Factors and Mechanisms of Thyroid Hormone Activity in the Brain: Possible Role in Recovery and Protection.

Thyroid hormones (THs) are essential in normal brain development, and cognitive and emotional functions. THs act through a cascade of events including uptake by the target cells by specific cell membrane transporters, activation or inactivation by deiodinase enzymes, and interaction with nuclear thyroid hormone receptors. Several thyroid responsive genes have been described in the developing and in the adult brain and many studies have demonstrated a systemic or local reduction in TH availability in neurologic disease and after brain injury. In this review, the main factors and mechanisms associated with the THs in the normal and damaged brain will be evaluated in different regions and cellular contexts. Furthermore, the most common animal models used to study the role of THs in brain damage and cognitive impairment will be described and the use of THs as a potential recovery strategy from neuropathological conditions will be evaluated. Finally, particular attention will be given to the link observed between TH alterations and increased risk of Alzheimer's Disease (AD), the most prevalent neurodegenerative and dementing condition worldwide.

Assessment of the Psychometric Characteristics of the Italian Version of the Nurse Manager Actions Scale.

Nurse managers play a vital role in healthcare organizations, wielding the ability to substantially enhance work environments, foster nurses' autonomy, and bolster retention within workplaces. In this context, this study focuses on the Nurse Manager Actions scale, aiming to evaluate its items' scalability as well as the scale's validity and reliability among nurses and nurse managers operating within the Italian healthcare context. The study protocol was not registered. To ensure linguistic and cultural alignment, an iterative and collaborative translation process was undertaken. Subsequently, a multi-center cross-sectional design was adopted. Using a web-survey approach, data were collected among 683 nurses and 188 nurse managers between August 2022 and January 2023. The Nurse Manager Actions scale was found to be a valid and reliable instrument in Italian after a Mokken Scale Analysis. For nurses (HT= 0.630, Molenaar-Sijtsma rho = 0.890), the scale included 6 items, while 11 items were confirmed for nurse managers (HT= 0.620, Molenaar-Sijtsma rho = 0.830). Nurse Manager Actions scale scores were correlated with increased satisfaction and decreased intention to leave for both nurses and nurse managers. The employed validation process enhanced the scale validity for use in Italy and provided a model for other researchers to follow when assessing similar measures in different populations. Measuring and empowering nurse manager actions in work contexts is essential to improve the general well-being and retention of nurses, especially in the current nursing shortage.

Psychometric Properties of the Italian Version of the Leader Member Exchange Scale (LMX-7): A Validation Study.

For decades, scholars have studied leader-member exchange (LMX) relationships to understand and explain the effects of leadership on follower attitudes and performance outcomes within work settings. One available instrument to measure these aspects is the LMX-7 scale. This measurement has been widely used in empirical studies, but its psychometric properties have been poorly explored. The aim of this study was to test the psychometric characteristics (content, structural and construct validity, and reliability) of the Italian version of the LMX-7 scale and to support its cultural adaptation. We used a cross-sectional multi-center design. The forward-backward translation process was used to develop the Italian version of the scale. The scale was administered through an online survey to 837 nurses and nurse managers working in different settings. The factorial structure was tested using both exploratory and confirmatory factor analyses (EFA and CFA), and reliability was evaluated using Cronbach's alpha. For the construct validity, we used hypothesis testing and differentiation by known groups. The Italian version of the LMX-7 scale presented one dimension. All the psychometric tests performed confirmed its validity and suggested its usefulness for future research.

Nrf2-Mediated Antioxidant Defense and Thyroid Hormone Signaling: A Focus on Cardioprotective Effects.

Thyroid hormones (TH) perform a plethora of actions in numerous tissues and induce an overall increase in metabolism, with an augmentation in energy demand and oxygen expenditure. Oxidants are required for normal thyroid-cell proliferation, as well as for the synthesis of the main hormones secreted by the thyroid gland, triiodothyronine (T3) and thyroxine (T4). However, an uncontrolled excess of oxidants can cause oxidative stress, a major trigger in the pathogenesis of a broad spectrum of diseases, including inflammation and cancer. In particular, oxidative stress is implicated in both hypo- and hyper-thyroid diseases. Furthermore, it is important for the TH system to rely on efficient antioxidant defense, to maintain balance, despite sustained tissue exposure to oxidants. One of the main endogenous antioxidant responses is the pathway centered on the nuclear factor erythroid 2-related factor (Nrf2). The aim of the present review is to explore the multiple links between Nrf2-related pathways and various TH-associated conditions. The main aspect of TH signaling is described and the role of Nrf2 in oxidant-antioxidant homeostasis in the TH system is evaluated. Next, the antioxidant function of Nrf2 associated with oxidative stress induced by TH pathological excess is discussed and, subsequently, particular attention is given to the cardioprotective role of TH, which also acts through the mediation of Nrf2. In conclusion, the interaction between Nrf2 and most common natural antioxidant agents in altered states of TH is briefly evaluated.

Evaluation of Standard Precautions Compliance Instruments: A Systematic Review Using COSMIN Methodology.

BACKGROUND: Standard precautions (SPs) are first-line strategies with a dual goal: to protect health care workers from occupational contamination while providing care to infected patients and to prevent/reduce health care-associated infections (HAIs). This study aimed at (1) identifying the instruments currently available for measuring healthcare professionals' compliance with standard precautions; (2) evaluating their measurement properties; and (3) providing sound evidence for instrument selection for use by researchers, teachers, staff trainers, and clinical tutors. METHODS: We carried out a systematic review to examine the psychometric properties of standard precautions self-assessment instruments in conformity with the COSMIN guidelines. The search was conducted on the databases PubMed, CINAHL, and APA PsycInfo. RESULTS: Thirteen instruments were identified. These were classified into four categories of tools assessing: compliance with universal precautions, adherence to standard precautions, compliance with hand hygiene, and adherence to transmission-based guidelines and precautions. The psychometric properties of instruments and methodological approaches of the included studies were often not satisfactory. Only four instruments were classified as high-quality measurements. CONCLUSIONS: The available instruments that measure healthcare professionals' compliance with standard precautions are of low-moderate quality. It is necessary that future research completes the validation processes undertaken for long-established and newly developed instruments, using higher-quality methods and estimating all psychometric properties.

Vitamin D Determinants, Status, and Antioxidant/Anti-inflammatory-Related Effects in Cardiovascular Risk and Disease: Not the Last Word in the Controversy.

Beyond its key role in calcium homeostasis, vitamin D has been found to significantly affect the cardiovascular (CV) system. In fact, low vitamin D levels have been associated with increased CV risk, as well as increased CV morbidity and mortality. The majority of effects of this molecule are related directly or indirectly to its antioxidative and anti-inflammatory properties. Generally, vitamin D insufficiency is considered for 25-hydroxyvitamin D (25(OH)D) levels between 21-29 ng/mL (corresponding to 52.5-72.5 nmol/L), deficiency as 25(OH)D levels less than 20 ng/mL (<50 nmol/L), and extreme deficiency as 25(OH)D less than 10 ng/mL (<25 nmol/L). However, the definition of an optimal vitamin D status, as defined by 25(OH)D, remains controversial for many extra-bone conditions, including CV disease. In this review, confounding factors affecting the 25(OH)D measurement and status will be discussed. In particular, available evidence on the mechanism and role of vitamin D in relation to CV risk and disease through its antioxidant effect will be reported, also facing the aspect regarding the debate on the minimum blood 25(OH)D level required to ensure optimal CV health.

Appraisal and Evaluation of the Learning Environment Instruments of the Student Nurse: A Systematic Review Using COSMIN Methodology.

BACKGROUND: Nursing education consists of theory and practice, and student nurses' perception of the learning environment, both educational and clinical, is one of the elements that determines the success or failure of their university study path. This study aimed to identify the currently available tools for measuring the clinical and educational learning environments of student nurses and to evaluate their measurement properties in order to provide solid evidence for researchers, educators, and clinical tutors to use in the selection of tools. METHODS: We conducted a systematic review to evaluate the psychometric properties of self-reported learning environment tools in accordance with the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) Guidelines of 2018. The research was conducted on the following databases: PubMed, CINAHL, APA PsycInfo, and ERIC. RESULTS: In the literature, 14 instruments were found that evaluate both the traditional and simulated clinical learning environments and the educational learning environments of student nurses. These tools can be ideally divided into first-generation tools developed from different learning theories and second-generation tools developed by mixing, reviewing, and integrating different already-validated tools. CONCLUSION: Not all the relevant psychometric properties of the instruments were evaluated, and the methodological approaches used were often doubtful or inadequate, thus threatening the instruments' external validity. Further research is needed to complete the validation processes undertaken for both new and already developed instruments, using higher-quality methods and evaluating all psychometric properties.

Thyroid Dysfunction and COVID-19: The Emerging Role of Selenium in This Intermingled Relationship.

COVID-19 represents a worldwide public health emergency, and, beyond the respiratory symptoms characterizing the classic viral disease, growing evidence has highlighted a possible reciprocal relationship between SARS-CoV-2 infection and thyroid dysfunction. The updated data discussed in this review suggests a role of SARS-CoV-2 infection on the thyroid gland, with multiple thyroid pictures described. Conversely, no conclusion can be drawn on the association between pre-existing thyroid disease and increased risk of SARS-CoV-2 infection. In this scenario, selenium (Se), an essential trace element critical for thyroid function and known as an effective agent against viral infections, is emerging as a potential novel therapeutic option for the treatment of COVID-19. Large multicentre cohort studies are required to elucidate the mechanisms underlying thyroid dysfunction during or following recovery from COVID-19, including Se status. Meanwhile, clinical trials should be performed to evaluate whether adequate intake of Se can help address COVID-19 in Se-deficient patients, also avoiding thyroid complications that can contribute to worsening outcomes during infection.

Cerium oxide nanoparticles administration during machine perfusion of discarded human livers: A pilot study.

The combined approach of ex situ normothermic machine perfusion (NMP) and nanotechnology represents a strategy to mitigate ischemia/reperfusion injury in liver transplantation (LT). We evaluated the uptake, distribution, and efficacy of antioxidant cerium oxide nanoparticles (nanoceria) during normothermic perfusion of discarded human livers. A total of 9 discarded human liver grafts were randomized in 2 groups and underwent 4 h of NMP: 5 grafts were treated with nanoceria conjugated with albumin (Alb-NC; 50 µg/ml) and compared with 4 untreated grafts. The intracellular uptake of nanoceria was analyzed by electron microscopy (EM) and inductively coupled plasma-mass spectrometry (ICP-MS). The antioxidant activity of Alb-NC was assayed in liver biopsies by glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) assay, telomere length, and 4977-bp common mitochondrial DNA deletion (mtDNA4977 deletion). The cytokine profile was evaluated in perfusate samples. EM and ICP-MS confirmed Alb-NC internalization, rescue of mitochondrial phenotype, decrease of lipid droplet peroxidation, and lipofuscin granules in the treated grafts. Alb-NC exerted an antioxidant activity by increasing GSH levels (percentage change: +94% ± 25%; p = 0.01), SOD (+17% ± 4%; p = 0.02), and CAT activity (51% ± 23%; p = 0.03), reducing the occurrence of mtDNA4977 deletion (-67.2% ± 11%; p = 0.03), but did not affect cytokine release. Alb-NC during ex situ perfusion decreased oxidative stress, upregulating graft antioxidant defense. They could be a tool to improve quality grafts during NMP and represent an antioxidant strategy aimed at protecting the graft against reperfusion injury during LT.

Selenium: An Element of Life Essential for Thyroid Function.

Selenium (Se), a microelement essential for life, is critical for homeostasis of several critical functions, such as those related to immune-endocrine function and signaling transduction pathways. In particular, Se is critical for the function of the thyroid, and it is particularly abundant in this gland. Unfortunately, Se deficiency is a very common condition worldwide. Supplementation is possible, but as Se has a narrow safety level, toxic levels are close to those normally required for a correct need. Thus, whether the obtaining of optimal selenium concentration is desirable, the risk of dangerous concentrations must be equally excluded. This review addressed the contribution by environment and food intake on Se circulating levels (e.g., geographical factors, such as soil concentration and climate, and different quantities in food, such as nuts, cereals, eggs, meat and fish) and effects related to its deficiency or excess, together with the role of selenium and selenoproteins in the thyroid pathophysiology (e.g., Hashimoto's thyroiditis and Graves' disease).

Main Factors Involved in Thyroid Hormone Action.

The thyroid hormone receptors are the mediators of a multitude of actions by the thyroid hormones in cells. Most thyroid hormone activities require interaction with nuclear receptors to bind DNA and regulate the expression of target genes. In addition to genomic regulation, thyroid hormones function via activation of specific cytosolic pathways, bypassing interaction with nuclear DNA. In the present work, we reviewed the most recent literature on the characteristics and roles of different factors involved in thyroid hormone function in particular, we discuss the genomic activity of thyroid hormone receptors in the nucleus and the functions of different thyroid hormone receptor isoforms in the cytosol. Furthermore, we describe the integrin αvß3-mediated thyroid hormone signaling pathway and its rapid nongenomic action in the cell. We furthermore reviewed the thyroid hormone transporters enabling the uptake of thyroid hormones in the cell, and we also include a paragraph on the proteins that mediate thyroid receptors' shuttling from the nucleus to the cytosol.

Hypovitaminosis D and Low T3 Syndrome: A Link for Therapeutic Challenges in Patients with Acute Myocardial Infarction.

BACKGROUND AND AIMS: Vitamin D counteracts the reduction in the peripheral conversion of tiroxine (T4) into triiodothyronine (T3), which is the mechanism of low T3 syndrome (LT3) in acute myocardial infarction (AMI). The aim of this study was to assess the relationship between LT3 and hypovitaminosis D in AMI patients. METHODS AND RESULTS: One hundred and twenty-four AMI patients were enrolled. Blood samples were taken at admission, and at 3, 12, 24, 48, and 72 h after admission. LT3 was defined as a value of fT3 ≤ 2.2 pg/mL, occurring within 3 days of hospital admission. Levels were defined as follows: sufficiency as a value of ±30 ng/mL, vitamin D insufficiency as 25-hydroxyvitamin D (25(OH)D) between 21 and 29 ng/mL, deficiency in 25(OH)D as below 20 ng/mL, and severe deficiency as values under 10 ng/mL. The percentage of subjects with severe 25(OH)D deficiency was significantly higher in the LT3 group (33% vs. 13%, p < 0.01). When LT3S was evaluated as a dependent variable, severe 25(OH)D deficiency (OR 2.6: 95%CI 1-6.7, p < 0.05) remained as an independent determinant after logistic multivariate adjustment together with age (>69 yrs, 50th percentile; OR 3.4, 95% CI 1.3-8.3, p < 0.01), but not female gender (OR 1.7, 95% CI 0.7-4.2, p = ns). CONCLUSIONS: This pilot study shows a relationship between hypovitaminosis D and LT3 in AMI patients. This association opens potential therapeutic challenges concerning the restoration of euthyroidism through vitamin D administration, together with the normalization of hypovitaminosis.

Vitamin D, Thyroid Hormones and Cardiovascular Risk: Exploring the Components of This Novel Disease Triangle.

The role of thyroid hormones (THs) in the cardiovascular (CV) system, through several direct and indirect effects is recognized. Even very small modification in TH levels (as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome) may adversely affect the CV system, whereas thyroid hormones benefit the CV system and improve the prognosis. There is also evidence of vitamin D effects on cardiometabolic disease (e.g., through modulation of endothelial and smooth muscle cell activity, renin-angiotensin-aldosterone system, nitric oxide, oxidative stress, and inflammatory response), as well as an association between vitamin D [25(OH)D] deficiency and autoimmune thyroid diseases or cancer, and a relationship between vitamin D concentration and titers of antibodies and thyroid autoimmunity replacement. Interestingly, experimental data indicate a direct effect of vitamin D on Type 2 deiodinase expression causing subsequential peripheral conversion of T4 into T3. However, the functional links among THs, vitamin D and the cardiovascular system, and clinical effects of coexisting abnormalities in this new troublesome triad, have not yet been reviewed. The main aim of this review is to discuss pathophysiology of this relationship, proposing new mechanistic insights involving vitamin D in the modulation of cardiometabolic disease and thyroid profile.

Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions.

Thyroid hormone (TH) signaling is strictly regulated by iodothyronine deiodinase activity, which both preserves the circulating levels of the biologically active triiodothyronine (T3) and regulates TH homeostasis at the local level, in a cell- and time-dependent manner. Three deiodinases have been identified-namely iodothyronine deiodinase 1 (DIO1), DIO2, and DIO3-that differ in their catalytic properties and tissue distribution. The deiodinases represent a dynamic system that changes in the different stages of life according to their functions and roles in various cell types and tissues. Deiodinase activity at the tissue level permits cell-targeted fine regulation of TH homeostasis, mediating the activation (DIO1 and DIO2) and inactivation (DIO3) of THs. Deiodinase homeostasis is the driving force that leads T3-target cells towards customized TH signaling, which takes into account both the hormonal circulating levels and the tissue-specific response. This review analyzes the complex role of deiodinases in physiological and pathological contexts, exploring new challenges and opportunities deriving from a deeper knowledge of the dynamics underlying their roles and functions.

H2S as a Bridge Linking Inflammation, Oxidative Stress and Endothelial Biology: A Possible Defense in the Fight against SARS-CoV-2 Infection?

The endothelium controls vascular homeostasis through a delicate balance between secretion of vasodilators and vasoconstrictors. The loss of physiological homeostasis leads to endothelial dysfunction, for which inflammatory events represent critical determinants. In this context, therapeutic approaches targeting inflammation-related vascular injury may help for the treatment of cardiovascular disease and a multitude of other conditions related to endothelium dysfunction, including COVID-19. In recent years, within the complexity of the inflammatory scenario related to loss of vessel integrity, hydrogen sulfide (H2S) has aroused great interest due to its importance in different signaling pathways at the endothelial level. In this review, we discuss the effects of H2S, a molecule which has been reported to demonstrate anti-inflammatory activity, in addition to many other biological functions related to endothelium and sulfur-drugs as new possible therapeutic options in diseases involving vascular pathobiology, such as in SARS-CoV-2 infection.

Oxidative Stress Biomarkers in the Relationship between Type 2 Diabetes and Air Pollution.

The incidence and prevalence of type 2 diabetes have increased in the last decades and are expected to further grow in the coming years. Chronic hyperglycemia triggers free radical generation and causes increased oxidative stress, affecting a number of molecular mechanisms and cellular pathways, including the generation of advanced glycation end products, proinflammatory and procoagulant effects, induction of apoptosis, vascular smooth-muscle cell proliferation, endothelial and mitochondrial dysfunction, reduction of nitric oxide release, and activation of protein kinase C. Among type 2 diabetes determinants, many data have documented the adverse effects of environmental factors (e.g., air pollutants) through multiple exposure-induced mechanisms (e.g., systemic inflammation and oxidative stress, hypercoagulability, and endothelial and immune responses). Therefore, here we discuss the role of air pollution in oxidative stress-related damage to glycemic metabolism homeostasis, with a particular focus on its impact on health. In this context, the improvement of new advanced tools (e.g., omic techniques and the study of epigenetic changes) may provide a substantial contribution, helping in the evaluation of the individual in his biological totality, and offer a comprehensive assessment of the molecular, clinical, environmental, and epidemiological aspects.

Nursing in Albania: A Catalytic Force in Transforming Health Professionals and Health Care.

PURPOSE: Transitions in nursing education and professionalism that align with global nursing standards are elucidated as critical success factors in transforming health professionals and health care in Albania. Progressive educational and regulatory pathways throughout the 2000s (1999-2020) are emphasized for their impact on the Albanian health system, including the achievement of universal healthcare coverage. METHODS: Data collected by the Ministry of Health and Sport and the Regulatory Authority for nursing and other healthcare professions in Albania were analyzed and outcomes explicated with regard to Albania's major health challenges. DISCUSSION AND CONCLUSIONS: Three milestones affirmed nursing as a driving force in the Albanian healthcare system: (a) nurses constitute the largest health professional workforce via a nurse-patient ratio of 1:400 in contrast to a physician-patient ratio of 1:2,500; (b) nurses are frontline care providers via clinical leadership in the management of primary healthcare centers, which ensure universal healthcare coverage; and (c) nurses are first responders via their presence and compassionate caring in the primary healthcare centers, including making critical shifts in converting primary healthcare centers to urgent care centers as needed. CLINICAL RELEVANCE: Nursing advancements have implicated quality care and professionalism in Albania across the health professions via three critical pathways: (a) health professional education at a university degree level for entry into practice (since 1999), which was prompted by and driven by nursing's quest to be a self-regulated profession (achieved in 2007); (b) healthcare global standards sparked by nursing's mandate toward professional autonomy, as achieved via regulatory procedures and policies; and (c) interprofessional healthcare initiatives that serve as collaborative platforms for innovative educational, clinical, and research projects.

Thyroid hormone deiodinases response in brain of spontaneausly hypertensive rats after hypotensive effects induced by mandibular extension.

PURPOSE: The deiodinases activate or inactivate the thyroid hormones (TH) in virtually all tissues in both physiological and pathological conditions. The three deiodinases, DIO1, DIO2, and DIO3, have different catalytic functions and regulate TH tissue distribution. The aim of the present study was to evaluate the modulation of gene expression of the deiodinases and TH transporters and protein levels of DIO1 in parietal and frontal areas of cerebral cortex of spontaneously hypertensive rats (SHRs), after two successive mandibular extensions (ME). METHODS: ME was performed on anesthetized rats by a dilatator appropriately designed and real-time PCR and western blotting techniques were employed for gene expression and protein level study. RESULTS: Mean blood pressure (MBP) significantly decreased in 2ME-treated rats when compared to sham-operated rats (p < 0.001) and this decrease lasted for the entire observation period. In gene expression analysis, in 2ME-treated rats we did not observe any significant variation of DIO1 and DIO3 with respect to the sham-operated rats. Differently, DIO2 gene expression significantly increased in frontal area of 2ME-treated rats, with respect to sham-operated rats (p < 0.01). Furthermore, in parietal area, protein levels of DIO1 in 2ME-treated rats were significantly higher than in sham-operated rats (p < 0.01). Moreover MCT8 and OATP1C1 both resulted significantly higher (p < 0.05 and p < 0.001) in sham frontal cortex. CONCLUSION: In summary, our data on SHRs, while confirming the hypotensive effect of two MEs, show that the treatment also solicits the three deiodinases production in the cerebral cortex.

Modification of cardiac thyroid hormone deiodinases expression in an ischemia/reperfusion rat model after T3 infusion.

The deiodinases regulate the activation and inactivation of Thyroid hormones (TH), in both physiological and pathological conditions. The three deiodinases, DIO1, DIO2 and DIO3, have different catalytic role and cellular and tissue distribution. Aim of this study is to evaluate a rat model of regional ischemia/reperfusion (I/R), the modification of cardiac main function after the administration of 6 µg/kg/day of triiodothyronine (T3), and the associated to DIO1, DIO2 and DIO3 gene expression. We also aim to study DIO1 and DIO2 protein levels in different left ventricular regions after an ischemic event. Four groups of rats were studied: sham-operated, sham-operated + T3, I/R rats and I/R rats + T3. DIO1, DIO2 and DIO3 expression were evaluated in I/R region (AAR: area-at-risk) and in a more distant region from ischemic wound (RZ: remote zone). In I/R group, circulating free-T3 (FT3) levels were significantly decreased with respect to basal values, whereas in I/R + T3 rats, FT3 levels were comparable to basal values. In AAR of I/R + T3 rats, DIO1 and DIO2 gene expression significantly increased with respect to sham. In RZ, DIO1 and DIO3 gene expression was significantly lower in sham and I/R rats when compared to I/R + T3. In sham + T3 group, DIO1 and DIO2 gene expression was not detectable, whereas DIO3 was significantly higher than in the other three groups. The present study gives interesting new insights on DIO1, DIO2 and DIO3 in the ischemic heart and their role in relation to T3-mediated amelioration of cardiac function and structure.