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Abstract Background Ageing is associated with an increased risk of lung infection and chronic inflammatory lung disease. Innate immune responses are the first line of defence in the respiratory tract, however, age-related changes to innate immunity in the lung are not fully described. Both resident haematopoietic cells, such as alveolar macrophages, and non-haematopoeitic cells, such as epithelial and endothelial cells can contribute to inflammatory and immune responses in the lung. In this study we aimed to determine the impact of ageing on early innate responses of resident cells in the lung. Results Aged and young mice were inoculated intranasally with lipopolysaccharide (LPS). After 4 h, aged mice recruited higher numbers of neutrophils to the airways and lung. This exacerbated inflammatory response was associated with higher concentrations of chemokines CXCL1, CXCL2 and CCL2 in the airways. Next, precision cut lung slices (PCLS) were stimulated ex vivo with LPS for 16 h. Gene expression of Cxcl2, Tnf and Il1b were all higher in PCLS from aged than young mice and higher levels of secretion of CXCL2 and TNF were detected. To determine which lung cells were altered by age, LPS was intranasally administered to aged and young mice and individual populations of cells isolated by FACS. RT-PCR on sorted cell populations demonstrated higher expression of inflammatory cytokines Cxcl2, Ccl2 and Tnf in epithelial cells and alveolar macrophages and higher expression of Cxcl2 by endothelial cells of aged mice compared to young. These differences in expression of pro-inflammatory cytokines did not correspond to higher levels of Tlr4 expression. Conclusions Ageing leads to a heightened neutrophilic inflammatory response in the lung after LPS exposure, and higher expression and production of pro-inflammatory cytokines by resident lung cells, including alveolar macrophages, epithelial cells and endothelial cells. The responses of multiple resident lung cell populations are altered by aging and contribute to the exacerbated inflammation in the lung following LPS challenge. This has implications for our understanding of respiratory infections and inflammation in older people.

Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory coronavirus-2 (SARS-CoV-2). Several explanations for the development of cardiovascular complications during and after acute COVID-19 infection have been hypothesized. The COVID-19 pandemic, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. The myocardial injury in COVID-19 patients has been associated with coronary spasm, microthrombi formation, plaque rupture, hypoxic injury, or cytokine storm, which have the same pathophysiology as the three clinical variants of Kounis syndrome. The angiotensin-converting enzyme 2 (ACE2), renin-aldosterone system (RAAS), and kinin-kallikrein system are the main proposed mechanisms contributing to cardiovascular complications with the COVID-19 infection. ACE receptors can be found in the heart, blood vessels, endothelium, lungs, intestines, testes, neurons, and other human body parts. SARS-CoV-2 directly invades the endothelial cells with ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This causes angiotensin II accumulation downregulation of the ACE2 receptors, resulting in prothrombotic effects, such as hemostatic imbalance via activation of the coagulation cascade, impaired fibrinolysis, thrombin generation, vasoconstriction, endothelial and platelet activation, and pro-inflammatory cytokine release. The KKS system typically causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation, but SARS-CoV-2 infection impairs such counterbalancing effects. This cascade results in cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries, microvascular disease, Kounis syndrome, prolonged COVID, myocardial fibrosis, myocarditis, new-onset hypertension, pericarditis, postural orthostatic tachycardia syndrome, pulmonary hypertension, stroke, Takotsubo syndrome, venous thromboembolism, and thrombocytopenia. In this narrative review, we describe and elucidate when, where, and how COVID-19 affects the human cardiovascular system in various parts of the human body that are vulnerable in every patient category, including children and athletes.

Background Primary Health Care (PHC) was the cornerstone of the pandemic response.Objectives We aimed to explore the positive and negative impact of the pandemic, during its final wave, through ‘PHC providers’ eyes’, as well as their recommendations towards restructuring and enhancing PHC services.Methods A two-phase qualitative study was conducted, pursuing data triangulation from Focus Groups (FGs) and individual, semi-structured interviews for the purposes of data completeness and confirmation (summer 2022 and spring 2023, respectively). A purposive sample of settings was employed, including in total five PHC units according to location with different population distribution; one in Athens (FGs) and four in Northern Greece (interviews). Inductive content analysis was used.Results In total, 24 PHC professionals participated in FGs, whereas 17 were individually interviewed. Our findings reflect a general understanding of the pandemic’s positive imprint, namely acceleration of digitalisation, establishment of health protection measures, recognition of PHC’s role, raise in public awareness of primary prevention, team-cooperation, increase in providers’ self-efficacy, appointment of health professionals and re-organisation of accessibility. The negative impact is summarised in fatigue/burnout in PHC providers, patient safety concerns and changes in patients’ behaviour. To increase resilience, participants suggest restructuring PHC, recruiting PHC personnel and enhancing digital infrastructure, maintenance of sanitary protection measures, investment in quality, and empowering patients through health literacy.Conclusion Based on the lessons learnt, building further on the pandemic-accelerated digitalisation, emphasising on quality improvement and patient safety, ensuring providers’ well-being, and empowering citizens through health literacy could be key in promoting PHC resilience.

Thyrotropin (TSH) suppression is required in the management of patients with papillary thyroid carcinoma (PTC) to improve their outcomes, inevitably causing iatrogenic thyrotoxicosis. Nevertheless, the evidence supporting this practice remains limited and weak, and in vitro studies examining the mitogenic effects of TSH in cancerous cells used supraphysiological doses of bovine TSH, which produced conflicting results. Our study explores, for the first time, the impact of human recombinant thyrotropin (rh-TSH) on human PTC cell lines (K1 and TPC-1) that were transformed to overexpress the thyrotropin receptor (TSHR). The cells were treated with escalating doses of rh-TSH under various conditions, such as the presence or absence of insulin. The expression levels of TSHR and thyroglobulin (Tg) were determined, and subsequently, the proliferation and migration of both transformed and non-transformed cells were assessed. Under the conditions employed, rh-TSH was not adequate to induce either the proliferation or the migration rate of the cells, while Tg expression was increased. Our experiments indicate that clinically relevant concentrations of rh-TSH cannot induce proliferation and migration in PTC cell lines, even after the overexpression of TSHR. Further research is warranted to dissect the underlying molecular mechanisms, and these results could translate into better management of treatment for PTC patients.

In recent years, the health-promoting properties of plant-derived compounds have garnered increasing scientific interest. Notably, tomatoes and pumpkins (Cucurbita moschata), renowned for their abundant phytochemicals and associated biological activities, have become focal points of research. This study investigated the extraction of phenolic compounds from tomatoes and pumpkins cultivated on Lemnos, an Aegean Island, aiming to enhance the nutritional profiles of food products. We established an extraction protocol for total phenolics and evaluated the antioxidant capacity using response surface methodology. Utilizing a central composite design, we optimized the extraction parameters, with time and ethanol concentration identified as critical factors (p < 0.05). The optimized extracts demonstrated substantial phenolic content (9.47 ± 0.08 and 4.52 ± 0.05 mg GAE/g for tomatoes and pumpkins, respectively) and antioxidant capabilities as determined by DPPH (7.65 ± 0.08 and 5.78 ± 0.05 μmol TE/g, respectively), ABTS (9.27 ± 0.02 and 3.95 ± 0.04 μmol TE/g, respectively), FRAP (5.25 ± 0.09 and 2.99 ± 0.03 μmol TE/g, respectively), and CUPRAC assays (2.3 ± 0.04 and 1.25 ± 0.03 μmol TE/g, respectively). Following extraction, the phenolic compounds were encapsulated using maltodextrin and subsequently freeze-dried, yielding high encapsulation efficiency. In alignment with a comprehensive strategy aimed at fostering functional snacks that enhance local economic and public health outcomes, vegetables sourced from local farms were employed to develop a savory cereal bar enriched with tomato extract and a sweet cookie infused with pumpkin extract.

Several studies and research papers have been published to elucidate and understand the mechanism of the coronavirus disease 2019 (COVID-19) pandemic and its long-term effects on the human body. COVID-19 affects a number of organs, including the female reproductive system. However, less attention has been given to the effects of COVID-19 on the female reproductive system due to their low morbidity. The results of studies investigating the relationship between COVID-19 infection and ovarian function in women of reproductive age have shown the harmless involvement of COVID-19 infection. Several studies have reported the involvement of COVID-19 infection in oocyte quality, ovarian function, and dysfunctions in the uterine endometrium and the menstrual cycle. The findings of these studies indicate that COVID-19 infection negatively affects the follicular microenvironment and dysregulate ovarian function. Although the COVID-19 pandemic and female reproductive health have been studied in humans and animals, very few studies have examined how COVID-19 affects the female reproductive system. The objective of this review is to summarize the current literature and categorize the effects of COVID-19 on the female reproductive system, including the ovaries, uterus, and hormonal profiles. The effects on oocyte maturation, oxidative stress, which causes chromosomal instability and apoptosis in ovaries, in vitro fertilization cycle, high-quality embryos, premature ovarian insufficiency, ovarian vein thrombosis, hypercoagulable state, women’s menstrual cycle, the hypothalamus-pituitary-ovary axis, and sex hormones, including estrogen, progesterone, and the anti-Müllerian hormone, are discussed in particular.

Ionic liquids have been described as green solvents, however, their presence in the aquatic environment may indicate a threat for key species. Focusing on the freshwater ecosystem, five ionic liquids containing the 1‑butyl‑3-methylimidazolium (BMIM) cation were compared for their acute toxicity and chronic responses on daphnids. Biochemical markers of physiology including the activity of phosphatases, β-galactosidase, peptidase, lipase and glutathione-S-transferase were used to assess changes in physiology of daphnids. Feeding and reproduction were investigated as surrogate phenotypic measures. Feeding rate was decreased in all exposures, and severely impacted in BMIM hexafluorophosphate, chloride, and tetrafluoroborate, while reproduction was unaffected by all ionic liquids. A diverse set of responses were triggered from each BMIM ionic liquid in reference to enzyme activities providing insight for the toxicity impact of these emerging contaminants. Phosphatase activities were significantly decreased in all exposure scenarios to ionic liquids, but different patterns of biochemical responses were documented among acute and chronic exposures and different ionic liquids, indicating distinct mechanistic patterns. The aforementioned results highlight the toxic potential of ionic liquids which are characterised so far as green solvents.

Thalassaemia International Federation (TIF), representing the united voice of people with thalassaemia and their families globally, has been striving for more than three decades to empower research, by academic communities and industry, to focus on developing a safe and effective curative approach for thalassaemia. Such a cure would lead to new lives with equal opportunities and challenges, as for every other person not suffering from a severe chronic disease. A gene therapy product was finally authorised in May 2019 by the European Medicinal Agency, thus marking a milestone in the history of the disease. However, after this conditional authorization, everyone focused on numbers and opted for cost of illness and cost-effectiveness studies, inadmissibly ignoring patients’ voices and needs. The product was finally withdrawn from Europe, despite the fact that all implicated stakeholders, including governments, academia and industry always knew that an innovative and complex therapy would be expensive but always supported and fought for its development. In this article, TIF expresses its view on this issue, including some thoughts on how to address the high cost of innovative therapies.

Nutrition and calorie intake are associated with subtle changes of thyroid function tests in subjects with an intact Hypothalamic-Pituitary-Thyroid axis. Iodine deficiency and extreme fluctuations in calorie intake, such as those that occur during periods of starvation or overfeeding could lead to alterations in thyroid hormones. The dietary macronutrient and micronutrient composition could also influence the thyroid function. Recently, Low-Glycemic Load (LGL) diets have become very popular and are effective in the treatment and/or prevention of several medical conditions, including diabetes, obesity, cardiovascular disease, and epilepsy. In this review, we report on the available data from the literature regarding the association between LGL diets and thyroid function or dysfunction. Several studies conducted in this field to date have yielded inconsistent results.

Background and Objectives: Specificity and reliability issues of the current cortisol assessment methods lead to limitations on the accurate assessment of relative adrenal insufficiency. Although free cortisol provides a more accurate evaluation of adrenal cortisol production, the expense and time-consuming nature of these assays make them impractical for routine use. Research has, thus, focused on alternative methods, such as indirectly measuring free cortisol using Coolens’ equation or directly assessing salivary cortisol concentration, which is considered a more favorable approach despite associated challenges like sampling issues and infection risks. The aim of this study was to explore correlations between 24 h urinary free cortisol (UFC), free plasma cortisol, serum total cortisol, and salivary cortisol as potential reliable indices of free cortisol in the setting of variceal bleeding. Additionally, we assessed the predictive value of UFC for 6-week mortality and 5-day treatment failure in patients with liver cirrhosis and variceal bleeding. Materials and Methods: A total of 40 outpatients with liver cirrhosis and variceal bleeding were enrolled. Free cortisol levels in serum, saliva, and urine were assessed using the electrochemiluminescence immunoassay method. For the measurement of plasma-free cortisol, a single quadrupole mass spectrometer was employed. The quantification of free cortisol was fulfilled by analyzing the signal response in the negative ESI-MS mode. Results: UFC was significantly correlated to free plasma cortisol. Negative correlations were demonstrated between UFC, the Child–Pugh (CP) score, and C reactive protein (CRP) levels. In the multivariate analysis, CP stage C was associated with 6-week mortality risk and portal vein thrombosis with 5-day treatment failure using Cox regression and binary logistic regression analyses, respectively. Patients who experienced rebleeding, infection, or death (or any combination of these events) presented with lower levels of UFC. Conclusions: This study suggests that low levels of UFC may impose a risk factor for patients with liver cirrhosis and variceal bleeding. The use of UFC as an index of adrenal cortisol production in variceal bleeding warrants further investigation.

Antioxidants are known to play a crucial role in maintaining cellular health by neutralizing harmful free radicals. Among various dietary sources of antioxidants, wheat-based products, particularly flours, have gained significant attention due to their potential health benefits. Durum wheat, a widely cultivated species, serves as a primary ingredient in numerous food products. However, limited research has been conducted to assess the antioxidant activity of flours obtained from durum wheat varieties. In this study, we aimed to comparatively evaluate the antioxidant and antiplatelet potential of flours from 22 selected durum wheat varieties cultivated in Greece. We focused on three major parameters for antioxidant activity measurement: total phenolic content, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and ferric-reducing antioxidant power (FRAP). The total phenolic content was determined using the Folin–Ciocalteu method, while DPPH and FRAP assays were employed to assess the ability of flours to scavenge free radicals and reduce ferric ions, respectively. The antiplatelet activity was evaluated using a platelet-activating factor inhibition assay (PAF) in platelet-rich plasma. Analysis of the data revealed notable differences in the total phenolics and antioxidant and antiplatelet activities among the tested samples. The total phenolic content ranged from 624.0 ± 3.5 to 950.0 ± 5.3 μg of gallic acid equivalent/g flour with the variety Zeta E having the highest content. The antioxidant activities based on the DPPH and FRAP assays ranged from 0.56 ± 0.02 to 2.26 ± 0.08 and 1.93 ± 0.02 to 3.65 ± 0.03 μmol of Trolox equivalent/g flour, respectively, with the varieties Marco Aurelio and Zeta E exerting the highest antioxidant activities in the DPPH and FRAP tests, respectively. In addition, the IC50 values for the antiplatelet activity ranged from 0.72 ± 0.21 to 3.06 ± 0.17 in mg of flour, with the variety of Zoi exhibiting the highest antiplatelet activity. Overall, this comparative evaluation highlights the differences in the antioxidant and antiplatelet activities among flours obtained from 22 different durum wheat varieties cultivated in Greece. The results from this study aid in the selection of wheat varieties with superior antioxidant and antiplatelet capacities for use in bakery food formulation and dietary recommendations.

COVID-19, a contagious disease caused by the novel coronavirus SARS-CoV-2, emerged in 2019 and quickly became a pandemic, infecting more than 700 million people worldwide. The disease incidence, morbidity and mortality rates have started to decline since the development of effective vaccines against the virus and the widespread immunization of the population. SARS-CoV-2 vaccines are associated with minor local or systemic adverse reactions, while serious adverse effects are rare. Thyroid-related disorders have been reported after vaccination for COVID-19, and Graves’ disease (GD) is the second most common amongst them. Thyroid eye disease (TED), an extrathyroidal manifestation of GD, is rarely observed post-COVID-19 vaccination. All TED cases followed mRNA-based vaccinations, but two new onset mild TED cases post-viral vector vaccine (ChAdox1nCoV-19) have also been reported. We report the case of a 63-year-old woman who presented with new onset hyperthyroidism and moderate-to-severe and active TED 10 days after she received the first dose of a viral vector vaccine against SARS-CoV-2. This is the first case of moderate-to-severe TED after such a vaccine. Our patient was initially treated with intravenous glucocorticoids, and subsequently with intravenous rituximab, due to no response. The disease was rendered inactive after rituximab, but constant diplopia persisted, and the patient was referred for rehabilitative surgery.

Frustrated by her students' glib use of catch-all terms such as 'militarism' in addressing causation, Alexia Michalaki wanted her Year 9 students to produce mature causal explanations of World War I. To encourage this to happen she went back into decades of pedagogical writing and research, teasing out the ways in which others have sought to improve students' causal understanding and finding her own path. Michalaki explains and analyses her means of getting students to approach causation through the narrative which underlies the big organising concepts, and makes a cogent case for Year 9 going more deeply than they sometimes do into the chronological and geographical background of World War I.

IntroductionThe nature of thyroid nodules is heterogenous. Most of them are benign and, in the absence of pressure symptoms of adjunct structures, no treatment is needed. Our objective was to investigate the acute effects of a low dose of recombinant human TSH (rhTSH) on the volume of benign thyroid nodules.Methodswe studied 27 nodules (14 isoechoic and 13 hypoechoic) in 15 (11 women and 4 men; mean age: 51.0 ± 15.9 years) consecutive patients with one to three well-separated asymptomatic benign thyroid nodules. All subjects were euthyroid, with negative thyroid antibodies, and none received levothyroxine. The total thyroid volume and thyroid nodule volume were sonographically determined by two independent examiners (P.B. and M.M.) before, 48 hours and 6 months post intramuscular (IM) administration of 0.3mg rhTSH, and the mean values of the two examiners’ measurements were used; thyroid function tests were obtained at the same time points.ResultsThe mean volume of isoechoic nodules increased by 57.3%, of hypoechoic nodules by 46.6% and of the surrounding thyroid parenchyma by 70.4% 48 hours post-rhTSH; mean volumes had returned to baseline levels 6 months later. A large variance in the volume change responses was observed. The relative change in nodule volume (defined as the percent change in nodule volume divided by the percent change in the surrounding parenchyma) from baseline to 48 hours was significantly higher in isoechoic versus hypoechoic nodules (p

Simple Summary: Serum TSH suppression in the management of PTC patients will inevitably cause iatrogenic thyrotoxicosis. Our study challenges, for the first time, the role of human recombinant thyrotropin (rh-TSH) as a mitogen on PTC cell lines. For this study, both K1 and TPC-1 cells were treated with clinically relevant rh-TSH under various conditions. The expression levels of TSHR and thyroglobulin (Tg) were determined and, subsequently, the proliferation and migration were assessed. Additionally, cells were engineered to overexpress TSHR in order to multiply TSH signal transduction. Under the conditions employed, rh-TSH was inadequate for inducing either the proliferation or the migration rate of both transformed and non-transformed cells, while Tg expression was increased. We report that, clinically speaking, rh-TSH doses cannot induce proliferation and migration in PTC cell lines, thus questioning TSH suppression in PTC patients. Further research is warranted to dissect the underlying mechanisms. These results could translate into better PTC patient management. Thyrotropin (TSH) suppression is required in the management of patients with papillary thyroid carcinoma (PTC) to improve their outcomes, inevitably causing iatrogenic thyrotoxicosis. Nevertheless, the evidence supporting this practice remains limited and weak, and in vitro studies examining the mitogenic effects of TSH in cancerous cells used supraphysiological doses of bovine TSH, which produced conflicting results. Our study explores, for the first time, the impact of human recombinant thyrotropin (rh-TSH) on human PTC cell lines (K1 and TPC-1) that were transformed to overexpress the thyrotropin receptor (TSHR). The cells were treated with escalating doses of rh-TSH under various conditions, such as the presence or absence of insulin. The expression levels of TSHR and thyroglobulin (Tg) were determined, and subsequently, the proliferation and migration of both transformed and non-transformed cells were assessed. Under the conditions employed, rh-TSH was not adequate to induce either the proliferation or the migration rate of the cells, while Tg expression was increased. Our experiments indicate that clinically relevant concentrations of rh-TSH cannot induce proliferation and migration in PTC cell lines, even after the overexpression of TSHR. Further research is warranted to dissect the underlying molecular mechanisms, and these results could translate into better management of treatment for PTC patients. [ABSTRACT FROM AUTHOR]

In recent years, the health-promoting properties of plant-derived compounds have garnered increasing scientific interest. Notably, tomatoes and pumpkins (Cucurbita moschata), renowned for their abundant phytochemicals and associated biological activities, have become focal points of research. This study investigated the extraction of phenolic compounds from tomatoes and pumpkins cultivated on Lemnos, an Aegean Island, aiming to enhance the nutritional profiles of food products. We established an extraction protocol for total phenolics and evaluated the antioxidant capacity using response surface methodology. Utilizing a central composite design, we optimized the extraction parameters, with time and ethanol concentration identified as critical factors (p < 0.05). The optimized extracts demonstrated substantial phenolic content (9.47 ± 0.08 and 4.52 ± 0.05 mg GAE/g for tomatoes and pumpkins, respectively) and antioxidant capabilities as determined by DPPH (7.65 ± 0.08 and 5.78 ± 0.05 μmol TE/g, respectively), ABTS (9.27 ± 0.02 and 3.95 ± 0.04 μmol TE/g, respectively), FRAP (5.25 ± 0.09 and 2.99 ± 0.03 μmol TE/g, respectively), and CUPRAC assays (2.3 ± 0.04 and 1.25 ± 0.03 μmol TE/g, respectively). Following extraction, the phenolic compounds were encapsulated using maltodextrin and subsequently freeze-dried, yielding high encapsulation efficiency. In alignment with a comprehensive strategy aimed at fostering functional snacks that enhance local economic and public health outcomes, vegetables sourced from local farms were employed to develop a savory cereal bar enriched with tomato extract and a sweet cookie infused with pumpkin extract. [ABSTRACT FROM AUTHOR]

Background: Periodic Limb Movements during Sleep (PLMS) have been described to be frequently present in stroke patients. We aimed to evaluate the prevalence and severity of PLMS in acute stroke patients and clarify the association between PLMS and coexisting Sleep Disordered Breathing (SDB). Additionally, we focused on identifying variables that could independently predict the presence of PLMS in patients with acute stroke. The potential impact of PLMS on stroke outcome at three months was investigated as well. Methods: In this study, we performed overnight polysomnography on consecutive stroke patients within 72 h from symptom onset. Data regarding clinical and imaging characteristics were prospectively collected. National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Epworth-Sleepiness Scale (ESS) were used to evaluate stroke severity on admission, stroke outcome at three months and history of daytime sleepiness, respectively. We documented PLMS and SDB using standard polysomnography criteria. Results: We prospectively assessed 126 patients with acute stroke [109 with ischemic and 17 with hemorrhagic stroke, mean age 60 ± 11 years, 68% men, median NIHSS score on admission: 3 (IQR: 2–7)]. The overall rate of PLMS in our cohort was 76%, and the rate of SDB among patients with PLMS was 83%. PLMS detection rates differed significantly (p-value: p-value: 0.001) predict the presence of PLMS in the acute stroke phase in multivariable analyses adjusting for potential confounders. Moreover, baseline stroke severity (NIHSS-score increase in per-1 point: OR: 0.819, 95% CI: 0.737–0.895, p-value < 0.001) and PLMS (OR:0.099, 95% CI: 0.009–0.482, p-value = 0.015) were significantly associated with the likelihood of excellent functional outcome (mRS-scores: 0–1) at 3 months. Conclusion: The common presence of mostly severe PLMS in patients with acute stroke and their negative effect on stroke outcomes point out the necessity for early PLMS detection and treatment.

Beta-thalassemia and particularly its transfusion-dependent form (TDT) is a demanding clinical condition, requiring life-long care and follow-up, ideally in specialized centers and by multidisciplinary teams of experts. Despite the significant progress in TDT diagnosis and treatment over the past decades that has dramatically improved patients’ prognosis, its management remains challenging. On one hand, diagnostic and therapeutic advances are not equally applied to all patients across the world, particularly in several high-prevalence eastern regions. On the other, healthcare systems in low-prevalence western countries that have recently received large numbers of migrant thalassemia patients, were not ready to address patients’ special needs. Thalassaemia International Federation (TIF), a global patient-driven umbrella federation with 232 member-associations in 62 countries, strives for equal access to quality care for all patients suffering from thalassemia or other hemoglobinopathies in every part of the world by promoting education, research, awareness, and advocacy. One of TIF’s main actions is the development and dissemination of clinical practice guidelines for the management of these patients. In 2021, the fourth edition of TIF’s guidelines for the management of TDT was published. The full text provides detailed information on the management of TDT patients and the clinical presentation, pathophysiology, diagnostic approach, and treatment of disease complications or other clinical entities that may occur in these patients, while also covering relevant psychosocial and organizational issues. The present document is a summary of the 2021 TIF guidelines for TDT that focuses mainly on clinical practice issues and recommendations.

Medicinal and herbal plants are abundant sources of phytochemicals, which are biologically active compounds with potential health benefits. The characterisation of phytochemicals has been the subject of many studies, but there is a lack of comprehensive assays to accurately assess the main phytochemical categories and their antioxidant properties. To address this, the present study has developed a multiparametric protocol comprising eight biochemical assays, which quantify the major categories of phytochemicals, including polyphenols, tannins and flavonoids, as well as their antioxidant and scavenging potential. The presented protocol offers several advantages over other methods, including higher sensitivity and significantly lower cost, making it a simpler and more affordable approach compared to commercial kits. The protocol was tested on two datasets with seventeen distinct herbal and medicinal plants, and the results demonstrated its effectiveness in accurately characterising the phytochemical composition of plant samples. The modular design of the protocol allows its adaptation to any spectrophotometric instrumentation, while all assays are simple to follow and require a minimum number of analytical steps.

Pharmaceuticals pose a great threat to organisms inhabiting the aquatic environment. Non-steroidal anti-inflammatory drugs (NSAIDs) are major pharmaceutical pollutants with a significant presence in freshwater ecosystems. In this study, the impact of indomethacin and ibuprofen, two of the most commonly prescribed NSAIDs, was assessed on Daphnia magna. Toxicity was assessed as the immobilization of animals and used to determine non-lethal exposure concentrations. Feeding was assessed as a phenotypic endpoint and key enzymes were used as molecular endpoints of physiology. Feeding was decreased in mixture exposures for five-day-old daphnids and neonates. Furthermore, animals were exposed to NSAIDs and their mixture in chronic and transgenerational scenarios revealing changes in key enzyme activities. Alkaline and acid phosphatases, lipase, peptidase, β-galactosidase, and glutathione-S-transferase were shown to have significant changes in the first generation at the first and third week of exposure, and these were enhanced in the second generation. On the other hand, the third recovery generation did not exhibit these changes, and animals were able to recover from the induced changes and revert back to the control levels. Overall, our study points towards transgenerational exposures as more impactful laboratory studies to understand pharmaceutical stressors with a combination of molecular and phenotypic markers of physiology.

Oregano is native to the Mediterranean region and it has been reported to contain several phenolic compounds particularly flavonoids that have been related with multiple bioactivities towards certain diseases. Oregano is cultivated in the island of Lemnos where the climate promotes its growth and thus it could be further used in promoting local economy. The aim of the present study was to establish a methodology for the extraction of total phenolic content along with the antioxidant capacity of oregano by using response surface methodology. A Box–Behnken design was applied to optimize the extraction conditions with regard to the extraction time, temperature, and solvent mixture with the use of ultrasound-assisted extraction. For the optimized extracts, identification of the most abundant flavonoids (luteolin, kaempferol, and apigenin) was performed with an analytical HPLC-PDA and UPLC-Q-TOF MS methodology. The predicted optimal conditions of the statistical model were identified, and the predicted values confirmed. The linear factors evaluated, temperature, time, and ethanol concentration, all showed significant effect (p < 0.05), and the regression coefficient (R2) presented a good correlation between predicted and experimental data. Actual values under optimum conditions were 362.1 ± 1.8 and 108.6 ± 0.9 mg/g dry oregano with regard to total phenolic content and antioxidant activity based on 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay, respectively. Additionally, further antioxidant activities by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) (115.2 ± 1.2 mg/g dry oregano), Ferric Reducing Antioxidant Power (FRAP) (13.7 ± 0.8 mg/g dry oregano), and Cupric Reducing Antioxidant Capacity (CUPRAC) (1.2 ± 0.2 mg/g dry oregano) assays were performed for the optimized extract. The extract acquired under the optimum conditions contain an adequate quantity of phenolic compounds that could be used in the production of functional foods by food enrichment procedure.

Petroselinum crispum is native to the Mediterranean region and has been reported to contain several phenolic compounds in addition to the highest quantity of apigenin among several natural raw materials. The aim of the present study was to establish an extraction method for the most abundant phenolic compounds of Petroselinum crispum leaves by using response surface methodology. A Box–Behnken design was applied to optimize the extraction conditions with regards to the extraction time, temperature, solvent mixture, and sample to solvent ratio with the use of ultrasound-assisted extraction. An analytical HPLC-PDA methodology was developed to accurately quantify the phenolic compounds in the extracts. Identification of the most abundant phenolic compounds (luteolin, caffeic acid, and apigenin) was also performed with an UPLC-Q-TOF MS methodology. The predicted optimal conditions of the statistical model were identified, and the predicted values confirmed. Actual values of 23.92 ± 1.86 with 100 mL/g, 40% ethanol, 70 °C and 40 min, 19.10 ± 0.75 with 20 mL/g, 0% ethanol, 70 °C and 40 min, and 25.29 ± 1.82 μg/g dry parsley with and 100 mL/g, 0% ethanol, 25 °C and 40 min of luteolin, caffeic acid, and apigenin respectively, were estimated. Total phenolic content and antioxidant activities by DPPH, ABTS, FRAP, and CUPRAC assays were performed for the extracts. The extracts acquired under the optimum conditions contain an adequate quantity of phenolic compounds that could be used in the production of functional foods by food enrichment prcedure.

The article presents a study which investigated the role of pulmonary natural killer T cells (NKT) populations in IPF by analyzing bronchoalveolar lavage (BAL) fluid from patients with idiopathic pulmonary fibrosis (IPF) and healthy control subjects by quantitative polymerase chain reaction (PCR) and flow cytometry. Topics discussed include clinical characteristics of IPF, how the role of NKT cells was ascertained, and how the severity of lung lesions was graded.

The continuous global increase in population and consumption of resources due to human activities has had a significant impact on the environment. Therefore, assessment of environmental exposure to toxic chemicals as well as their impact on biological systems is of significant importance. Freshwater systems are currently under threat and monitored; however, current methods for pollution assessment can neither provide mechanistic insight nor predict adverse effects from complex pollution. Using daphnids as a bioindicator, we assessed the impact in acute exposures of eight individual chemicals and specifically two metals, four pharmaceuticals, a pesticide and a stimulant, and their composite mixture combining phenotypic, biochemical and metabolic markers of physiology. Toxicity levels were in the same order of magnitude and significantly enhanced in the composite mixture. Results from individual chemicals showed distinct biochemical responses for key enzyme activities such as phosphatases, lipase, peptidase, β-galactosidase and glutathione-S-transferase. Following this, a more realistic mixture scenario was assessed with the aforementioned enzyme markers and a metabolomic approach. A clear dose-dependent effect for the composite mixture was validated with enzyme markers of physiology, and the metabolomic analysis verified the effects observed, thus providing a sensitive metrics in metabolite perturbations. Our study highlights that sensitive enzyme markers can be used in advance on the design of metabolic and holistic assays to guide the selection of chemicals and the trajectory of the study, while providing mechanistic insight. In the future this could prove to become a useful tool for understanding and predicting freshwater pollution.

Summary: Macrophage activation results in the accumulation of endogenous metabolites capable of adopting immunomodulatory roles; one such bioactive metabolite is itaconate. After macrophage stimulation, the TCA-cycle intermediate cis-aconitate is converted to itaconate (by aconitate decarboxylase-1, ACOD1) in the mitochondrial matrix. Recent studies have highlighted the potential of targeting itaconate as a therapeutic strategy for lung diseases such as asthma, idiopathic pulmonary fibrosis (IPF), and respiratory infections. This review aims to bring together evidence which highlights a role for itaconate in chronic lung diseases (such as asthma and pulmonary fibrosis) and respiratory infections (such as SARS-CoV-2, influenza and Mycobacterium tuberculosis infection). A better understanding of the role of itaconate in lung disease could pave the way for novel therapeutic interventions and improve patient outcomes in respiratory disorders. Recent studies have highlighted the potential of targeting itaconate as a therapeutic strategy for lung diseases such as asthma, idiopathic pulmonary fibrosis (IPF), and respiratory infections. This short review aims to bring together evidence which highlights a role for itaconate in chronic lung disease. A better understanding of the role of itaconate in respiratory disorders could pave the way for novel therapeutic interventions. [ABSTRACT FROM AUTHOR]