against Emerging Viruses

Guanine quadruplex (G4) structures in the viral genome have a key role in modulating viruses' biological activity. While several DNA G4 structures have been experimentally resolved, RNA G4s are definitely less explored. We report the first calculated G4 structure of the RG-1 RNA sequence of SARS-CoV-2 genome, obtained by using a multiscale approach combining quantum and classical molecular modeling and corroborated by the excellent agreement between the corresponding calculated and experimental circular dichroism spectra. We prove the stability of the RG-1 G4 arrangement as well as its interaction with G4 ligands potentially inhibiting viral protein translation

Architects of time: Labouring on digital futures

Drawing on critical analyses of the internet inspired by Gilles Deleuze and the Marxist autonomia movement, this paper suggests a way of understanding the impact of the internet and digital culture on identity and social forms through a consideration of the relationship between controls exercised through the internet, new subjectivities constituted through its use and new labour practices enabled by it. Following Castells, we can see that the distinction between user, consumer and producer is becoming blurred and free labour is being provided by users to corporations. The relationship between digital technologies and sense of community, through their relationship to the future, is considered for its dangers and potentials. It is proposed that the internet may be a useful tool for highlighting and enabling social connections if certain dangers can be traversed. Notably, current remedies for the lack of trust on the internet are questioned with an alternative, drawing on Zygmunt Bauman and Georg Simmel, proposed which is built on community through a vision of a ‘shared network’

Usefulness of Low-Dose Statin Plus Ezetimibe and/or Nutraceuticals in Patients With Coronary Artery Disease Intolerant to High-Dose Statin Treatment.

High-dose statin (HDS) therapy is recommended to reduce low-density lipoprotein cholesterol (LDL-C); however, some patients are unable to tolerate the associated side effects. Nutraceuticals have shown efficacy in lowering LDL-C. The aim of this study was to evaluate whether the combination of low-dose statin (LDS) plus ezetimibe (EZE) or LDS plus nutraceutical (Armolipid Plus [ALP] containing red yeast rice, policosanol, and berberine) can lead to a higher proportion of high-risk patients achieving target LDL-C. A secondary objective was to assess the efficacy of triple combination LDS + EZE + ALP in resistant patients (LDL-C >70 mg/dl). A randomized, prospective, parallel-group, single-blind study was conducted in patients with coronary artery disease (n = 100) who had undergone percutaneous coronary intervention in the preceding 12 months, were HDS-intolerant, and were not at LDL-C target (<70 mg/dl) with LDS alone. Patients received either LDS + EZE or LDS + ALP. Of the 100 patients, 33 patients (66%) treated with LDS + EZE and 31 patients (62%) treated with LDS + ALP achieved target LDL-C after 3 months, which was maintained at 6 months. Patients who did not achieve the therapeutic goal received a triple combination of LDS + EZE + ALP for a further 3 months. At 6 months, 28 of 36 patients (78%) achieved LDL-C target. Overall, 92% of patients enrolled in this study were at target LDL-C at 6 months. No patients in any group experienced major side effects. In conclusion, in HDS-intolerant coronary artery disease patients, the combination of LDS plus EZE and/or ALP represents a valuable therapeutic option allowing most patients to reach target LDL-C within 3 to 6 months

Characteristics of nursing homes and early preventive measures associated with risk of infection from COVID-19 in Lazio region, Italy: a retrospective case-control study

Objectives To understand which organisational-structural characteristics of nursing homes - also referred to as long-term care facilities (LTCFs) - and the preventative measures adopted in response to the pandemic are associated with the risk of a COVID-19 outbreak. Setting LTCFs in Lazio region in Italy. Design The study adopts a case-control design. Participants We included 141 facilities and 100 provided information for the study. Cases were defined as facilities reporting a COVID-19 outbreak (two or more cases) in March-December 2020; controls were defined as LTCFs reporting one case or zero. The exposures include the structural-organisational characteristics of the LTCFs as reported by the facilities, preventative measures employed and relevant external factors. Results Twenty facilities reported an outbreak of COVID-19. In binary logistic regression models, facilities with more than 15 beds were five times more likely to experience an outbreak than facilities with less than 15 beds OR=5.60 (CI 1.61 to 25.12; p value 0.002); admitting new residents to facilities was associated with a substantially higher risk of an outbreak: 6.46 (CI 1.58 to 27.58, p value 0.004). In a multivariable analysis, facility size was the only variable that was significantly associated with a COVID-19 outbreak OR= 5.37 (CI 1.58 to 22.8; p value 0.012) for larger facilities (&gt;15 beds) versus smaller (&lt;15 beds). Other characteristics and measures were not associated with an outbreak. Conclusion There was evidence of a higher risk of COVID-19 in larger facilities and when new patients were admitted during the pandemic. All other structural-organisational characteristics and preventative measures were not associated with an outbreak. This finding calls into question existing policies, especially where there is a risk of harm to residents. One such example is the restriction of visitor access to facilities, resulting in the social isolation of residents

Hypertension in adult Fabry&apos;s disease: is cardiotrophin-1 a diagnostic biomarker?

Background: Cardiotrophin-1 (CT-1), a cytokine produced by cardiomyocytes and non-cardiomyocytes in conditions of stress, can be used as a biomarker of left ventricular hypertrophy and dysfunction in hypertensive patients. Hypertension is one of the main adverse events in the third and last phase of Fabry's disease (FD). We measured CT-1 in order to examine its correlation with the vascular and cardiac alterations at different ages and assess its potential for use as a biomarker of hypertension in FD. Findings: The level of CT-1 was clearly higher in hypertensive adults than in adult FD patients. FD patients show a small, non-significant decrease in plasma CT-1 with age, while in hypertensive patients CT-1 in plasma rises strongly and highly significantly with age. Conclusions: CT-1 can be considered a good biomarker of the progression of hypertension with age, but particular care is needed when following hypertension in FD patients, since CT-1 does not correlate the same way with this disease

Up to 10.7-Gb/s high-PDG RSOA-based colorless transmitter for WDM networks

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Improving Male Partner Involvement in HIV-Positive Women's Care Through Behavioral Change Interventions in Malawi (WeMen Study): A Prospective, Controlled Before-and-After Study

Several strategies and interventions have been implemented to improve male partner involvement (MI) in Sub-Saharan Africa, but evidence on successful interventions is scarce. This controlled before-and-after intervention study aims to evaluate the impact of three interventions on male partners' involvement in HIV+ women's care in Malawi. We piloted these three interventions: the organization of a special day for men, the deployment of male champions in communities to increase awareness on MI, and the delivery of an incentive (food package) for couples attending the facility. We observed a significant increase in the number of women accompanied by their partners (from 48.5 to 81.4%) and the number of women feeling safe at home (from 63.5 to 95.2%) after the special day intervention. This outcome increased after the deployment of male champions in communities (from 44.0 to 75.0%). No significant improvement was observed in the site where we delivered the incentive to couples. Our findings showed that the special day for men and the use of male champions might effectively increase the male involvement in the health of their female partners