Kinetics of the mechanically induced ibuprofen-nicotinamide co-crystal formation by X-ray diffraction.

Mechanochemistry is drawing attention from the pharmaceutical industry given its potential for sustainable material synthesis and manufacture. Scaling mechanochemical processes to industrial level remains a challenge due to an incomplete understanding of their underlying mechanisms. We here show how time-resolved powder X-ray diffraction data, coupled with analytical kinetic modelling, provides a powerful approach to gain mechanistic insight into mechanochemical reactions.

A kinetic study of mechanically activated atom exchange: the effect of milling frequency and ball mass.

This study investigates the mechanochemical reaction of hydrogen isotope exchange between solid benzoic acid and liquid heavy water. The systematic change of milling conditions revealed that the reaction rate scales with the milling frequency and the mass of the milling balls. The ball size being always the same, faster reactions stem from the use of higher milling frequencies and heavier balls.

Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project.

Background: A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating.

Mechanochemically Induced Solid-State Transformations of Levofloxacin.

Levofloxacin hemihydrate (LVXh) is a complex fluoroquinolone drug that exists in both hydrated and anhydrous/dehydrated forms. Due to the complexity of such a compound, the primary aim of this study was to investigate the amorphization capabilities and solid-state transformations of LVXh when exposed to mechanical treatment using ball milling. Spray drying was utilized as a comparative method for investigating the capabilities of complete LVX amorphous (LVXam) formation.

Mechanochemical ignition of self-propagating reactions in equimolar Al-Ni powder mixtures and multilayers.

This work addresses a long standing question in the field of mechanochemistry, namely the role of mesostructure in the initiation of self-propagating high-temperature reactions in exothermic chemical systems, commonly referred to as ignition. In an attempt to find robust evidence in this regard, we compare the ignition behaviour of equimolar Al-Ni powder mixtures and equimolar Al-Ni multilayers. To achieve the best possible control of experimental conditions and allowing high reproducibility, we used elemental powders sieved in the range between 20 μm and 44 μm, and multilayers with bi-layer thickness between 10 nm and 800 nm.

Machine Learning-Supported Diagnosis of Small Blue Round Cell Sarcomas Using Targeted RNA Sequencing.

Small blue round cell sarcomas (SBRCSs) are a heterogeneous group of tumors with overlapping morphologic features but markedly varying prognosis. They are characterized by distinct chromosomal alterations, particularly rearrangements leading to gene fusions, whose detection currently represents the most reliable diagnostic marker. Ewing sarcomas are the most common SBRCSs, defined by gene fusions involving EWSR1 and transcription factors of the ETS family, and the most frequent non-EWSR1-rearranged SBRCSs harbor a CIC rearrangement.

Critical assessment of variant prioritization methods for rare disease diagnosis within the Rare Genomes Project.

Background: A major obstacle faced by rare disease families is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years, and causal variants are identified in under 50%. The Rare Genomes Project (RGP) is a direct-to-participant research study on the utility of genome sequencing (GS) for diagnosis and gene discovery.

Mechanochemical Reactions from Individual Impacts to Global Transformation Kinetics.

Typically induced by the mechanical processing of powders in ball mills, mechanochemical transformations are considered to result from the application of mechanical force to solid reactants. However, the undeniable deep connection between the dynamic compaction of powders during impacts and the overall transformation degree has yet to be disclosed. In the present work, we show that the square planar bis(dibenzoylmethanato)Ni coordination compound undergoes trimerization when its powder experiences even a single ball impact.

Mechanochemical effects underlying the mechanically activated catalytic hydrogenation of carbon monoxide.

In this work, we highlight and measure the intensity of mechanochemical effects at work in the hydrogenation of carbon monoxide by comparing the activity of a supported Co-Fe catalyst subjected, respectively, to ball milling and simple powder agitation. Paying due regard to the discontinuous nature of ball milling, we show that mechanochemical hydrogenation proceeds at significantly higher rate and disclose its connection with individual impacts. Experimental evidence suggests that the enhanced catalytic activity we observe can be ascribed to local processes affecting the amount of powder that gets involved in individual impacts.

Extending the Hammett correlation to mechanochemical reactions.

Using Raman monitoring and mechanochemistry-specific kinetic analysis, we find a correlation between the reaction probability and the Hammett constants in a model mechanochemical reaction of imine formation, indicating that the body of knowledge developed in physical-organic chemistry could be transferable to ball milling reactions in the solid state.

Mechanochemical reaction kinetics scales linearly with impact energy.

Inelastic collisions of the milling media in ball milling provide energy to the reaction mixture required for chemical transformations. However, movement of the milling media also results in physical mixing of reactants, which may enable a chemical reaction too. Separating the two contributions is challenging and gaining a direct insight into the purely mechanochemically driven reactivity is accordingly hindered.

Chemical effects induced by the mechanical processing of granite powder.

Starting from 1970s, the use of mechanical forces to induce chemical transformations has radically changed vast areas of metallurgy and materials science. More recently, mechanochemistry has expanded to core sectors of chemistry, showing the promise to deeply innovate chemical industry while enhancing its sustainability and competitiveness. We are still far, however, from unveiling the full potential of mechanical activation.

A phenomenological kinetic equation for mechanochemical reactions involving highly deformable molecular solids.

With its ability to enable solvent-free chemical reactions, mechanochemistry promises to open new and greener synthetic routes to chemical products of industrial interest. Its practical exploitation requires understanding the relationships between processing variables, powders' mechanical behaviour, and chemical reactivity. To this aim, rationalizing experimental kinetics is of paramount importance.

Kinetics of mechanochemical transformations.

The use of mechanical forces to activate and drive chemical transformations in solid particulate is attracting remarkable interest in the light of its promising application in a wide spectrum of strategic areas ranging from materials science to fine chemical synthesis and pharmaceutical ingredient production. The capability of enabling solventless processes and fabricating unique materials inaccessible otherwise has made mechanochemistry one of the ten chemical innovations with the highest potential of changing the world. As in the past, so again now, the development of reliable technologies based on mechanochemical transformations cannot be separated from the understanding of the underlying mechanisms, their description and their control.

Prebiotic Therapy with Inulin Associated with Low Protein Diet in Chronic Kidney Disease Patients: Evaluation of Nutritional, Cardiovascular and Psychocognitive Parameters.

A relationship between dysbiotic gut microbiome and chronic kidney disease (CKD) has been recently documented; it contributes to CKD-related complications, including cardiovascular disease. Aim: We tested how a low-protein diet (LPD)-with or without oral inulin supplementation as a prebiotic-modulates some inflammatory, atherosclerosis and endothelial dysfunction indices and nutritional markers, as well as psychocognitive functions in CKD patients. We conducted a prospective, case-control study on CKD patients on conservative therapy, divided in two groups: the intervention group treated with LPD (0.

Urinary [TIMP-2] × [IGFBP7] and serum procalcitonin to predict and assess the risk for short-term outcomes in septic and non-septic critically ill patients.

Background: Biomarkers can play a critical role by facilitating diagnosis and stratification of disease, as well as assessment or prediction of disease severity. Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 product ([TIMP-2] × [IGFBP7]) predict the development and progression of AKI and recently procalcitonin (PCT), a widely used biomarker for sepsis diagnosis and management, has been associated with AKI occurrence in ICU patients. To assess combinations of [TIMP-2] × [IGFBP7] and PCT results for prediction and risk stratification of short-term outcomes in septic and non-septic patients, a retrospective cohort analysis of critically ill patients was performed in a multidisciplinary ICU.

α-lipoic acid in patients with autosomal dominant polycystic kidney disease.

Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease characterized by multiple and bilateral cystic dilation of renal tubules. Hypertension, endothelial dysfunction, systemic inflammation, and accelerated atherosclerosis are alterations found at a very early stage of the disease and are responsible for increasing both cardiovascular risks and progression toward end-stage renal disease. The aim of the study was to evaluate the effects of the use of 1.

The Relationships between Physical Activity, Self-Efficacy, and Quality of Life in People with Multiple Sclerosis.

Regular physical activity (PA) can enhance the physical and mental health of people with Multiple Sclerosis (MS) because of its impact on muscular strength, mobility, balance, walking, fatigue, pain and health-related quality of life (HRQoL). Previous studies have hypothesized that the relationship between PA and HRQoL is mediated by self-efficacy. The aim of this research is to evaluate whether self-efficacy in goal setting and self-efficacy in the management of symptoms, mediate the relationship between PA and HRQoL, in a similar way to exercise self-efficacy.

Routine Adoption of Urinary [IGFBP7]∙[TIMP-2] to Assess Acute Kidney Injury at Any Stage 12 hours After Intensive Care Unit Admission: a Prospective Cohort Study.

The urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]∙[IGFBP7]) have been introduced to improve risk prediction of severe acute kidney injury (AKI) within 12 hours of measurement. We performed a prospective cohort study to evaluate if the predictive value of [TIMP-2]∙[IGFBP7] for AKI might continue after 12 hours. We enrolled 442 critically ill adult patients from June to December 2016.

Phenomenological Inferences on the Kinetics of a Mechanically Activated Knoevenagel Condensation: Understanding the "Snowball" Kinetic Effect in Ball Milling.

We focus on understanding the kinetics of a mechanically activated Knoevenagel condensation conducted in a ball mill, that is characterized by sigmoidal kinetics and the formation of a rubber-like cohesive intermediate state coating the milling ball. The previously described experimental findings are explained using a phenomenological kinetic model. It is assumed that reactants transform into products already at the very first collision of the ball with the wall of the jar.

Processing and Investigation Methods in Mechanochemical Kinetics.

The present work focuses on the challenges that emerge in connection with the kinetics of mechanically activated transformations. This is an important topics to comprehend to enable the full exploitation of mechanical processing in a broad spectrum of areas related to chemistry and materials science and engineering. Emerging challenges involve a number of facets regarding materials and material properties, working principles of ball mills and milling conditions, and local changes occurring in series in processed materials.

Development and validation of quick Acute Kidney Injury-score (q-AKI) to predict acute kidney injury at admission to a multidisciplinary intensive care unit.

AKI is associated with increased risk of death, prolonged length of stay and development of de-novo chronic kidney disease. The aim of our study is the development and validation of prediction models to identify the risk of AKI in ICU patients up to 7 days. We retrospectively recruited 692 consecutive patients admitted to the ICU at San Bortolo Hospital (Vicenza, Italy) from 1 June 2016 to 31 March 2017: 455 patients were treated as the derivation group and 237 as the validation group.

Neurological, psychological, and cognitive disorders in patients with chronic kidney disease on conservative and replacement therapy.

Chronic kidney disease (CKD) is a highly prevalent condition in the world. Neurological, psychological, and cognitive disorders, related to CKD, could contribute to the morbidity, mortality, and poor quality of life of these patients. The aim of this study was to assess the neurological, psychological, and cognitive imbalance in patients with CKD on conservative and replacement therapy.

Tenofovir-Related Nephropathies in HIV-Infected Patients.

Background: The number of human immunodeficiency virus (HIV)-infected patients has increased significantly, although the number of deaths due to HIV and acquired immunodeficiency syndrome (AIDS) has dramatically reduced. Highly active antiretroviral therapy (HAART) has increased not only survival but also the risk of deaths caused by other diseases or by long-term side effects of these drugs.

Aim: The aim of this study is to evaluate the nephrotoxicity of one of the most common anti-retroviral drugs, tenofovir disoproxil fumarate (TDF).