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Repeat expansion disorders (REDs) are a devastating group of predominantly neurological diseases. Together they are common, affecting 1 in 3,000 people worldwide with population-specific differences. However, prevalence estimates of REDs are hampered by heterogeneous clinical presentation, variable geographic distributions and technological limitations leading to underascertainment. Here, leveraging whole-genome sequencing data from 82,176 individuals from different populations, we found an overall disease allele frequency of REDs of 1 in 283 individuals. Modeling disease prevalence using genetic data, age at onset and survival, we show that the expected number of people with REDs would be two to three times higher than currently reported figures, indicating underdiagnosis and/or incomplete penetrance. While some REDs are population specific, for example, Huntington disease-like 2 in Africans, most REDs are represented in all broad genetic ancestries (that is, Europeans, Africans, Americans, East Asians and South Asians), challenging the notion that some REDs are found only in specific populations. These results have worldwide implications for local and global health communities in the diagnosis and counseling of REDs.

CSCs are a small population of poorly differentiated cancer cells that have superior tumor-repopulating potential and (at least in some cancers) drive disease progression and resistance to therapy.Similarly to their normal counterparts, CSCs harness a variety of mechanisms to evade immune recognition and elimination.Cancer cell stemness is maintained by multiple DNA and histone epigenetic alterations that also enable immunoevasion.Targeting epigenetic alterations that promote CSC stemness and immunoevasion stands out as a promising approach to increase the sensitivity of some tumors to immunotherapy.

Background:Gastroesophageal reflux disease (GERD), the most common esophageal disorder worldwide, is a progressive condition that may lead to Barrett’s esophagus and adenocarcinoma. Upfront therapy with proton pump inhibitors is ineffective in up to 40% of patients. The scope of surgical therapy is to reconstruct the natural antireflux barrier provided by the diaphragmatic crura, the lower esophageal sphincter, and the gastroesophageal flap valve. Summary:For 70 years, the 360° Nissen fundoplication has dominated the surgical scenario and is still considered the gold-standard treatment. However, over the past two decades, the Toupet and Dor partial fundoplications have emerged as alternative options to decrease the incidence of dysphagia and gas-bloat syndrome. Randomized and observational clinical studies have shown that the outcomes of partial fundoplication compare favorably with those of the Nissen and can provide satisfactory quality of life minimizing the risk of side effects. However, reflux control and anatomical integrity of partial fundoplications may fade away over time. Further research and close scrutiny of new surgical procedures and technologies is in progress to improve clinical outcomes and provide a more personalized and durable antireflux therapy. Key Messages:Laparoscopic antireflux surgery is a safe and effective therapy for GERD. It should be performed in centers offering a comprehensive diagnostic pathway and a spectrum of techniques tailored to the individual GERD phenotype. Fundoplication is a surgical procedure to correct both hiatus hernia and gastroesophageal reflux disease. These conditions cause symptoms (acid reflux, heartburn, and regurgitation) and complications (chronic inflammation possibly leading to cancer). The fundoplication consists of encircling the distal part of the esophagus (food pipe) with a portion of the upper portion of the stomach to allow normal passage of food while preventing the return of food to the esophagus and the mouth. Over the past 70 years, the advantages and drawbacks of this operation have been widely reported. Still, the vast majority of patients and physicians have not fully embraced this therapeutic modality due to the fear of side effects such as difficult swallowing and bloating. Therefore, a partial fundoplication approach has been proposed to avoid these side effects and to provide a surgical repair that does not alter quality of life while maintaining the patient free from reflux and not dependent on drugs (proton pump inhibitors). However, partial fundoplications may not tighten enough the sphincter (valve) located between the esophagus and the stomach, and may not be durable over time. This paper describes the history of fundoplication, the mechanisms by which gastroesophageal reflux causes symptoms and complications, the indication for surgery, the main steps of laparoscopic (keyhole) surgery, and the search for innovative and minimally invasive techniques to strengthen the sphincter in order to cure symptoms and protect the esophagus from the deleterious effects of acid reflux.

pH-sensitive peptides bind and traverse lipid membranes in response to changes in pH. They can be used to target tumors and other acidic tissues. We investigate the influence of acidic lipids on the pH-driven adsorption of recently synthesized peptides. Using a statistical-thermodynamic theory that takes into account the acid–base chemistry of peptides and lipids, we find that the presence of acidic lipids amplifies changes in peptide surface concentration when transitioning from high to low pH. We study cyclic and linear peptides, containing tryptophan, glutamic acid, and arginine residues, examining their behavior in both neutral and acidic membranes. Membrane binding consistently results from the shallow insertion of tryptophan residues with hydrophilic residues facing the aqueous solution. Regardless of the pH, the peptide’s geometry predominantly determines the orientation and distribution of residues. Notably, we find that not only the extent of adsorption is pH-sensitive but also the underlying adsorption mechanism: it is barrier-free at low pH but hindered by a large free energy barrier at high pH. Hence, under more acidic conditions, pH-sensitive peptides show facilitated adsorption both kinetically and thermodynamically.

Binder Jetting (BJT) is a non-fusion-based Additive Manufacturing (AM) technique. It consists of the selective deposition of a liquid binder to join powder particles, thereby enabling the creation of near-net-shaped parts.

ABSTRACTIntroductionCardiovascular disease (CVD) is one of the global leading causes of morbidity and mortality in chronic kidney disease (CKD) patients. Vascular calcification (VC) is a major cause of CVD in this population and is the consequence of complex interactions between inhibitor and promoter factors leading to pathological deposition of calcium and phosphate in soft tissues. Different pathological landscapes are associated with the development of VC, such as endothelial dysfunction, oxidative stress, chronic inflammation, loss of mineralization inhibitors, release of calcifying extracellular vesicles (cEVs) and circulating calcifying cells.Areas coveredIn this review, we examined the literature and summarized the pathophysiology, biomarkers and focused on the treatments of VC.Expert opinionEven though there is no consensus regarding specific treatment options, we provide the currently available treatment strategies that focus on phosphate balance, correction of vitamin D and vitamin K deficiencies, avoidance of both extremes of bone turnover, normalizing calcium levels and reduction of inflammatory response and the potential and promising therapeutic approaches liketargeting cellular mechanisms of calcification (e.g. SNF472, TNAP inhibitors).Creating novel scores to detect in advance VC and implementing targeted therapies is crucial to treat them and improve the future management of these patients.

Deformable linear objects (DLOs), such as cables, wires, ropes, and elastic tubes, are numerously present both in domestic and industrial environments. Unfortunately, robotic systems handling DLOs are rare and have limited capabilities due to the challenging nature of perceiving them. Hence, we propose a novel approach named RT-DLO for real-time instance segmentation of DLOs. First, the DLOs are semantically segmented from the background. Afterward, a novel method to separate the DLO instances is applied. It employs the generation of a graph representation of the scene given the semantic mask where the graph nodes are sampled from the DLOs center-lines whereas the graph edges are selected based on topological reasoning. RT-DLO is experimentally evaluated against both DLO-specific and general-purpose instance segmentation deep learning approaches, achieving overall better performances in terms of accuracy and inference time.

Graphical Abstract

Focal radiation therapy (RT) has been successfully employed to clinically manage multiple types of cancer for more than a century. Besides being preferentially cytotoxic for malignant cells over their nontransformed counterparts, RT elicits numerous microenvironmental alterations that appear to factor into its therapeutic efficacy. Here, we briefly discuss immunostimulatory and immunosuppressive microenvironmental changes elicited by RT and their impact on tumor recognition by the host immune system.

The pediatric oncology unit at the Rajiv Gandhi Cancer Institute and Research Center (RGCI & RC), a nonprofit medical facility and research institute based in Delhi, India, sought to improve clinical nursing practice through nurse leadership training supported by international nursing mentorship. A nursing team leadership program with a goal to strengthen practice was designed in collaboration with the RGCI & RC nurse education department and pediatric oncology physicians on the unit. Two expert oncology nurses from the United States made multiple visits from 2017 to 2019 to support the development of the leadership program and the resulting practice changes. Specific areas of nursing addressed through these efforts included attention to education, practice, and leadership. Selected processes were improved by the following: (a) development of a pediatric oncology nursing orientation program to follow general onboarding by the nursing education department, (b) strengthening and updating standard operating procedures for nursing, and (c) development of a nursing Team Leads program. Four team leads completed training, and staff nurses are now active members in the care of patients and opining themselves when decision-making occurs during rounds. RGCI & RC nurses have written abstracts and posters accepted at national and international conferences, which further strengthens their profile in the larger pediatric oncology professional community.

iNKT cells account for a relevant fraction of effector T-cells in the intestine and are considered an attractive platform for cancer immunotherapy. Although iNKT cells are cytotoxic lymphocytes, their functional role in colorectal cancer (CRC) is still controversial, limiting their therapeutic use. Thus, we examined the immune cell composition and iNKT cell phenotype of CRC lesions in patients (n = 118) and different murine models. High-dimensional single-cell flow-cytometry, metagenomics, and RNA sequencing experiments revealed that iNKT cells are enriched in tumor lesions. The tumor-associated pathobiont Fusobacterium nucleatuminduces IL-17 and Granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in iNKT cells without affecting their cytotoxic capability but promoting iNKT-mediated recruitment of neutrophils with polymorphonuclear myeloid-derived suppressor cells-like phenotype and functions. The lack of iNKT cells reduced the tumor burden and recruitment of immune suppressive neutrophils. iNKT cells in-vivoactivation with α-galactosylceramide restored their anti-tumor function, suggesting that iNKT cells can be modulated to overcome CRC-associated immune evasion. Tumor co-infiltration by iNKT cells and neutrophils correlates with negative clinical outcomes, highlighting the importance of iNKT cells in the pathophysiology of CRC. Our results reveal a functional plasticity of iNKT cells in CRC, suggesting a pivotal role of iNKT cells in shaping the tumor microenvironment, with relevant implications for treatment.

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This paper presents the ECCANDE project, one of the first Special Protection Schemes (SPS) conceived to rely on the structure of a Wide-Area Monitoring, Protection, and Control System (WAMPACS) and currently operating in a real, large-sized power system. This project was developed and implemented to enable the interconnection between the Argentinean and Paraguayan bulk power transmission systems, which involves and directly affects two of the largest hydropower plants in the world (the Itaipu and Yacyreta power plants). Building this WAMPACS-based SPS took more than a decade of work performed by multiple teams, involving modeling, planning studies, design, manufacturing, real-time hardware-in-the-loop (HIL) simulation for equipment testing, implementation, commissioning, field tests and evaluation of daily operation. The paper describes how system stability problems (detected during the initial studies for the interconnection) made it clear that the ECCANDE SPS had to be a WAMPACS-based one, and how its architecture and logic functions were conceived to deal with these problems. The results of HIL real-time simulations and a main field test show that the ECCANDE SPS enabled the interconnection, successfully protecting against the loss of synchronism between the Itaipu and Yacyreta power plants before the system separation.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease.

Scenarios are extensively used throughout the safety validation and verification of automated vehicles, therefore creating a list of scenarios as a common reference for the manufacturers and Type Approval Authorities is needed to ensure an even-handed type approval process. The present paper offers solutions for this need, addressing issues related to the establishment, population and update principles of a common scenario database. It describes the positioning of this database in the verification framework of automated vehicles and presents the different scenario types implied. Going deeper in the details, the possible layers needed for the definition of a scenario are also presented. Finally, the paper introduces the first steps made on the definition of a scenarios catalogue for the validation of L3 highway applications, established at UNECE level, and for L4 applications, established at EU level.

Automated Vehicles (AVs) safety and security bring significant concerns for introducing this new technology on public roads, requiring an adequate response from regulators. Several international working groups were established in the last years at both European Union (EU) and United Nations (UN) levels to work out a multi-pillar approach, encompassing all track and public road testing for safety verification. This paper focuses on track testing as part of a harmonized testing procedure to establish a type approval framework for AVs with complementary parts. Building on the experience of UNR157, the first international regulation to cover Level 3 AVs, the manuscript presents a forward-looking approach addressing critical safety aspects that can be verified on a track, including scenario difficulty categorization and the analysis of AVs behavior in case of collisions.

In June 2020 the United Nations World Forum for Harmonization of Vehicle Regulations adopted the first global Regulation for the approval of automated driving vehicles. Although this first Regulation represents a very important milestone for the automotive sector, it covers a very specific use-case, namely conditional automated driving (level 3) for motorway applications. Transport technology is evolving at an unprecedented pace towards higher levels of automation and its safe deployment requires a more comprehensive regulatory framework, also addressing other operating environments. This paper presents an overview of the European Union approach for safety approval of automated vehicles beyond level 3 highway applications.

A new EU regulation is being drafted to lay down the technical specifications concerning type-approval of Automated Driving System (ADSs). One of the requirements included in the regulation concerns the conditions for merging or crossing unsignalized intersections in the presence of oncoming privileged traffic. The requirements have been derived by studying the gap that human drivers usually accept in the same case. In particular, it has been found that a minimum separation in terms of Time to Collision (TTC) is required for the whole manoeuvre and it is demonstrated that only a percentage of the most aggressive drivers accept gaps that are smaller than what is required by the regulation.

We explore the use of residual networks and neural attention for multiple argument mining tasks. We propose a residual architecture that exploits attention, multi-task learning, and makes use of ensemble, without any assumption on document or argument structure. We present an extensive experimental evaluation on five different corpora of user-generated comments, scientific publications, and persuasive essays. Our results show that our approach is a strong competitor against state-of-the-art architectures with a higher computational footprint or corpus-specific design, representing an interesting compromise between generality, performance accuracy and reduced model size.

AbstractThe high reliance of the European livestock sector on imported soybean meal (SBM), especially from South America, poses environmental problems, like greenhouse gas emissions for transportation and land-use change with the loss of carbon stock and biodiversity. Aim of the present study was to evaluate the partial substitution of SBM with whole-plant soybean silage in the diet of dairy cows. Thirty-six lactating Holstein cows were arranged according to a change-over design, with 2 weeks of adaptation and 5 days of sampling per period. A control diet (CON) was based on maize silage and SBM, representing 10.7% of total dry matter (DM). In a soybean silage diet (SBS) 35% (on DM basis) of SBM was replaced by soybean silage. The dietary treatment did not affect DM intake, milk production, and dairy efficiency while cows fed SBS resulted in lower milk crude protein (3.43 vs. 3.55%, p < .001) and higher milk urea (30.5 vs. 28.7 mg/dL, p = .002), in comparison with CON. Nutrients digestibility was lower for SBS than CON; particularly fibre digestibility was 31.5 vs. 38.8% (p < .001). The efficiency of nitrogen utilisation was higher for CON than SBS (32.7 vs. 31.3%, p = .003). Soybean silage did not penalise feed intake and milk production. However, to fully exploit this forage, digestibility, and nitrogen utilisation efficiency should be improved.HighlightsSoybean silage can substitute one-third of soybean meal in dairy cow dietSoybean silage inclusion in the diet did not affect milk yield and DMISoybean silage inclusion in the diet reduced N use efficiency

Background: The early detection of neurocognitive disorders, especially when mild, is a key issue of health care systems including the Italian Dementia National Plan. The Mini-Mental State Examination (MMSE), i.e., the reference screening tool for dementia in Italian Memory Clinics, has low sensitivity in detecting mild cognitive impairment (MCI) or mild dementia.Objective: Availability of a 10-minute screening test sensitive to MCI and mild dementia, such as the Montreal Cognitive Assessment (MoCA), is relevant in the field. This study presents initial validity and reliability data for the Italian version of MoCA 7.1 that is being collected as part of a large ongoing longitudinal study to evaluate the rate of incident MCI and dementia in older adults.Methods: MoCA 7.1 and MMSE were administered to cognitive impaired patients (n?=?469; 214 with MCI, 255 with dementia; mean age: 75.5; 52% females,) and healthy older adults (n?=?123, mean age: 69.7, 64 % females).Results: Test-retest (0.945, p?

Cancer stem cells (CSCs) are a subpopulation of cancer cells endowed with high tumorigenic, chemoresistant and metastatic potential. Nongenetic mechanisms of acquired resistance are increasingly being discovered, but molecular insights into the evolutionary process of CSCs are limited. Here, we show that type I interferons (IFNs-I) function as molecular hubs of resistance during immunogenic chemotherapy, triggering the epigenetic regulator demethylase 1B (KDM1B) to promote an adaptive, yet reversible, transcriptional rewiring of cancer cells towards stemness and immune escape. Accordingly, KDM1B inhibition prevents the appearance of IFN-I-induced CSCs, both in vitro and in vivo. Notably, IFN-I-induced CSCs are heterogeneous in terms of multidrug resistance, plasticity, invasiveness and immunogenicity. Moreover, in breast cancer (BC) patients receiving anthracycline-based chemotherapy, KDM1B positively correlated with CSC signatures. Our study identifies an IFN-I → KDM1B axis as a potent engine of cancer cell reprogramming, supporting KDM1B targeting as an attractive adjunctive to immunogenic drugs to prevent CSC expansion and increase the long-term benefit of therapy.

OBJECTIVE--It is still controversial whether sirolimus-eluting stem (SES) and paclitaxel-eluting stent (PES) are equally effective in patients with diabetes. In these patients, multiple individual variables may be responsible for neointimal [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2006.02.031 Byline: Andrea Galassi (a), Kristi Reynolds (a), Jiang He (a)(b) Keywords: Metabolic syndrome; Meta-analysis; Cardiovascular disease Abstract: The use of different definitions of the metabolic syndrome has led to inconsistent results on the association between the metabolic syndrome and risk of cardiovascular disease. We examined the association between the metabolic syndrome and risk of cardiovascular disease. Author Affiliation: (a) Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, La (b) Department of Medicine, Tulane University School of Medicine, New Orleans, La. Article Note: (footnote) Supported in part by grant number K12HD43451 from the National Institutes of Health to Dr. Reynolds.

•a new facial approximation is offered of the famous mummy of Minirdis, an ancient Egyptian male adolescent dated about 2,300years ago.•the importance of image acquisition and analysis from videos of radiological content is stressed and a methodology for its implementation is detailed.•the mummy's endocast is analysed and its large dimensions discussed.

Human head lice Pediculus humanus capitisDe Geer (Phthiraptera: Pediculidae) are ectoparasites that cause pediculosis, a global scale disease mainly found in school-age children. Previous works from our laboratory found nonanal, sulcatone, and geranylacetone as the main human scalp volatile components, and individually evaluated their attraction to head lice using an olfactometer. In this work, we compared how their blends at different concentrations attract head lice, and how their blended effect compares to the effect of isolated compounds. At the concentrations evaluated, individual components did not show attraction towards head lice, but a ternary mixture of them was attractive. Moreover, a solvent extract from the human head scalp was analyzed by GC-MS, finding that tetradecanoic acid, palmitic acid, oleic acid, palmitoleic acid, and squalene are the most abundant components. Attraction to these individual compounds at natural concentrations was tested by bioassays in a circular experimental arena. No attraction was observed when the components were tested individually, but when they were evaluated as a blend they attracted head lice. This work presents new information about how chemical signals are attractive at certain concentrations and proportions. This information could be used to better understand communication mechanisms in head lice and for the development of louse repellents.

Dying mammalian cells emit numerous signals that interact with the host to dictate the immunological correlates of cellular stress and death. In the absence of reactive antigenic determinants (which is generally the case for healthy cells), such signals may drive inflammation but cannot engage adaptive immunity. Conversely, when cells exhibit sufficient antigenicity, as in the case of infected or malignant cells, their death can culminate with adaptive immune responses that are executed by cytotoxic T lymphocytes and elicit immunological memory. Suggesting a key role for immunogenic cell death (ICD) in immunosurveillance, both pathogens and cancer cells evolved strategies to prevent the recognition of cell death as immunogenic. Intriguingly, normal cells succumbing to conditions that promote the formation of post-translational neoantigens (for example, oxidative stress) can also drive at least some degree of antigen-specific immunity, pointing to a novel implication of ICD in the etiology of non-infectious, non-malignant disorders linked to autoreactivity.

Coinage metal cyclic trinuclear compounds (CTCs) are an emerging class of metal coordination compounds that are valuable for many fine optoelectronic applications, even though the reactivity dependence by the different bridging ligands remains somewhat unclear. In this work, to furnish some hints to unravel the effect of substituents on the chemistry of Au(I) CTCs made of a specific class of bridging ligand, we have considered two imidazolate Au(I) CTCs and the effect of different substituents on the pyrrolic N atoms relative to classic metal oxidations with I2or by probing electrophilic additions. Experimental suggestions depict a thin borderline between the addition of MeI to the N-methyl or N-benzyl imidazolyl CTCs, which afford the oxidized CTC in the former and the ring opening of the CTC and the formation of carbene species in the latter. Moreover, the reactions with iodine yield to the oxidation of the metal centers for the former and just of a metal center in the latter, even in molar excess of iodine. The analysis of the bond distances in the X-ray crystal structures of the oxidized highlights that Au(III)-C and Au(III)-N bonds are longer than observed for Au(I)–C and Au(I)–N bonds, as formally not expected for Au(III) centers. Computational studies converge on the attribution of these discrepancies to an additional case of inverted ligand field (ILF), which solves the question with a new interpretation of the Au(I)–ligand bonding in the oxidized CTCs, which furnishes a new interpretation of the Au(I)-ligand bonding in the oxidized CTCs, opening a discussion about addition/oxidation reactions. Finally, the theoretical studies outputs depict energy profiles that are compatible with the experimental results obtained in the reaction of the two CTCs toward the addition of I2, MeI, and HCl.

The adoption of computerised adaptive testing (CAT) instead of classical testing (FIT) raises questions from both teachers' and students' perspectives. The scientific literature shows that teachers using CAT instead of FIT should experience shorter times to complete the assessment and obtain more precise evaluations. As for the students, adaptive testing seems to increase their engagement, whereas the impossibility to revise the already given questions is usually seen as a detrimental characteristic. In such a context, the paper reports on a study concerning the aforementioned points. The outcomes seem almost all inline with the literature: no particular usability issues were detected, CAT is faster than FIT, and CAT does not seem more engaging than FIT. All these findings are reported in the conclusions as a list of suggestions to teachers interested in switching from FIT to CAT.

Modern applications related to service or production can nowadays benefit from the introduction of collaborative robots already available on the market and endowed with several advanced features such as precise torque control or safe physical interaction with operators. More importantly, collaborative robots allow operators to teach end-effector trajectories by means of physical interaction – known as kinesthetic teaching – which is one of the most intuitive programming-by-demonstration techniques. However, important functionalities provided by modern collaborative robots, like the possibility of performing smooth interactions, cannot be programmed intuitively with the available framework of kinesthetic teaching. In the present study, we propose and experimentally evaluate a robot programming framework for the simultaneous teaching of both trajectories by means of kinesthetic teaching, and robot interaction behavior by means of impedance shaping along the trajectory exploiting a wearable interface. Specifically, the wearable interface is designed to not affect the free motion of the operator, necessary to perform kinesthetic teaching, and it is based on the usage of surface electromyography (sEMG) and vibrotactile stimulation. In this way, we propose an intuitive robot programming framework for an offline robot trajectory and interaction behavior programming, according to which the operator will be able to plan interactions with the environment and humans. In this article, we report a preliminary experimental evaluation of the proposed system, in which an operator will teach a 7-degrees-of-freedom manipulator the execution of a task on a robotic wiring test-bed. In the experiment, the programming of requested compliance levels during the kinesthetic teaching of a trajectory is performed, and the reported results show that the provided wearable interface is successfully exploited by the operator. Finally, the experiment also demonstrates that the offline intuitive programming of trajectories and impedance levels can be exploited online for human-robot co-work.

ABSTRACTIntroduction:Secondary hyperparathyroidism (SHPT) represents a complication of chronic kidney disease (CKD). Vitamin D system is altered since early CKD, and vitamin D deficiency is an established trigger of SHPT. Although untreated SHPT may degenerate into tertiary hyperparathyroidism with detrimental consequences in advanced CKD, best treatments for counteracting SHPT from stage 3 CKD are still debated. Enthusiasm on prescription of vitamin D receptor activators (VDRA) in non-dialysis renal patients, has been mitigated by the risk of low bone turnover and positive calcium-phosphate balance. Nutritional vitamin D is now suggested as first-line therapy to treat SHPT with low 25(OH)D insufficiency. However, no high-grade evidence supports the best choice between ergocalciferol, cholecalciferol, and calcifediol (in its immediate or extended-release formulation).Areas covered:The review discusses available data on safety and efficacy of nutritional vitamin D, VDRA and nutritional therapy in replenishing 25(OH)D deficiency and counteracting SHPT in non-dialysis CKD patients.Expert opinion:Best treatment for low 25(OH)D and SHPT remains unknown, due to incomplete understanding of the best homeostatic, as mutable, adaptation of mineral metabolism to CKD progression. Nutritional vitamin D and nutritional therapy appear safest interventions, whenever contextualized with single-patient characteristics. VDRA should be restricted to uncontrolled SHPT by first-line therapy.

A fraction from normal human plasma inhibiting [Na.sup.+] -[K.sup.+] ATPase has been recently identified as lysophosphatidylcholine (LPC). The aim of this study was to investigate the existence of a relationship [...]

Myocardial blood flow (MBF) was measured using continuous inhalation of oxygen-15-labeled car. bon dioxide, and positron emission tomography before and after intravenous dipyridamole in 13 patients with syndrome X (angina pectoris, angiographically normal coronary arteries, positive exercise test and negative ergonovine test), 7 healthy subjects and 8 patients with 1-vessel coronary artery disease (CAD). In patients with syndrome X, baseline MBF was greater than in healthy subjects and patients with CAD (1.24 [+ or -] 0.27 vs 0.87 [+ or -] 0.07 and 1.03 [+ or -] 0.23 ml/g/min, respectively; p

MAY The backyard apple tree gets sad so soon, takes on a used-up, feather-duster look within a week. The ivy's spring reconnaissance campaign sends red feelers out and up and [...]