Protein-caloric-restriction diet during lactation programs lean phenotype and improves the antioxidative system in adult female rat offspring.

Nutritional insults early in life, such as during the suckling phase, are associated with phenotypic alterations and promote adverse permanent effects that impair the capacity to maintain energy balance in adulthood. This study aimed to evaluate the long-term effects of a low-protein (LP) diet during lactation on the metabolism and antioxidant systems of adult female rat offspring. Dams were fed a low-protein diet (4% protein) during the first two weeks of lactation or a normal-protein (NP) diet (20% protein) during the entire lactation period.

Protocolized Natriuresis-Guided Decongestion Improves Diuretic Response: The Multicenter ENACT-HF Study.

Background: The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However, there are limited data to support this recommendation. The ENACT-HF study (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure and signs of volume overload.

Corrigendum to "Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications".

[This corrects the article DOI: 10.1155/2021/9996193.].

Protein restriction during lactation causes transgenerational metabolic dysfunction in adult rat offspring.

Introduction: Protein restriction during lactation can induce metabolic dysfunctions and has a huge impact on the offspring's phenotype later in its life. We tested whether the effects of a maternal low-protein diet (LP) in rats can be transmitted to the F2 generation and increase their vulnerability to dietary insults in adulthood.

Methods: Female Wistar rats (F0) were fed either a low-protein diet (LP; 4% protein) during the first 2 weeks of lactation or a normal-protein diet (NP; 23% protein).

Challenges and Opportunities With Routinely Collected Data on the Utilization of Cancer Medicines. Perspectives From Health Authority Personnel Across 18 European Countries.

Rising expenditure for new cancer medicines is accelerating concerns that their costs will become unsustainable for universal healthcare access. Moreover, early market access of new oncology medicines lacking appropriate clinical evaluation generates uncertainty over their cost-effectiveness and increases expenditure for unknown health gain. Patient-level data can complement clinical trials and generate better evidence on the effectiveness, safety and outcomes of these new medicines in routine care.

Dealing With Immunoglobulin Shortages: A Rationalization Plan From Evidence-Based and Data Collection.

Background: The demand and consumption of immunoglobulins (IgGs) are growing, and there are many difficulties in obtaining supplies. The aim of the study was to analyze the evolution of IgG consumption and cost over a decade, describe the measures implemented for clinical management in the context of regional public health system, and evaluate the initial impact of these measures.

Methods: We performed a retrospective longitudinal study including patients of all public health systems in Catalonia.

Rationale and Design of the Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure Study.

Aims: Although acute heart failure (AHF) with volume overload is treated with loop diuretics, their dosing and type of administration are mainly based upon expert opinion. A recent position paper from the Heart Failure Association (HFA) proposed a step-wise pharmacologic diuretic strategy to increase the diuretic response and to achieve rapid decongestion. However, no study has evaluated this protocol prospectively.

Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications.

Background: Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs.

The Current Situation Regarding Long-Acting Insulin Analogues Including Biosimilars Among African, Asian, European, and South American Countries; Findings and Implications for the Future.

Diabetes mellitus rates continue to rise, which coupled with increasing costs of associated complications has appreciably increased global expenditure in recent years. The risk of complications are enhanced by poor glycaemic control including hypoglycaemia. Long-acting insulin analogues were developed to reduce hypoglycaemia and improve adherence.

Intracellular Redox-Modulated Pathways as Targets for Effective Approaches in the Treatment of Viral Infection.

Host-directed therapy using drugs that target cellular pathways required for virus lifecycle or its clearance might represent an effective approach for treating infectious diseases. Changes in redox homeostasis, including intracellular glutathione (GSH) depletion, are one of the key events that favor virus replication and contribute to the pathogenesis of virus-induced disease. Redox homeostasis has an important role in maintaining an appropriate Th1/Th2 balance, which is necessary to mount an effective immune response against viral infection and to avoid excessive inflammatory responses.

Activation of NRF2 and ATF4 Signaling by the Pro-Glutathione Molecule I-152, a Co-Drug of -Acetyl-Cysteine and Cysteamine.

I-152 combines two pro-glutathione (GSH) molecules, namely N-acetyl-cysteine (NAC) and cysteamine (MEA), to improve their potency. The co-drug efficiently increases/replenishes GSH levels in vitro and in vivo; little is known about its mechanism of action. Here we demonstrate that I-152 not only supplies GSH precursors, but also activates the antioxidant kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 (KEAP1/NRF2) pathway.

Redox homeostasis as a target for new antimycobacterial agents.

Despite early treatment with antimycobacterial combination therapy, drug resistance continues to emerge. Maintenance of redox homeostasis is essential for Mycobacterium avium (M. avium) survival and growth.

I-152, a supplier of N-acetyl-cysteine and cysteamine, inhibits immunoglobulin secretion and plasma cell maturation in LP-BM5 murine leukemia retrovirus-infected mice by affecting the unfolded protein response.

Excessive production of immunoglobulins (Ig) causes endoplasmic reticulum (ER) stress and triggers the unfolded protein response (UPR). Hypergammaglobulinemia and lymphadenopathy are hallmarks of murine AIDS that develops in mice infected with the LP-BM5 murine leukemia retrovirus complex. In these mice, Th2 polarization and aberrant humoral response have been previously correlated to altered intracellular redox homeostasis.

Association of Microvesicles With Graft Patency in Patients Undergoing CABG Surgery.

Background: Graft patency is one of the major determinants of long-term outcome following coronary artery bypass graft surgery (CABG). Biomarkers, if indicative of the underlying pathophysiological mechanisms, would suggest strategies to limit graft failure. The prognostic value of microvesicles (MVs) for midterm graft patency has never been tested.

Time to Review Authorisation and Funding for New Cancer Medicines in Europe? Inferences from the Case of Olaratumab.

The potential benefits of early patient access to new medicines in areas of high unmet medical need are recognised, but uncertainties concerning effectiveness, safety and added value when new medicines are authorised, and subsequently funded based on initial preliminary data only, have important implications. In 2016 olaratumab received accelerated conditional approval from both the European Medicines Agency and the US Food and Drug Administration for the treatment of soft-tissue sarcoma, based on the claims of a substantial reduction in the risk of death with an 11.8-month improvement in median overall survival in a phase II trial in combination with doxorubicin vs.

Call for Action: Benzodiazepine Prescription Prevalence Analysis Shows Off-Label Prescription in One in Eleven Citizens.

Objective: Benzodiazepines have a good safety profile. Nevertheless, off-label use of these drugs may increase the risk of falls, dependence, and memory loss. Off-label prescription use is not highly prevalent.

Boosting GSH Using the Co-Drug Approach: I-152, a Conjugate of -acetyl-cysteine and β-mercaptoethylamine.

Glutathione (GSH) has poor pharmacokinetic properties; thus, several derivatives and biosynthetic precursors have been proposed as GSH-boosting drugs. I-152 is a conjugate of -acetyl-cysteine (NAC) and -acetyl-β-mercaptoethylamine (SMEA) designed to release the parent drugs (i.e.

Proposal for a regulation on health technology assessment in Europe - opinions of policy makers, payers and academics from the field of HTA.

In January 2018 the European Commission published a Proposal for a Regulation on Health Technology Assessment (HTA): 'Proposal for a Regulation on health technology assessment and amending Directive 2011/24/EU'. A number of stakeholders, including some Member States, welcomed this initiative as it was considered to improve collaboration, reduce duplication and improve efficiency. There were however a number of concerns including its legal basis, the establishment of a single managing authority, the preservation of national jurisdiction over HTA decision-making and the voluntary/mandatory uptake of joint assessments by Member States.

Barriers for Access to New Medicines: Searching for the Balance Between Rising Costs and Limited Budgets.

There is continued unmet medical need for new medicines across countries especially for cancer, immunological diseases, and orphan diseases. However, there are growing challenges with funding new medicines at ever increasing prices along with funding increased medicine volumes with the growth in both infectious diseases and non-communicable diseases across countries. This has resulted in the development of new models to better manage the entry of new medicines, new financial models being postulated to finance new medicines as well as strategies to improve prescribing efficiency.

Novel insights into pericarp, protein body globoids of aleurone layer, starchy granules of three cereals gained using atomic force microscopy and environmental scanning electronic microscopy.

In this study, we applied Environmental Scanning Electron Microscopy-Energy Dispersive Spectroscopy (ESEM-EDS) and Atomic Force Microscopy (AFM) analysis to three different cereal caryopses: barley, oat and einkorn wheat. The morphological structures, chemical elemental composition and surface characteristics of the three cereals were described. Regarding the morphology, barley showed the thickest pericarp, providing a strong barrier digestion and absorption of nutrients.

Impact of angiotensin-converting enzyme inhibition on platelet tissue factor expression in stroke-prone rats.

Objective: Hypertension is a well known risk factor for thrombotic events such as myocardial infarction and stroke. Platelets express tissue factor (TF), the key activator of blood coagulation and thrombus formation. The number of TF-positive platelets increases in pathological conditions characterized by thrombotic complications but whether this occurs in hypertension is unknown.

Assessment of patient functional performance in different knee arthroplasty designs during unconstrained squat.

Background: In this paper, squat named by Authors because performed without constrains related to feet position, speed, knee maximum angle to be reached, was tested as motor task revealing differences in functional performance after knee arthroplasty. It involves large joints ranges of motion, does not compromise joint safety and requires accurate control strategies to maintain balance.

Methods: Motion capture techniques were used to study squat on a healthy control group (CTR) and on three groups, each characterised by a specific knee arthroplasty design: a Total Knee Arthroplasty (TKA), a Mobile Bearing and a Fixed Bearing Unicompartmental Knee Arthroplasty (respectively MBUA and FBUA).

Optimizing Management of Heart Failure by Using Echo and Natriuretic Peptides in the Outpatient Unit.

Chronic heart failure (HF) is an important public health problem and is associated with high morbidity, high mortality, and considerable healthcare costs. More than 90% of hospitalizations due to worsening HF result from elevations of left ventricular (LV) filling pressures and fluid overload, which are often accompanied by the increased synthesis and secretion of natriuretic peptides (NPs). Furthermore, persistently abnormal LV filling pressures and a rise in NP circulating levels are well known indicators of poor prognosis.