The psychosocial genomics paradigm of hypnosis and mind–body integrated psychotherapy: experimental evidence

The psychosocial genomics paradigm first proposed by Ernest Rossi established an epistemological shift in our application of hypnosis. We present original experimental research conducted within this paradigm that highlights the mind–gene relationship and, in particular, the positive health effects associated with hypnosis and mind–body integrated psychotherapy. We document that these approaches can stimulate epigenetic modifications and the expression of genes related to anti-inflammatory processes. These strategies strengthen the immune system and reduce oxidative stress both in normal and in oncological participants

Small steps towards the potential of ‘preventive’ treatment of early phosphate loading in chronic kidney disease patients

Few clinical studies have investigated the value of phosphate (P)-lowering therapies in early chronic kidney disease (CKD) patients in whom hyperphosphataemia has not yet clearly developed and they report conflicting and even unexpected results. In this issue of Clinical Kidney Journal, de Krijger et al. found that sevelamer carbonate (4.8 g/day for 8 weeks) did not induce a significant reduction of pulse wave velocity (PWV) and that fibroblast growth factor 23 (FGF23) did not decrease despite a decline in 24-h urine P excretion. To some extent these findings challenge the concept that 'preventive' P binder therapy to lower FGF23 is a useful approach, at least over this short period of time. Interestingly, in a subgroup of patients with absent or limited abdominal vascular calcification, treatment did result in a statistically significant reduction in adjusted PWV, suggesting that PWV is amenable to improvement in this subset. Interpretation of the scarce and heterogeneous observations described in early CKD remains difficult and causality and/or the possibility of 'preventive' treatment may not yet be completely disregarded. Moreover, de Krijger et al. contribute to the identification of new sources of bias and methodological issues that may lead to more personalized treatments, always bearing in mind that not all patients and not all P binders are equal

GIS mapping of the archaeological sites in the Molise region (Italy)

The Molise Region, on the Adriatic coast of southern Italy, experienced human presence since prehistoric times. Site distribution is not homogeneous throughout the region and a comprehensive census of all known archaeological sites has never been performed. In this paper, we present the results of a three-year project for the GIS mapping and database creation for all the known archaeological sites of the Molise Region. As a result, 3111 archaeological sites have been mapped, stored in a GIS database and then analysed through Spatial Analyst tools. Most of the mapped sites have been classified as area of archaeological finds (57.1% of the total sites), followed by settlements (12.9%) and buildings (9.8%). Site distribution is mainly clustered along the Biferno river valley, in the central and in the south-western sectors of the Molise Region. The largest human occupation of the region occurred during the Samnite and Roman ages. Archaeological sites are also located at different elevation a.s.l., with a general increasing trend of site elevation through time. This GIS database is, up to now, the most complete census of archaeological sites in the study area, thus representing a powerful tool to promote the archaeological heritage of the Molise Region and to address urban planning

Phytotoxicity to and uptake of flumequine used in intensive aquaculture on the aquatic weed, Lythrum salicaria L.

Phytotoxicity of Flumequine on the aquatic weed Lythrum salicaria L. was determined by two laboratory models: a single concentration test, by which the effects of 100 mg l(-1) were evaluated after 10, 20, 30 days and a multiple concentration test, by which the effects of 5000-1000-500-100-50 mu g l(-1) were evaluated after 35-day exposure. 100 mg l(-1) are highly toxic and significantly decrease the growth of plants; this effect increases with time. Concentrations between 5000 and 50 mu g l(-1) induced hormesis in plants, by significantly increasing mean number and dimension of leaves and secondary roots. The effect is the highest at 50 mu g l(-1) and decreases with increase in concentration. Both toxic effect and hormesis can be related to plant drug uptake, quite high, in the order of mu g g(-1). The ecological implication of Flumequine contamination in aquatic environments and the possible use of Lythrum salicaria for bioremediation and/ or monitoring technique are discussed. (C) 2000 Elsevier Science Ltd. All rights reserved

Rationale for Medium Cutoff Membranes in COVID-19 Patients Requiring Renal Replacement Therapy

The current pandemic of coronavirus disease 2019 (COVID-19) spotlighted the vulnerability of patients with chronic kidney disease stage 5 on maintenance hemodialysis (HD) to the viral infection. Social distancing is the most effective preventive measure to reduce the risk of infection. Nonetheless, the necessity to frequently reach the dialysis center and the inherent social gathering both impede social distancing and also self-quarantine for infected individuals. A baseline hyperinflammatory state driven by factors such as the retention of uremic toxins afflicts these patients. Concomitantly, a condition of relative immunosuppression is also attributed to similar factors. The use of high-flux (HF) dialyzers for HD is the standard of care. However, with HF membranes, the removal of large middle molecules is scant. Medium cutoff (MCO) dialyzers are a new class of membranes that allow substantial removal of large middle molecules with negligible albumin losses. Recent trials confirmed long-term safety and long-term sustained reduction in the concentration of large uremic toxins with MCO dialyzers. Herein, we discuss the rationale for applying MCO membranes in COVID-19 patients and its possible immunoadjuvant effects that could mitigate the burden of COVID-19 infection in dialysis patients. We also discuss the direct cytopathic effect of the virus on renal tissue and extracorporeal blood purification techniques that can prevent kidney damage or reduce acute kidney injury progression

The intriguing case of motor neuron disease: ALS and SMA come closer

MNDs (motor neuron diseases) form a heterogeneous group of pathologies characterized by the progressive degeneration of motor neurons. More and more genetic factors associated with MND encode proteins that have a function in RNA metabolism, suggesting that disturbed RNA metabolism could be a common underlying problem in several, perhaps all, forms of MND. In the present paper we review recent developments showing a functional link between SMN (survival of motor neuron), the causative factor of SMA (spinal muscular atrophy), and FUS (fused in sarcoma), a genetic factor in ALS (amyotrophic lateral sclerosis). SMN is long known to have a crucial role in the biogenesis and localization of the spliceosomal snRNPs (small nuclear ribonucleoproteins), which are essential assembly modules of the splicing machinery. Now we know that FUS interacts with SMN and pathogenic FUS mutations have a significant effect on snRNP localization. Together with other recently published evidence, this finding potentially links ALS pathogenesis to disturbances in the splicing machinery, and implies that pre-mRNA splicing may be the common weak point in MND, although other steps in mRNA metabolism could also play a role. Certainly, further comparison of the RNA metabolism in different MND will greatly help our understanding of the molecular causes of these devastating diseases

Multistep, sequential control of the trafficking and function of the multiple sulfatase deficiency gene product, SUMF1 by PDI, ERGIC-53 and ERp44.

Sulfatase modifying factor 1 (SUMF1) encodes for the formylglicine generating enzyme, which activates sulfatases by modifying a key cysteine residue within their catalytic domains. SUMF1 is mutated in patients affected by multiple sulfatase deficiency, a rare recessive disorder in which all sulfatase activities are impaired. Despite the absence of canonical retention/retrieval signals, SUMF1 is largely retained in the endoplasmic reticulum (ER), where it exerts its enzymatic activity on nascent sulfatases. Part of SUMF1 is secreted and paracrinally taken up by distant cells. Here we show that SUMF1 interacts with protein disulfide isomerase (PDI) and ERp44, two thioredoxin family members residing in the early secretory pathway, and with ERGIC-53, a lectin that shuttles between the ER and the Golgi. Functional assays reveal that these interactions are crucial for controlling SUMF1 traffic and function. PDI couples SUMF1 retention and activation in the ER. ERGIC-53 and ERp44 act downstream, favoring SUMF1 export from and retrieval to the ER, respectively. Silencing ERGIC-53 causes proteasomal degradation of SUMF1, while down-regulating ERp44 promotes its secretion. When over-expressed, each of three interactors favors intracellular accumulation. Our results reveal a multistep control of SUMF1 trafficking, with sequential interactions dynamically determining ER localization, activity and secretion