Purity and impurity in nondualistic Śaiva Tantrism

Indian civilisation has been strongly characterised by the work of containment erected by the Brahmanical elite over the almost two thousand years of its grandiose attempt at culturally and so- cially dominating the Indian world as a whole. Lacking any direct power, the Brahmans have re- placed it by successfully imposing, as an alternative, an opposition between purity and impurity that has marked every aspect of Indian culture: purity of spirit, purity of philosophy, purity of rites, purity of language, purity of social and religious conduct, etc. Nondualistic Śaiva Tantrism’s re- sponse starts by questioning the legitimacy and very basis of the division between pure and impure, destined to crumble progressively beneath the thrust of deliberate “non-dual” behaviour (advaitācāra). Purity or impurity are not properties of things. They are quali cations pertaining to the knower depending on whether he perceives the object as united with consciousness or not. “Impure is what has fallen away from consciousness: therefore everything is pure if it has achieved identity with consciousness.” Moreover, if Śiva “is” the universe, there may be no impu- rity. In the Tantric texts special emphasis is laid on the necessity to overcome śaṅkā (“hesitation, inhibition”), viewed as the ultimate purpose of the Brahmanical rules concerning purity/impurity, acting as a subtle and effective instrumentum regni

Metformin therapy effects on the expression of sodium-glucose cotransporter 2, leptin, and sirt6 levels in pericoronary fat excised from pre-diabetic patients with acute myocardial infarction

Background and purpose: pericoronary fat over-inflammation might lead to the development and destabilization of coronary plaque in patients with pre-diabetes (PDM). Notably, pericoronary fat could over-express the sodium-glucose cotransporter 2 (SGLT2) and leptin, along with decreased sirtuin 6 (SIRT6) expression in PDM vs. normoglycemic (NG) patients undergoing coronary artery bypass grafting (CABG) for acute myocardial infarction (AMI). However, in the current study, we evaluated inflammatory markers, SGLT2, SIRT6, and leptin levels in pericoronary fat and, subsequently, 12-month prognosis comparing PDM to NG subjected to CABG for AMI. In addition, we evaluated in PDM patients the effects of metformin therapy on SIRT6 expression, leptin, and SGLT2 levels, and assessed its beneficial effect on nitrotyrosine and inflammatory cytokine levels. Methods: we studied AMI patients referred for CABG, divided into PDM and NG-patients. PDM patients were divided into never-metformin users and metformin users. Finally, we evaluated major adverse cardiac events (MACE) at a 12-month follow-up. Results: the MACE was 9.1% in all PDM and 3% in NG patients (p < 0.05). Metformin users presented a significantly lower MACE rate in PDM than never-metformin users (p < 0.05). PDM showed higher inflammatory cytokines, 3-nitrotyrosine levels, SGLT2, and leptin content, and decreased SIRT6 protein levels in pericoronary fat compared to NG-patients (p < 0.05). PDM never-metformin-users showed higher SGLT2 and leptin levels in pericoronary fat than current-metformin-users (p < 0.05). Conclusions: metformin therapy might ameliorate cardiovascular outcomes by reducing inflammatory parameters, SGLT2, and leptin levels, and finally improving SIRT6 levels in AMI-PDM patients treated with CABG

Efficacy and durability of multifactorial intervention on mortality and MACEs:a randomized clinical trial in type-2 diabetic kidney disease

Background: Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods: Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure 40/50 mg/dL for men/women and < 175 mg/dL, respectively). Primary endpoint was MACEs occurrence by end of follow-up phase. Secondary endpoints included single components of primary endpoint and all-cause death. Results: At the end of intervention period (median 3.84 and 3.40 years in MT and SoC group, respectively), targets achievement was significantly higher in MT. During 13.0 years (IQR 12.4–13.3) of follow-up, 262 MACEs were recorded (116 in MT vs. 146 in SoC). The adjusted Cox shared-frailty model demonstrated 53% lower risk of MACEs in MT arm (adjusted HR 0.47, 95%CI 0.30–0.74, P = 0.001). Similarly, all-cause death risk was 47% lower (adjusted HR 0.53, 95%CI 0.29–0.93, P = 0.027). Conclusion: MT induces a remarkable benefit on the risk of MACEs and mortality in high-risk DKD patients. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT0053592

Solving patients with rare diseases through programmatic reanalysis of genome-phenome data.

Funder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health); doi: https://doi.org/10.13039/100011272; Grant(s): 305444, 305444Funder: Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness); doi: https://doi.org/10.13039/501100003329Funder: Generalitat de Catalunya (Government of Catalonia); doi: https://doi.org/10.13039/501100002809Funder: EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj); doi: https://doi.org/10.13039/501100008530Funder: Instituto Nacional de Bioinformática ELIXIR Implementation Studies Centro de Excelencia Severo OchoaFunder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health)Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP's Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics

Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases.

For the first time in Europe hundreds of rare disease (RD) experts team up to actively share and jointly analyse existing patient's data. Solve-RD is a Horizon 2020-supported EU flagship project bringing together >300 clinicians, scientists, and patient representatives of 51 sites from 15 countries. Solve-RD is built upon a core group of four European Reference Networks (ERNs; ERN-ITHACA, ERN-RND, ERN-Euro NMD, ERN-GENTURIS) which annually see more than 270,000 RD patients with respective pathologies. The main ambition is to solve unsolved rare diseases for which a molecular cause is not yet known. This is achieved through an innovative clinical research environment that introduces novel ways to organise expertise and data. Two major approaches are being pursued (i) massive data re-analysis of >19,000 unsolved rare disease patients and (ii) novel combined -omics approaches. The minimum requirement to be eligible for the analysis activities is an inconclusive exome that can be shared with controlled access. The first preliminary data re-analysis has already diagnosed 255 cases form 8393 exomes/genome datasets. This unprecedented degree of collaboration focused on sharing of data and expertise shall identify many new disease genes and enable diagnosis of many so far undiagnosed patients from all over Europe

Solving unsolved rare neurological diseases-a Solve-RD viewpoint.

Funder: Durch Princess Beatrix Muscle Fund Durch Speeren voor Spieren Muscle FundFunder: University of Tübingen Medical Faculty PATE programFunder: European Reference Network for Rare Neurological Diseases | 739510Funder: European Joint Program on Rare Diseases (EJP-RD COFUND-EJP) | 44140962

Observations on yogipratyaksa

From a relatively marginal theme in the cursus of the yoga adepts, the issue of yogipratyaksa – the special power of perception that most of the Indian traditions attribute to the yogis – opens to a far wider dimension, absolutely crucial for Indian philosophy as a whole: the question of whether a seeker of truth may do without revealed tradition. In addressing the issue of yogipratyaksa, the Buddhists are driven by two different yet concentric aims: on the one hand, to admit in the individual the capacity of seeking for truth by his forces alone, independently from the support of any revelation, and, on the other, to protect the central tenets of Buddhism from brahmanical critics, who through sophisticated dialectics are capable of questioning any truth obtained by way of mere reasoning

Atti del Convegno "Passioni ed emozioni in India e in Tibet", Roma Sapienza, 27 gennaio 2007. In: RIVISTA DEGLI STUDI ORIENTALI, vol. 80

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