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Background: Protein-coding genes have been considered the functional part of the genome, although they represent only 2% of the genome. In contrast, more than 90% of the genome produces non-coding RNA (ncRNA), including antisense (AS) genes, a type of long non-coding genes (encoding transcripts > 200 nucleotides) located on the opposite strand of coding genes. Therefore, antisense RNA (asRNA) can be complementary to the counterpart sense RNA, supporting a regulatory role with potential pathogenic consequences, as their deregulation has been associated with cardiovascular disease, cancer, and diabetes. Results: We performed an in-depth review of AS genes in Ensembl and evaluated the expression of AS genes in human liver by third-generation RNA sequencing methods. Currently, 1656 AS genes overlapping with 1556 sense genes have been identified in the human genome. Coding genes with antisense counterparts were significantly larger and had higher transcriptional activity than genes without antisense counterparts. RNA nanopore sequencing of 15 human livers identified 185 transcripts (55 novel) from 150 known AS genes, and 1316 transcripts from 807 sense genes, with 111 sense-antisense pairs. Sense transcripts showed higher expression than antisense transcripts. Remarkably, RNA nanopore sequencing of human livers identified 146 transcripts (67 novel) corresponding to 118 possible novel AS genes. Conclusion: This study reveals the landscape of AS genes in the human genome and demonstrates the power of long-read RNA sequencing to identify novel transcripts and even novel AS genes, exploring the relationship between sense and AS gene expression as well. [ABSTRACT FROM AUTHOR]

Serine protease inhibitors (serpins) include thousands of structurally conserved proteins playing key roles in many organisms. Mutations affecting serpins may disturb their conformation, leading to inactive forms. Unfortunately, conformational consequences of serpin mutations are difficult to predict. In this study, we integrate experimental data of patients with mutations affecting one serpin with the predictions obtained by AlphaFold and molecular dynamics. Five SERPINC1 mutations causing antithrombin deficiency, the strongest congenital thrombophilia were selected from a cohort of 350 unrelated patients based on functional, biochemical, and crystallographic evidence supporting a folding defect. AlphaFold gave an accurate prediction for the wild-type structure. However, it also produced native structures for all variants, regardless of complexity or conformational consequences in vivo. Similarly, molecular dynamics of up to 1000 ns at temperatures causing conformational transitions did not show significant changes in the native structure of wild-type and variants. In conclusion, AlphaFold and molecular dynamics force predictions into the native conformation at conditions with experimental evidence supporting a conformational change to other structures. It is necessary to improve predictive strategies for serpins that consider the conformational sensitivity of these molecules. [ABSTRACT FROM AUTHOR]

A detailed understanding of molecular responses to a hypertrophic stimulus in skeletal muscle leads to therapeutic advances aimed at promoting muscle mass. To decode the molecular factors regulating skeletal muscle mass, we utilized a 24-h time course of human muscle biopsies after a bout of resistance exercise. Our findings indicate: (1) the DNA methylome response at 30 min corresponds to upregulated genes at 3 h, (2) a burst of translation- and transcription-initiation factor-coding transcripts occurs between 3 and 8 h, (3) changes to global protein-coding gene expression peaks at 8 h, (4) ribosome-related genes dominate the mRNA landscape between 8 and 24 h, (5) methylation-regulated MYC is a highly influential transcription factor throughout recovery. To test whether MYC is sufficient for hypertrophy, we periodically pulse MYC in skeletal muscle over 4 weeks. Transient MYC increases muscle mass and fiber size in the soleus of adult mice. We present a temporally resolved resource for understanding molecular adaptations to resistance exercise in muscle (http://data.myoanalytics.com) and suggest that controlled MYC doses influence the exercise-related hypertrophic transcriptional landscape. Synopsis: A 24-h time course of recovery after an acute hypertrophic stimulus—resistance exercise—unravels the temporal dynamics of gene expression in healthy untrained human skeletal muscle. MYC's pulsatile pattern after exercise likely facilitates its hypertrophic function in differentiated adult muscle cells. Global protein-coding gene expression changes peak at 8 h after an acute hypertrophic stimulus in human skeletal muscle, and early DNA methylation responses predict later gene expression changes. MYC is a key transcription factor regulating gene expression after resistance exercise, specifically during late recovery (8–24 h). Genetically controlled pulses of Myc in skeletal muscle of mice are sufficient for hypertrophy. A 24-h time course of recovery after an acute hypertrophic stimulus—resistance exercise—unravels the temporal dynamics of gene expression in human skeletal muscle. MYC's pulsatile pattern after exercise likely facilitates its hypertrophic function in differentiated adult muscle cells. [ABSTRACT FROM AUTHOR]

Blasts are a threat both in military and civil contexts due not only to explosive devices but also to gas leakages or other accidents. Numerical models could aid to plan response strategies in the short and long term. Nevertheless, due to modeling complexities, a standardized computational framework has not been established yet. In this challenging context, the present study assesses the prediction of blast‐induced traumas by using the total human model for safety (THUMS) human model, which has never been attempted before to the authors knowledge. The pedestrian model is publicly available, hence the demonstration of its suitability to predict blast injuries could benefit the establishment of a common modeling framework. Therefore, the THUMS human model was exposed to different blast scenarios both in free field and partially confined spaces and the response of vital organs was investigated. Trauma patterns to internal organs of the THUMS were consistent with available experimental data and injury thresholds. In conclusion, THUMS open‐source human model demonstrated its validity to reproduce primary blast‐related injuries, addressing the development of standardization of numerical simulations of human response to explosions. [ABSTRACT FROM AUTHOR]

Circadian rhythms are ∼24 h cycles evident in behaviour, physiology and metabolism. The molecular mechanism directing circadian rhythms is the circadian clock, which is composed of an interactive network of transcription–translation feedback loops. The core clock genes include Bmal1, Clock, Rev‐erbα/β, Per and Cry. In addition to keeping time, the core clock regulates a daily programme of gene expression that is important for overall cell homeostasis. The circadian clock mechanism is present in all cells, including skeletal muscle fibres, and disruption of the muscle clock is associated with changes in muscle phenotype and function. Skeletal muscle atrophy is largely associated with a lower quality of life, frailty and reduced lifespan. Physiological and genetic modification of the core clock mechanism yields immune dysfunction, alters inflammatory factor expression and secretion and is associated with skeletal muscle atrophy in multiple conditions, such as ageing and cancer cachexia. Here, we summarize the possible interplay between the circadian clock modulation of immune cells, systemic inflammatory status and skeletal muscle atrophy in chronic inflammatory conditions. Although there is a clear disruption of circadian clocks in various models of atrophy, the mechanism behind such alterations remains unknown. Understanding the modulatory potential of muscle and immune circadian clocks in inflammation and skeletal muscle health is essential for the development of therapeutic strategies to protect skeletal muscle mass and function of patients with chronic inflammation. [ABSTRACT FROM AUTHOR]

Myotonic dystrophy type 1 (DM1) is caused by mutations in the DMPK gene, and it is associated with cognitive deficits and intelligence below normative values. The objective of this systematic review and meta-analysis was to estimate the overall intelligence and proportion of intellectual development disorder (IDD) in the population with DM1 and its association with its onset. Systematic searches of Medline, Scopus, Web of Science, and Cochrane Library were performed from inception to January 2023. Studies that determined the full intelligence quotient (FIQ) or the IDD proportion in populations with DM1 were included. Meta-analyses of the FIQ and IDD and the FIQ mean difference and IDD prevalence ratios (PRs) by disease onset, inheritance, and genotype were conducted. Forty-five studies were included in the meta-analyses, and all were performed in the DM1 population. The FIQ and IDD in DM1 were 77.90 (71.98, 83.81) and 0.44 (0.27, 0.60), respectively. Furthermore, DM1 onset was negatively associated with intelligence. Thus, the comparison "Congenital versus Adult" onsets resulted in an intelligence quotient of −41.61 (−47.81, −35.40) points and a PR of IDD of 9.49 (3.23, 27.89). Finally, maternal inheritance was also negatively associated, but the genotype did not have a statistically significant association. The alterations in intelligence in DM1 are highly associated with the onset of the disease. However, the genotype did not explain these alterations well and there may be other genetic or epigenetic factors that should be considered. [ABSTRACT FROM AUTHOR]

The explosion of data and its handling has reshaped business priorities and changed conventional decision-making methods. Organisations need to think about how to successfully redesign jobs and ways of working as a fusion, not a compromise, between people and technology to increase the leverage of technology. People and technologies have become intensive collaborators. Analytical thinking is becoming the most sought-after skill, along with creative thinking and other cognitive skills. Openness, flexibility, and agility, along with a high level of motivation and self-awareness, as well as the desire for lifelong learning, are personal characteristics that distinguish a desirable employee. This paper aims to identify the changes that have occurred because of the digitisation of workplaces and the consequent development of skills as the basis of good and quality work. The scientific contribution of this paper is to methodologically explain the changes caused by digitisation and point out the development factors. The methodological paper describes research on the education and investment of human potential skills in a domestic and foreign sample of surveyed Croatian migrants. This research concludes that the respondents believe that everyone individually deserves the most for the development of human potential and that they are not ready to invest in the development of their skills. [ABSTRACT FROM AUTHOR]

A 2‐year‐2‐month‐old, male Syrian hamster (Mesocricetus auratus) was referred for ulceration and encrustation of the abdominal skin. The affected skin was surgically excised. Histological examination revealed changes consistent with an epitheliotropic T‐cell lymphoma. Two months after the surgery, no clinical signs of disease or tumour recurrence were evident. When patients with consistent clinical signs are presented, cutaneous neoplasia should be considered, especially in older animals. Surgical excision may offer short‐term remission for epitheliotropic lymphoma. [ABSTRACT FROM AUTHOR]

Purpose: To create a machine-learning model for estimating the likelihood of post-retrograde intrarenal surgery (RIRS) sepsis. Methods: All consecutive patients with kidney stone(s) only undergoing RIRS in 16 centers were prospectively included (January 2022–August 2023). Inclusion criteria: adult, renal stone(s) only, CT scan (within three months), mid-stream urine culture (within 10 days). Exclusion criteria: concomitant ureteral stone, bilateral procedures. In case of symptomatic infection/asymptomatic bacteriuria, patients were given six days of antibiotics according to susceptibility profiles. All patients had antibiotics prophylaxis. Variables selected for the model: age, gender, age-adjusted Charlson Comorbidity Index, stone volume, indwelling preoperative bladder catheter, urine culture, single/multiple stones, indwelling preoperative stent/nephrostomy, ureteric access sheath, surgical time. Analysis was conducted using Python programming language, with Pandas library and machine learning models implemented using the Scikit-learn library. Machine learning algorithms tested: Decision Tree, Random Forest, Gradient Boosting. Overall performance was accurately estimated by K-Fold cross-validation with three folds. Results: 1552 patients were included. There were 20 (1.3%) sepsis cases, 16 (1.0%) septic shock cases, and three more cases (0.2%) of sepsis-related deaths. Random Forest model showed the best performance (precision = 1.00; recall = 0.86; F1 score = 0.92; accuracy = 0.92). A web-based interface of the predictive model was built and is available at https://emabal.pythonanywhere.com/ Conclusions: Our model can predict post-RIRS sepsis with high accuracy and might facilitate patient selection for day-surgery procedures and identify patients at higher risk of sepsis who deserve extreme attention for prompt identification and treatment. [ABSTRACT FROM AUTHOR]

Background: Osmotic Demyelination Syndrome (ODS) encompasses Central Pontine Myelinolysis and Extrapontine Myelinolysis, both of which are serious neurological conditions linked to the overly rapid correction of hyponatremia. Despite growing evidence, the exact etiology of ODS remains incompletely understood. The present paper describes two case studies, aiming to provide a comprehensive overview of the pathological findings and clinical outcomes associated with ODS. Case presentation: Case #1. A 74-year-old woman was admitted to the emergency department following a head trauma caused by a loss of consciousness. Initial laboratory tests revealed severe hyponatremia (sodium level of 101 mmol/L) and hypokalemia (potassium level of 2.9 mmol/L). The patient underwent corrective therapy with saline and potassium chloride. Despite the correction of electrolyte imbalances, the patient developed a hyperintense lesion in the median portion of the pons on T2-fluid-attenuated inversion recovery (FLAIR) MRI sequence 14 days post-treatment, consistent with ODS. The patient's condition deteriorated, leading to irreversible coma and status epilepticus, culminating in death 32 days after admission. Case #2. An 81-year-old woman with a medical history of hypothyroidism, hypertension, major depression, and stage 3 chronic kidney disease presented with mild gait disturbances. Subsequent testing revealed severe hyponatremia (sodium level of 100 mmol/L). Following an initial clinical improvement due to sodium correction, the patient's condition worsened, with symptoms progressing to confusion, lethargy, and eventually, ODS. Dermatological manifestations, including blistering lesions and facial edema, appeared as the condition advanced. The patient succumbed to irreversible coma 47 days after admission. Conclusion: ODS traditionally carried a poor prognosis, with high mortality rates and diagnoses often made postmortem. However, recent advances in understanding the pathophysiology, along with improvements in diagnostic techniques such as MRI and intensive care treatments, have led to earlier identification, treatment, and recognition of milder forms of the syndrome. Despite these advancements, ODS remains a critical condition with significant risks, particularly following the rapid correction of severe hyponatremia. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is a hallmark of cancer cachexia (CC). Mitochondrial reactive oxygen species (ROS) are elevated in muscle shortly after tumor onset. Targeting mitochondrial ROS may be a viable option to prevent CC. The aim of this study was to evaluate the efficacy of a mitochondria-targeted antioxidant, SkQ1, to mitigate CC in both biological sexes. Male and female Balb/c mice were injected bilaterally with colon 26 adenocarcinoma (C26) cells (total 1 × 106 cells) or PBS (equal volume control). SkQ1 was dissolved in drinking water (∼250 nmol/kg body wt/day) and administered to mice beginning 7 days following tumor induction, whereas control groups consumed normal drinking water. In vivo muscle contractility of dorsiflexors, deuterium oxide-based protein synthesis, mitochondrial respiration and mRNA content of mitochondrial, protein turnover, and calcium channel-related markers were assessed at endpoint (25 days following tumor induction). Two-way ANOVAs, followed by Tukey's post hoc test when interactions were significant (P ≤ 0.05), were performed. SkQ1 attenuated cancer-induced atrophy, promoted protein synthesis, and abated Redd1 and Atrogin induction in gastrocnemius of C26 male mice. In female mice, SkQ1 decreased muscle mass and increased catabolic signaling in the plantaris of tumor-bearing mice, as well as reduced mitochondrial oxygen consumption, regardless of tumor. However, in females, SkQ1 enhanced muscle contractility of the dorsiflexors with concurrent induction of Ryr1, Serca1, and Serca2a in TA. In conclusion, the mitochondria-targeted antioxidant SkQ1 may attenuate CC-induced muscle loss in males, while improving muscle contractile function in tumor-bearing female mice, suggesting sexual dimorphism in the effects of this mitochondrial therapy in CC. NEW & NOTEWORTHY: Herein, we assess the efficacy of the mitochondria-targeted antioxidant SkQ1 to mitigate cancer cachexia (CC) in both biological sexes. We demonstrate that SkQ1 administration attenuates muscle wasting induced by C26 tumors in male, but not female, mice. Conversely, we identify that in females, SkQ1 improves muscle contractility. These phenotypic adaptations to SkQ1 are aligned with respective responses in muscle protein synthesis, mitochondrial respiration, and mRNA content of protein turnover, as well as mitochondrial and calcium handling-related markers. [ABSTRACT FROM AUTHOR]

Background: Vamorolone has recently been approved for the management of Duchenne muscular dystrophy to replace glucocorticosteroids, which theoretically have more side effects. However, its efficacy and safety profile is unclear. Objective: We aimed to assess the efficacy of vamorolone in Duchenne muscular dystrophy through the 6-minute walk test (6MWT), the North Star Ambulatory Assessment (NSAA), time to stand velocity (TTSTAND), time to run 10 m (TTRW), time to climb four stairs (TTCLIMB) and a safety profile. Methods: A systematic search was conducted in MEDLINE, Scopus, Web of Science and the Cochrane Library from inception to June 2024 (PROSPERO: CRD42024558413) for studies evaluating the effect or safety profile of vamorolone in a population with Duchenne muscular dystrophy on 6MWT, NSAA and TTSTAND. TTRW, TTCLIMB and a safety profile were included. The risk of bias was assessed using the Cochrane Collaboration's risk of bias tool (RoB2) and the Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group from the US National Institutes of Health National Heart, Lung, and Blood Institute, depending on the type of design. Results were expressed as mean differences or proportions with 95% confidence intervals (CIs), depending on the outcome. Results: Six studies with a total of 145 individuals with Duchenne muscular dystrophy and a baseline age between 4.7 and 5.5 years were included in the systematic review. Overall, the most effective dose was 6 mg/kg/day. At 24 weeks, this dose showed a statistically significant effect compared with the untreated cohorts of 41.60 m (95% CI 14.30, 68.90) on the 6MWT, 3.57 points (95% CI 1.89, 5.25) on the NSAA, 0.06 events/s (95% CI 0.02, 0.10) on the TTSTAND, approximately 0.25 m/s on the TTRW and 0.04 (95% CI −0.00, 0.08) to 0.07 events/s (95% CI 0.03, 0.11) on the TTCLIMB. There was some discrepancy in the statistical significance of some studies, although the direction of the effect was usually similar. In general, the effect was maintained in the extension studies. Adverse events were less frequent than in historical cohorts treated with glucocorticoids. Finally, the risk of bias in the included studies was low. Conclusions: According to our results, vamorolone offers a statistically and clinically significant benefit in the management of Duchenne muscular dystrophy, with fewer side effects than glucocorticoids. However, the number of studies limits the interpretability and generalisability of these data, requiring more studies with more participants to perform a meta-analysis. [ABSTRACT FROM AUTHOR]

Background: Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous group of skeletal diseases characterized by epiphyseal abnormalities associated with mild short stature. The clinical variability is wide, and the first clinical manifestations still occur in childhood with joint pain and stiffness that evolve into degenerative joint disease. MED, caused by mutations in the Cartilage Oligomeric Matrix Protein (COMP) gene, is the most common form of the disease. COMP-MED usually shows significant involvement of the capital femoral epiphyses and irregular acetabulum; instead, COL9A1-, COL9A2-, and COL9A3-MED appear to have more severe knee involvement than hips, resulting in a milder presentation than COMP-MED cases. Other complications have been reported, in particular osteochondritis dissecans (OCD), which has been described in two large COL9A2-related MED families associated with myopathy. Methods: Here, we report the case of a 24-year-old man affected by COMP-MED with a positive family history for the disease and a clinical presentation that interestingly is characterized by the presence of multiple OCD. Results: To our knowledge, this is the first case of COMP mutations related to multiple OCD as the main clinical feature. Conclusions: This report can expand the clinical phenotype related to the pathogenic variants of the COMP gene, as it shows that multiple OCD can also be present in COMP-related MED as well as in COL9A2-related MED. [ABSTRACT FROM AUTHOR]

Microbial fermentation is a well-known strategy for enhancing the nutraceutical attributes of foods. Among the fermentation outcomes, bioactive peptides (BAPs), short chains of amino acids resulting from proteolytic activity, are emerging as promising components thanks to their bioactivities. Indeed, BAPs offer numerous health benefits, including antimicrobial, antioxidant, antihypertensive, and anti-inflammatory properties. This review focuses on the production of bioactive peptides during the fermentation process, emphasizing how different microbial strains and fermentation conditions influence the quantity and quality of these peptides. Furthermore, it examines the health benefits of BAPs from fermented foods, highlighting their potential in disease prevention and overall health promotion. Additionally, this review addresses the challenges and future directions in this field. This comprehensive overview underscores the promise of fermented foods as sustainable and potent sources of bioactive peptides, with significant implications for developing functional foods and nutraceuticals. [ABSTRACT FROM AUTHOR]

Introduction: Urinary incontinence (UI) is defined as any involuntary loss of urine that causes negative impacts on women's lives. Pelvic floor muscle training (PFMT) is considered to be "level A" of scientific evidence in the treatment of UI. Despite its efficacy, it is known that the effect of PFMT may depend on continuous adherence. Therefore, healthcare professionals are looking for alternatives to improve adherence in their patients. Healthcare has been innovating through mobile device apps. Objective: Thus, the objective of this study was to verify the effects of PFMT with the use of a mobile device app in incontinent women. Trial Design: This was a controlled, randomized clinical trial that occurred remotely. Methods: A total of 104 women with stress UI and/or mixed incontinence, over 18 years old, literate, with preserved cognitive capacity, with internet access and a mobile device with the Android system, participated in this study. They were randomly divided into two groups: The App group and the Booklet group, which underwent a PFMT protocol guided by a mobile app and a booklet, respectively. Both groups received daily reminders to perform the exercises. Before and after 12 weeks of intervention, it was evaluated using the International Consultation on Incontinence Questionnaire‐Short Form (ICIQ‐SF) and the King's Health Questionnaire (KHQ). Results: Both groups showed improvements in the final ICIQ‐SF score. However, superior results were shown for the Booklet group (App: pre: 11.5 [±3.8], post: 9.8 [±4.5]; Booklet: pre: 12.6 [±4.5], post: 7.4 [±4.3]; p = 0.03). Conclusion: It was concluded that PFMT, with the use of a mobile app, is capable of reducing UI and the impact of UI, but it is not superior to training with the use of booklet instructions. [ABSTRACT FROM AUTHOR]

Introduction: Stroke negatively impacts both patients and their families, who must face multiple changes after the onset of the disease. Family caregivers must face new problems with a possible sense of inadequacy, stress and burden. Our retrospective study aimed to assess the burden of caregivers during the rehabilitation process of patients with Stroke. Material and method: This study included patients with a diagnosis of stroke and their caregiver, who attended the Day Hospital of the IRCCS Neurolesi Center "Bonino-Pulejo", Messina, Italy, between January 2018 and October 2019, using electronic recovery system data. The final sample consisted of 30 patients and their caregivers. Results: Significant improvements were observed in patients' cognitive and mood scores, reflecting the efficacy of rehabilitation therapies. Additionally, a correlation emerged between patients' reported anxiety levels and caregivers' reported depression levels, highlighting a dynamic interaction between the emotional states of the two groups. Conclusion: The study highlights the intricate interplay between caregiver characteristics, patient outcomes, and family dynamics in the context of caregiving. Targeted interventions aimed at improving family resilience and coping mechanisms are crucial to optimizing the well-being of both caregivers and patients. [ABSTRACT FROM AUTHOR]

Fat embolism (FE) is a historically recognised but still actively researched topic in forensic pathology. Several aspects remain not fully elucidated, such as its aetiopathogenesis, its causal role in death determination, the impact of interfering factors (e.g. cardiopulmonary resuscitation or other medical procedures) and both qualitative and quantitative diagnostic methodologies in clinical and forensic contexts. These issues are further underscored by the potential involvement of FE in the causal determination of non‐traumatic deaths, which often raises questions of professional liability. The present study aims to provide a comprehensive and up‐to‐date overview of the most recent scientific evidence relevant to forensic pathology. Our systematic research has included 58 articles from 1990 to the present on the topic of FE and fat embolism syndrome (FES). From these articles, we identified 45 case reports, from which the authors’ descriptions were extracted to provide information on individual cases and the operational methods of forensic pathologists. Additionally, 21 experimental studies were identified, and their key findings have been summarised narratively. It has emerged that both traumatic and non‐traumatic cases are frequently reported in the forensic context, with orthopaedic and cosmetic surgery being among the highest‐risk specialities. Experimental studies have re‐evaluated the role of a patent foramen ovale in the pathogenesis of FE, as well as the impact of cardiopulmonary resuscitation in causing FE severe enough to result in death. Additionally, there are new findings regarding diagnostic techniques, including radiological and immunohistological methods; however, they have not yet fully bridged the reliability gap compared to an accurate autopsy–histological evaluation. The major critical points that emerged include the lack of complete and detailed information on premortem clinical conditions, the underutilisation of grading systems and the methodological heterogeneity applied, resulting in considerable variability regarding the organs studied histologically and the diagnostic techniques used. Despite the limitations associated with the analysis of case reports and the heterogeneity of included experimental studies, we believe that this study can provide a comprehensive overview of the FE topic. It furnishes pathologists with an updated overview useful for clinical practice and guiding future research trends, as well as facilitating the development of standardised procedures. [ABSTRACT FROM AUTHOR]

This study explores the effect of praseodymium oxide (PrOx) impregnation in lanthanum nickelate Ruddlesden–Popper (RP) type materials for use in oxygen electrodes of solid oxide cells (SOCs). These mixed conductors are free of cobalt and strontium, which are increasingly being avoided in solid oxide cell applications. We investigate two compositions, La2NiO4+δ (L2N1) and La4Ni3O10−δ (L4N3), demonstrating distinct electrical and oxygen kinetic properties. The L2N1 material exhibits superior performance due to its higher bulk oxygen-ion diffusion, which governs the enhanced ambipolar conduction, crucial for the oxygen exchange process. In the PrOx-impregnated samples, at 700 °C, the total polarization resistance (Rpol) values decrease to ∼0.6 Ω cm2 for L2N1 + PrOx and ∼0.8 Ω cm2 for L4N3 + PrOx, representing reductions by factors of ∼7 and ∼17, respectively, compared to the non-impregnated counterparts. Electrochemical measurements as a function of oxygen partial pressure suggest that surface-exchange processes may be rate-limiting. The impregnated PrOx acts as a catalyst for the dissociative adsorption of oxygen and improves the charge transfer, leading to significant enhancements in the polarization processes. The electrochemical properties and stability of these RP phases in oxidizing conditions, combined with the oxygen transport capabilities and mixed oxidation state of praseodymium oxide (Pr4+/Pr3+), offer promising Co- and Sr-free oxygen electrodes for SOC applications. [ABSTRACT FROM AUTHOR]

Farmed freshwater prawn (Macrobrachium rosenbergii) and black tiger shrimp (Penaeus monodon) comprise a significant portion of Bangladesh's seafood exports, raising concerns about their environmental impacts. Freshwater prawn farms, which require a relatively high amount of feed supply, release 1.0 MT CO2-equivalents/year, equating to 18.8 kg CO2e/MT prawn, contributing significantly to global warming and climate change risks. Integrated Multi-Trophic Aquaculture (IMTA) offers an alternative farming method to conventional prawn farming systems, as it minimizes greenhouse gas (GHG) emissions and climate change impacts. Systematically reviewing 112 scientific articles on IMTA, this article offers recommendations for adopting IMTA to promote sustainable freshwater prawn farming in Bangladesh. IMTA is undergoing extensive experimentation and practice in many parts of the world, offering economic benefits, social acceptability, and environmental sustainability. In addition to native prawn species, various indigenous organic extractive freshwater mollusks, and inorganic extractive plants are available which can seamlessly be used to tailor the IMTA system. Extractive organisms, including aquatic mollusks and plants within prawn farms, can capture blue carbon effectively lowering GHG emissions and helping mitigate climate change impacts. Aquatic mollusks offer feed for fish and livestock, while aquatic plants serve as a dual food source and contribute to compost manure production for crop fields. Research on IMTA in Bangladesh was primarily experimented on finfish in freshwater ponds, with the absence of studies on IMTA in prawn farms. This necessitates conducting research at the prawn farmer level to understand the production of extractive aquatic mollusk and plants alongside prawn in the prawn-producing regions of southwestern Bangladesh. [ABSTRACT FROM AUTHOR]

Introduction: Opioids have been shown to induce neuroinflammation and immune cell activation, that might contribute to some of the opioid side effects, such as opioid-induced tolerance and paradoxical hyperalgesia. In this context, TLR4/MD-2 complex has been proposed as an off-target site for opioid action. This study was aimed at investigating the effect of fentanyl on lipopolysaccharide (LPS)-induced TLR4/MD-2 activation in rat primary microglia and human monocyte-derived macrophages (MDM). Materials and Methods: The effect of fentanyl was first explored by measuring the expression and release of different proinflammatory mediators in primary rat microglia and human MDM by real-time PCR and ELISA. Then, the involvement of TLR4/MD-2 signaling was investigated studying NF-κB activation in HEK293 cells stably transfected with human TLR4, MD-2, and CD14 genes (HEK-Blue hTLR4 cells) and in human MDM. Results: Fentanyl increased mRNA levels, as well as the LPS-induced secretion of proinflammatory mediators in primary microglia and MDM. Two inhibitors of TLR4/MD-2 signaling, namely the oxazoline derivative of N-palmitoylethanolamine (PEA-OXA) and CLI-095, blocked the production and release of proinflammatory cytokines by microglia stimulated with LPS and fentanyl, suggesting that TLR4/MD-2 could be the target of the proinflammatory activity of fentanyl. Finally, we showed that fentanyl in combination with LPS activated NF-κB signaling in human MDM and in HEKBlue hTLR4 cells and this effect was blocked by inhibitors of TLR4/MD-2 complex. Discussion: These results provide new insight into the mechanism of the proinflammatory activity of fentanyl, which involves the activation of TLR4/MD-2 signaling. Our findings might facilitate the development of novel inhibitors of TLR4/MD-2 signaling to combine with opioid-based analgesics for effective and safe pain management. [ABSTRACT FROM AUTHOR]

The need to develop synthetic bone substitutes with structures, properties, and functions similar to bone and capable of preventing microbial infections is still an ongoing challenge. This research is focused on the preparation and characterization of three-dimensional porous scaffolds based on hydroxyapatite (HA)-functionalized calcium carbonate loaded with silver nanoparticles and simvastatin (SIMV). The scaffolds were prepared using the foam replica method, with a polyurethane (PU) sponge as a template, followed by successive polymer removal and sintering. The scaffolds were then coated with poly(lactic-co-glycolic) acid (PLGA) to improve mechanical properties and structural integrity, and loaded with silver nanoparticles and SIMV. The scaffolds were characterized by X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), ATR FT-IR, and silver and SIMV loading. Moreover, the samples were analyzed by Brillouin and Raman microscopy. Finally, in vitro bioactivity, SIMV and silver release, and antimicrobial activity against Staphylococcus aureus and Staphylococcus epidermidis were evaluated. From the Brillouin spectra, samples showed characteristics analogous to those of bone tissue. They exhibited new hydroxyapatite growth, as evidenced by SEM, and good antimicrobial activity against the tested bacteria. In conclusion, the obtained results demonstrate the potential of the scaffolds for application in bone repair. [ABSTRACT FROM AUTHOR]

While school principals are bestowed with executive powers to lead schools, it appears that, among others, gender contributes significantly to the challenges faced by female secondary school principals. This qualitative study explores challenges encountered by female secondary school principals in Lesotho. The study is framed in Critical Theory (CT) as its overarching theoretical framework. CT is concerned with critiquing the gender-ascribed stereotypes that propagate the challenges confronting female secondary school principals. CT is also concerned with advocating for social justice and social reforms. Fifteen (15) female principals were conveniently selected from Lesotho's three geographical regions: lowlands, foothills and highlands. The rationale was to identify any differences ascribed to specific geographical regions, which differ not only in geographical features but also in socio-economic status and traditional values. Semi-structured interviews were used to generate data, and a deductive thematic analysis approach was used to analyse the data. The study revealed that female secondary school principals experience various challenges, some aggravated by the conditions prevalent in the highland areas. The challenges included the teachers' resistance (both males and females) to follow instructions, difficulties in disciplining boys and sexual harassment. The study recommends teacher induction and sensitisation, community sensitisation, and the induction of female principals themselves as possible strategies that could mitigate the challenges faced by female secondary school principals in Lesotho. [ABSTRACT FROM AUTHOR]

Speaking ability is an important skill that must be possessed by students, especially in the field of tourism. This study aims to explore the effect of role play and learning motivation on the speaking ability of first-year students of the Rooms Division at Palembang Tourism Polytechnic. This research method used a factorial design with a population of first-year students of the Hospitality Department. The research sample consisted of 32 participants, consisting of 16 people in the Experiment Group and 16 people in the Control Group. Data were collected through questionnaires and two measurement instruments, then analyzed using Two-Way Analysis of Variance. The results showed that there was a significant effect of role play on students' speaking ability, both those with high and low learning motivation. In addition, conventional teaching techniques also had a significant effect on students' speaking ability, depending on their level of learning motivation. The use of role play proved to be more effective than the conventional teaching technique in improving students' speaking ability. This finding shows that there is an interaction between role play and learning motivation that affects students' speaking ability. Therefore, this finding emphasizes the importance of applying innovative methods and high motivation in the learning process to improve students' speaking ability. The implications of this study suggest that educators prioritize interactive and motivational teaching strategies to improve speaking skills, which are crucial for career readiness in the tourism industry. In addition, role play can be a key component in the curriculum that aims to improve communication skills at various levels of student motivation. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment, characterized by deficits in cognitive functions and loss of delayed and immediate recall, disproportionately affects individuals aged 65 years and older, particularly those with comorbid cardiovascular conditions such as hypertension and diabetes mellitus. Objective: This study aimed to investigate the potential association between intranasal insulin and cognitive and/or memory impairment, with a specific focus on delayed and immediate recall, considering the rising prevalence of cognitive disorders in the aging population. Methodology: Employing a rigorous systematic approach, we conducted a thorough search of MEDLINE, Scopus, the Cochrane database, and Web of Science from inception to November 23, 2022, identifying relevant randomized clinical trials. Our analyses encompassed three key aspects: (i) assessing the impact of intranasal insulin on cognitive impairment, (ii) evaluating its effect on delayed recall, and (iii) examining its influence on immediate recall. Results: Five studies meeting the inclusion criteria were included. The results underscored a statistically significant effect of intranasal insulin on delayed memory (effect size: 1.37; 95% CI: 0.65 to 2.09) and overall cognition (effect size: 0.58; 95% CI: 0.08 to 1.08). However, no statistically significant effect was observed for immediate memory (effect size: 0.48; 95% CI: -0.00 to 0.96). Conclusions: This study provides compelling evidence supporting the significance and efficacy of intranasal insulin in enhancing delayed recall and overall cognition. The observed effects hold promise for potential therapeutic interventions in addressing cognitive deficits associated with aging and comorbid conditions. The findings emphasize the need for further research to elucidate the underlying mechanisms and optimize the application of intranasal insulin in cognitive enhancement strategies. [ABSTRACT FROM AUTHOR]

Mechanosensing and mechanotransduction pathways between the Extracellular Matrix (ECM) and cells form the essential crosstalk that regulates cell homeostasis, tissue development, morphology, maintenance, and function. Understanding these mechanisms involves creating an appropriate cell support that elicits signals to guide cellular functions. In this context, polymers can serve as ideal molecules for producing biomaterials designed to mimic the characteristics of the ECM, thereby triggering responsive mechanisms that closely resemble those induced by a natural physiological system. The generated specific stimuli depend on the different natural or synthetic origins of the polymers, the chemical composition, the assembly structure, and the physical and surface properties of biomaterials. This review discusses the most widely used polymers and their customization to develop biomaterials with tailored properties. It examines how the characteristics of biomaterials-based polymers can be harnessed to replicate the functions of biological cells, making them suitable for biomedical and biotechnological applications. [ABSTRACT FROM AUTHOR]

Background/Objectives: Urinary tract infections (UTIs) are infections that involve the urethra, bladder, and, in much more severe cases, even kidneys. These infections represent one of the most common diseases worldwide. Various pathogens are responsible for this condition, the most common being Escherichia coli (E. coli). Bromelain is a proteolytic complex obtained from the stem and stalk of Ananas comosus (L.) Merr. showing several beneficial activities. In addition to bromelain, N-acetylcysteine (NAC) has also been used. Methods: The purpose of this experiment was to evaluate the antibacterial, anti-motility, and anti-biofilm effects of a new polyenzymatic complex (DIF17BRO®) in combination with NAC (the Formulation) on various strains of E. coli isolated from patients with UTIs. Subsequently, the anti-inflammatory and antioxidant effects of the Formulation were studied in an ex vivo model of cystitis, using bladder samples from mice exposed to E. coli lipopolysaccharide (LPS). Results: Our results showed that the Formulation significantly affects the capability of bacteria to form biofilm and reduces the bacteria amount in the mature biofilm. Moreover, it combines the interesting properties of NAC and a polyenzyme plant complex based on bromelain in a right dose to affect the E. coli adhesion capability. Finally, the Formulation exhibited protective effects, as confirmed by the inhibitory activities on multiple inflammatory and oxidative stress-related pathways on bladder specimens exposed to LPS. Conclusions: This blend of active compounds could represent a promising and versatile approach to use to overcome the limitations associated with conventional therapies. [ABSTRACT FROM AUTHOR]

Checkpoint inhibitors (ICIs) have demonstrated substantial efficacy in the treatment of numerous solid tumors, including head and neck cancer. Their inclusion in the therapeutic paradigm in metastatic lines of treatment has certainly improved the outcomes of these patients. Starting from this assumption, numerous studies have been conducted on ICIs in other earlier disease settings, including studies conducted in patients in neoadjuvant settings. However, how many and which studies are truly significant? Can they lay concrete foundations for further future studies and therefore allow us to continue to have this interesting future perspective? Through a review of the existing literature, coupled with insights gleaned from clinical practice and from the main recently published studies, we aim to examine the therapeutic potential of ICIs in patients affected by head and neck cancer in a neoadjuvant treatment setting and encourage researchers to set up successful future clinical trials. [ABSTRACT FROM AUTHOR]

Pathogenic variants in the transcription factor TP63 are associated with clinically overlapping syndromes including ectrodactyly-ectodermal dysplasia clefting (EEC) and ankyloblepharon-ectodermal defects-cleft lip/palate (AEC). T cell lymphopenia has rarely been described in individuals with TP63 variants and the cause of the T cell defect is unclear. Here, we present a case of a female infant born with TP63-related syndrome and profound T cell lymphopenia, first uncovered through newborn screening. Flow cytometry analysis revealed low CD4+ naïve T cells and nearly absent CD8+ T cells with intact B and NK cell compartments. A de novo heterozygous pathogenic variant c.1040 G>A (C347Y) in exon 8 of TP63 was identified. An artificial thymic organoid system, to assess the intrinsic ability of the patient's hematopoietic cells to develop into T cells, was performed twice using separate peripheral blood samples. Ex vivo T cell differentiation was evident with the artificial organoid system, suggesting that a thymic stromal cell defect may be the cause of the T cell lymphopenia. Consistent with this, interrogation of publicly available data indicated that TP63 expression in the human thymus is restricted to thymic epithelial cells. Based on these data, congenital athymia was suspected and the patient received an allogenic cultured thymus tissue implant (CTTI). This is the first report of suspected congenital athymia and attempted treatment with CTTI associated with TP63 variant. At 9 months post-implant, peripheral lymphocyte analysis revealed measurable T cell receptor excision circles and presence of CD4+ recent thymic emigrants suggestive of early thymopoiesis. She will continue regular monitoring to ensure restoration of T cell immunity. [ABSTRACT FROM AUTHOR]

Children and adolescents with Intellectual Disability (ID) experience a worse Quality-of-Life (QoL) relative to typically developing peers. Thus, QoL evaluation is important for identifying support needs and improving rehabilitation effectiveness. Nevertheless, currently in Italy there are not tools with this scope. This study aims to translate and cross-culturally adapt the Quality-of-Life Inventory-Disability (QI-Disability) into Italian. The process consisted in forward-backward translation, cross-cultural adaptation and cognitive debriefing. Eventually, QI-Disability was conceptually and semantically equivalent to the original one. A validation study is necessary to make the tool available in Italian clinical practice and educational contexts to improve these children's QoL. [ABSTRACT FROM AUTHOR]

Breast milk is the natural source of nutrition for infants, but while it supports their health, it can also be a potential source of toxic inorganic particulate matter, and this applies to both breast milk and industrially produced milk. The aim of the present study was to evaluate the presence of nanoparticles in both breast milk and formula milk samples. We collected and analyzed, via a new electron scanning microscopic procedure, 19 samples of breast milk from Italian women and 19 formula milk samples produced by different companies. Organic–inorganic agglomerates were detected in 58% of formula and in 63% of breast milk samples, respectively. In addition, a significantly (p < 0.05) greater size of nanoparticles was observed in formula milk samples. The results, showing the presence of inorganic nanosized particles in breast and artificial milk, may lead to future studies aimed at investigating possible nanosized contamination of milk and identifying early prevention strategies for women and animals involved in the food chain. [ABSTRACT FROM AUTHOR]

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Background: Reliable Human Papillomavirus (HPV) testing and genotyping are essential for quality assurance in HPV-based primary screening, disease management and for monitoring the impact of HPV vaccination. The clinical validation of HPV molecular diagnostic assays has significantly contributed to these objectives; however, little emphasis has been placed on assuring sample quality. This study aimed to evaluate the accuracy of sample cellularity assessment using the C-C Motif Chemokine Receptor 5 (CCR5) gene target as a marker of sample adequacy in molecular diagnostics. Methods: Jurkat cell line samples were counted using both a Thoma cell-counting chamber and Fluorescence-Activated Cell Sorting (FACS). Jurkat cell line samples at three different concentrations were subsequently evaluated using the OncoPredict HPV Quality Control (QC) real-time PCR assay, employing CCR5 for molecular cellularity quantification. Results: The cellularity values obtained were comparable across the three different methods for all dilutions of the cell line tested. Conclusions: The results obtained from this study show that CCR5 represents a promising molecular marker for the accurate quantification of sample cellularity, confirming its use as a reliable sample adequacy control, thus reducing the risk of "false-negative" results. [ABSTRACT FROM AUTHOR]

This review covers recent advancements in the use of zirconium phosphates and phosphonates (ZrPs) as catalysts or catalyst supports for a variety of reactions, including biomass conversion, acid–base catalysis, hydrogenation, oxidation, and C-C coupling reactions, from 2015 to the present. The discussion emphasizes the intrinsic catalytic properties of ZrPs, focusing on how surface acidity, hydrophobic/hydrophilic balance, textural properties, and particle morphology influence their catalytic performance across various reactions. Additionally, this review thoroughly examines the use of ZrPs as supports for catalytic species, ranging from organometallic complexes and metal ions to noble metals and metal oxide nanoparticles. In these applications, ZrPs not only enhance the dispersion and stabilization of active catalytic species but also facilitate their recovery and reuse due to their robust immobilization on the solid support. This dual functionality underscores the importance of ZrPs in promoting efficient, selective, and sustainable catalytic processes, making them essential to the advancement of green chemistry. [ABSTRACT FROM AUTHOR]

• Chronic mild stress induces anhedonia in 50 % of female rats. • Stress vulnerability is associated with increased immune and inflammatory markers. • Lurasidone treatment reverses anhedonia and normalizes immune-inflammatory markers. Stress exposure is a key risk factor for the development of depressive-like conditions. However, despite the higher incidence of Major Depressive Disorder in the female population, classical stress-based experimental paradigms have primarily focused on males. In the present study, we used the well-established chronic mild stress (CMS) paradigm to investigate the development of anhedonia, a cardinal symptom of affective disorders, in the female animals and we also studied the potential effect of the antipsychotic drug lurasidone in normalizing the alterations brought about by stress exposure. We found that three weeks of CMS exposure produced a significant reduction of sucrose intake in 50% of the animals (vulnerable, CMS-V), whereas the others were resilient (CMS-R). The development of an anhedonic phenotype in CMS-V was associated with a significant elevation of different immune markers, such as Complement C3 and C4, and inflammatory cytokines, including INFß and Il1ß in dorsal and ventral hippocampus. Interestingly, sub-chronic treatment with the antipsychotic drug lurasidone was able to revert the anhedonic phenotype while normalizing most of the molecular alterations found in rats vulnerable to CMS exposure. This study extends the ability of lurasidone to normalize the anhedonic phenotype in CMS rats also to females. Moreover, we provide novel evidence on lurasidone's potential effectiveness in treating mental disorders characterized by immune-inflammatory dysfunction. [ABSTRACT FROM AUTHOR]

Background: Low birth weight (LBW) has been established as a major determinant of neonatal mortality and morbidity. However, there is no evidence of the effectiveness of different types of physical exercise (PE) at different intensities during pregnancy to prevent LBW. Objectives: To compare the effectiveness of different types of PE at different levels of intensity in pregnant women to prevent LBW. Design: A systematic review and network meta-analysis was performed according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols for Network Meta-Analysis extension statement. Data Sources and Methods: We searched the PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science databases from inception to November 2023. We included randomized controlled trials (RCTs). A random effects method was used to calculate the pooled mean difference (MD). The effect of each intervention was calculated using a network meta-analysis with a frequentist perspective. Results: Forty-three RCTs were included in the systematic review, and 38 RCTs were included in the network meta-analysis. In the general population, although no significant results, the MDs for light-moderate strength, moderate-vigorous strength, and moderate-vigorous Pilates exercises were favorable for preventing LBW. Furthermore, moderate-vigorous strength exercise was effective to prevent LBW, reporting significant MD compared to control groups in the healthy population (310.00, 95% confidence interval: 78.40, 541.60; I 2 = 81.3%). Conclusion: Strength exercises at a moderate-vigorous intensity could be a potential strategy for the prevention of LBW in the healthy population. However, our findings should be interpreted with caution because the overall risk of bias was between "some concerns" and "high," and the overall certainty of the evidence was low. Registration: PROSPERO CRD42023401770. [ABSTRACT FROM AUTHOR]

Intercalation compounds represent a unique class of materials that can be anisotropic (1D and 2D-based topology) or isotropic (3D) through their guest/host superlattice repetitive organisation. Intercalation refers to the reversible introduction of guest species with variable natures into a crystalline host lattice. Different host lattice structures have been used for the preparation of intercalation compounds, and many examples are produced by exploiting the flexibility and the ability of 2D-based hosts to accommodate different guest species, ranging from ions to complex molecules. This reaction is then carried out to allow systematic control and fine tuning of the final properties of the derived compounds, thus allowing them to be used for various applications. This review mainly focuses on the recent applications of intercalation layered compounds (ILCs) based on layered clays, zirconium phosphates, layered double hydroxides and graphene as heterogeneous catalysts, for environmental and health purposes, aiming at collecting and discussing how intercalation processes can be exploited for the selected applications. [ABSTRACT FROM AUTHOR]

Herein, initially, we present a general overview of the global financial support for chemistry devoted to materials science, specifically intercalation layered compounds (ILCs). Subsequently, the strategies to synthesise these host structures and the corresponding guest-host hybrid assemblies are exemplified on the basis of some families of materials, including pillared clays (PILCs), porous clay heterostructures (PCHs), zirconium phosphate (ZrP), layered double hydroxides (LDHs), graphite intercalation compounds (GICs), graphene-based materials, and MXenes. Additionally, a non-exhaustive survey on their possible application in the field of energy through electrochemical storage, mostly as electrode materials but also as electrolyte additives, is presented, including lithium technologies based on lithium ion batteries (LIBs), and beyond LiBs with a focus on possible alternatives such XIBs (X = Na (NIB), K (KIB), Al (AIB), Zn (ZIB), and Cl (CIB)), reversible Mg batteries (RMBs), dual-ion batteries (DIBs), Zn-air and Zn-sulphur batteries and supercapacitors as well as their relevance in other fields related to (opto)electronics. This selective panorama should help readers better understand the reason why ILCs are expected to meet the challenge of tomorrow as electrode materials. [ABSTRACT FROM AUTHOR]

Objectives: This systematic review aimed to analyse the published evidence for the use of non-invasive methods for the early detection of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). Methods: The literature was systematically searched through several databases: PubMed, Cochrane Library, and Web of Science. Additional exploration was performed through cross-checks on the bibliographies of selected reviews. The inclusion criteria involved studies assessing the application of non-invasive tests on humans in the screening, diagnosis, or surveillance of OSCC or OPMDs and reporting sensitivity (SE) and specificity (SP). The Newcastle–Ottawa scale (NOS) was applied to assess the quality of the studies included. Results: The search strategy resulted in 8012 preliminary records. After a duplicate check, 116 titles remained. After abstract analysis, 70 papers remained. After full text analysis, only 54 of the 70 papers fit the inclusion criteria (28 were original articles and 26 were reviews). Those 26 reviews were used to manually search for further original articles. From this last search, 33 original articles were found. Thus, a total of 61 original studies were included and investigated. Findings from this systematic review indicate useful information, such as a description of the mechanisms, ease of use, limitations, and SE and SP values, to drive the choice of the optimal minimally invasive method to be utilized as an adjunctive tool to examine the suspicious lesions. Conclusions: Each of the analysed tools can be improved or implemented, considering their high SE and low SP. Despite advancements, incisional biopsy continues to be the gold standard for the definitive diagnosis of oral cancer and precancerous lesions. Further research and development are essential to improving the sensitivity, specificity, and reliability of non-invasive tools for widespread clinical application. [ABSTRACT FROM AUTHOR]